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24 May 2023

Exploring the Potential of Nanotechnology in Pediatric Healthcare: Advances, Challenges, and Future Directions

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College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, USA
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Pharmaceutics2023, 15(6), 1583;https://doi.org/10.3390/pharmaceutics15061583
This article belongs to the Special Issue Paediatric Dosage Forms: New Approaches to Old Challenges
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Abstract

The utilization of nanotechnology has brought about notable advancements in the field of pediatric medicine, providing novel approaches for drug delivery, disease diagnosis, and tissue engineering. Nanotechnology involves the manipulation of materials at the nanoscale, resulting in improved drug effectiveness and decreased toxicity. Numerous nanosystems, including nanoparticles, nanocapsules, and nanotubes, have been explored for their therapeutic potential in addressing pediatric diseases such as HIV, leukemia, and neuroblastoma. Nanotechnology has also shown promise in enhancing disease diagnosis accuracy, drug availability, and overcoming the blood–brain barrier obstacle in treating medulloblastoma. It is important to acknowledge that while nanotechnology offers significant opportunities, there are inherent risks and limitations associated with the use of nanoparticles. This review provides a comprehensive summary of the existing literature on nanotechnology in pediatric medicine, highlighting its potential to revolutionize pediatric healthcare while also recognizing the challenges and limitations that need to be addressed.

1. Introduction

In the field of pediatric oncology, nanotechnology has emerged as a tool with significant potential to advance cancer treatment. It provides several advantages, including targeted drug delivery, reduced toxicity, and combined immunotherapy. These features offer promising benefits in the treatment of specific pediatric tumors such as neuroblastoma, retinoblastoma, CNS tumors, and musculoskeletal tumors [1,2]. Nanotechnology-based approaches, including tailored nanocarriers and liposomes, have shown promise in targeted drug delivery with reduced toxicity for pediatric cancers such as acute lymphoblastic leukemia (ALL) and acute myeloid leukemia [3,4,5,6]. Nanovesicles, peptide-functionalized liposomes, and tumor vascular-targeting liposomes have demonstrated effectiveness in neuroblastoma treatment [7,8]. Furthermore, nanomedicines, nanoparticle-based drug delivery systems, and nanotechnological-based miRNA interventions hold promise for addressing neuroblastoma [9,10,11,12,13,14]. Nanotechnology also shows potential in improving outcomes for osteosarcoma treatment through alpha-particle therapy, exosome mimetics, nanocarriers, and targeted drug delivery systems [15,16,17,18,19,20,21,22].
Nanotechnology extends its potential beyond cancer treatment, as it holds promise in pediatric infectious disease management. Nanomedicines enable targeted drug delivery for malaria treatment and leishmaniasis, reducing toxicity while maintaining efficacy [23,24,25]. Nanoparticles have been utilized in bioassays for detecting and controlling schistosomiasis [26]. Additionally, nanocarriers combat antibiotic resistance and enhance the performance of drugs in infectious diseases [27,28]. Nanofabricated biosensors show high sensitivity in detecting bacterial infections, contributing to innovative approaches in combatting pediatric infectious diseases [29]. Furthermore, nanotechnology has contributed in the diagnosis and treatment of tuberculosis (TB) and human immunodeficiency virus (HIV) infections, improving targeted drug delivery, diagnostics, and treatment outcomes [30,31,32,33,34,35,36,37,38,39].
Respiratory and pulmonary diseases also benefit from nanotechnology advancements. Nanoparticle-based technologies have demonstrated effectiveness in preventing biofilm formation and infection in ventilator-associated pneumonia (VAP) [40,41]. Nanotherapeutic approaches show potential in detecting and treating Respiratory Syncytial Virus (RSV) [42,43]. Nanotechnology has improved diagnostic methods for cystic fibrosis and offered pain management solutions [44,45]. These advancements offer opportunities to enhance disease diagnosis, treatment, and patient outcomes in respiratory and pulmonary diseases.
Nanotechnology plays a vital role in addressing critical issues in pediatric environmental health and infectious diseases. It has proven effective in detecting water-borne parasites and pathogens, providing solutions for public health challenges [46,47,48,49]. Nanotechnology offers potential strategies for addressing scorpion envenomation and controlling viral infections [50,51,52]. Coordinated efforts are needed to leverage nanotechnology’s potential in improving public health outcomes and addressing environmental health issues.
In the field of pediatric medicine, nanotechnology offers innovative solutions for the diagnosis and treatment of various conditions. It has shown promise in epilepsy, expanded newborn screening, cardiovascular diseases, neuroinflammation, neurodegenerative diseases, gestational diabetes, bone disorders, mosquito-borne diseases, micronutrient deficiency, vulvovaginitis, and more [53,54,55,56,57,58,59,60,61,62,63,64]. Nanotechnology holds potential for tissue engineering, personalized nanomedicine, scoliosis, respiratory tract disorders, neurosensory diseases, and infections [65,66,67,68,69,70,71,72,73,74,75,76,77].
The impact of nanotechnology extends to various branches of pediatric medicine. In pediatric dentistry, nanotechnology offers promising solutions, particularly in the treatment of occlusal cavities. Nanoparticles incorporated into resin coatings improve wear resistance, prolonging the lifespan of dental restorations [78]. Nanovectors delivering resveratrol oral sprays reduce plaque formation and inflammation, promoting oral health [79]. Furthermore, polysaccharide-based systems offer biocompatibility and drug delivery potential, enhancing treatment outcomes in pediatric dental care [80]. The incorporation of silver nanoparticles in dental sealants creates antibacterial and rechargeable sealants, preventing the onset of dental caries [81]. Additionally, biodegradable magnesium-alloy stents effectively manage pediatric airway obstruction, providing a promising solution for respiratory conditions [82]. While the benefits of nanotechnology in pediatric dentistry are evident, further research is needed to fully understand its benefits and drawbacks [83].
Pediatric dermatology also benefits from the application of nanotechnology, particularly in the management of atopic dermatitis. Nanocarriers improve drug delivery by enhancing solubility and skin permeation, reducing side effects associated with topical treatments [84]. Chitosan nanoparticles, for instance, enhance drug penetration, leading to improved therapeutic outcomes in atopic dermatitis [85,86]. Additionally, polydopamine nanoparticles have shown the ability to inhibit fibrosis in neonatal scleredema, providing new avenues for the treatment of this condition [87]. Nanotechnological carriers hold promise for improving the efficacy and safety of treatments for various pediatric skin disorders, addressing a significant unmet need in pediatric dermatology [84].
Another crucial area where nanotechnology holds potential is pediatric nutrition. It offers innovative solutions for addressing critical issues such as obesity, nutritional deficiencies, and food allergies in pediatric populations [88]. Nanotechnology-based food production can provide more nutritious and low-calorie options, contributing to improved pediatric dietary habits [89]. Furthermore, iron solid lipid nanoparticles offer an alternative to conventional iron supplements, enhancing the bioavailability of this essential nutrient [90]. Nanotechnology-based optical biosensors enhance food safety by enabling the rapid and accurate detection of harmful contaminants [91]. Additionally, nanotechnology-based diagnostics aid in personalized allergen immunotherapy, ensuring safer and more effective management of food allergies in children [92]. Collaborative efforts are crucial for advancing research and ensuring the safety and efficacy of nanotechnology in the field of pediatric nutrition [88].
One area where nanotechnology has made significant contributions is pediatric drug delivery. It has addressed key challenges such as solubility, taste, and stability, improving the effectiveness of drug therapies in children. Biomimetic nanovesicles incorporated into transdermal patches have been developed to enhance the delivery of micronutrients [93]. In situ self-assembly nanoparticles improve the oral delivery of solid dosage forms, increasing drug bioavailability and therapeutic efficacy [94,95]. Folic acid magnetic nanotheranostics have been developed to reduce cardiotoxicity and enhance targeted drug delivery [96]. Nanoparticle-based systems offer ease of administration and enhanced drug delivery across various routes [97]. Nanofibers and nanocapsules provide effective drug delivery approaches, improving the therapeutic outcomes of pediatric medications [98,99,100]. Nanopatch technology offers a needle-free and painless approach to vaccine delivery—particularly relevant for pediatric immunization [101]. Nanocosmeceuticals benefit from nanoformulations, enabling targeted delivery of skincare ingredients [102].
The integration of nanotechnology in pediatric medicine has ushered in a new era of possibilities. However, it is essential to acknowledge that, along with its tremendous potential, nanotechnology also raises concerns regarding potential health risks. Researchers have highlighted the impact of engineered nanoparticles on children’s health, emphasizing the need for thorough investigations into their safety profiles [103]. Studies have specifically examined the neurotoxicity of nanoparticles, shedding light on the importance of understanding their potential risks [104,105]. Carbon nanoparticles and ultrafine particles are areas that require further exploration to determine their impact on pediatric health [106,107,108].
It is crucial to approach nanotechnology with a cautious and responsible mindset. The unique properties of nanoparticles offer biomedical possibilities, but their safe and responsible use must be prioritized [108]. Public understanding of nanotechnology is also paramount, as it empowers individuals to make informed decisions and fosters trust in its applications. Education and awareness campaigns should be implemented to disseminate accurate information about nanotechnology, addressing both its potential benefits and risks. This paper aims to provide an overview of the advances in nanosystems and their potential applications in major pediatric disorders.

1.1. Pediatric Diseases

The pediatric population, i.e., children, are at high risk of various diseases and disorders such as malaria [109], iron deficiency [110], traumatic brain injury [111], pediatric cancer [112], respiratory syncytial virus [113], and inflammatory bowel disease [114], to name a few. Malaria is a parasitic disease that affects many children in developing countries, while iron deficiency anemia can lead to fatigue, weakness, and developmental delays. Traumatic brain injury is a significant cause of cognitive, emotional, and behavioral problems, and pediatric cancer can be challenging to treat in children. Respiratory syncytial virus can cause severe respiratory illness in infants and young children, and inflammatory bowel disease causes chronic inflammation in the digestive tract, leading to abdominal pain and diarrhea [113,114].
Other diseases and disorders that affect children include dental biofilm and gingival inflammation, vulvovaginitis, diffuse intrinsic pontine gliomas, neuroblastoma, acute myeloid leukemia, HIV, osteosarcoma chemotherapy, craniosynostosis, retinoblastoma, hereditary angioedema, epilepsy, neurodegenerative diseases, asthma, and liver diseases such as biliary atresia and hepatitis. Vaccines are essential for preventing infectious diseases and protecting the health of children, and routine childhood immunization schedules include vaccines against various diseases such as measles, mumps, rubella, and polio. Effective management and early diagnosis of these diseases are crucial for improving quality of life among children and reducing morbidity and mortality.

1.2. Nanosystems

Nanomedicines, a specific class of nanocarriers, have significantly advanced the field of medicine by allowing the targeted and efficient delivery of drugs, imaging agents, and genes to specific cells or tissues in the body [115]. Liposomes and polymeric nanoparticles are examples of nanocarriers that can encapsulate drugs and release them in response to specific triggers, offering controlled and targeted drug delivery [116]. Mesoporous silica nanoparticles, with their high surface area and pore volume, are well-suited for drug delivery, imaging, and biosensing applications [117]. Gold nanoparticles and iron oxide nanoparticles have also been employed for targeted drug delivery and imaging purposes [118]. Biodegradable and CO2-derivative cationic polymeric nanoparticles are emerging as promising nanocarriers in drug delivery due to their biocompatibility, biodegradability, and the ease with which their surface charge can be modified for efficient cellular uptake and targeted drug delivery. Lipid-based nanoparticles, such as solid lipid nanoparticles and nanostructured lipid carriers, possess unique properties that make them ideal for drug delivery and imaging applications. Composite scaffolds, which combine nanoparticles with natural or synthetic polymers, have found applications in tissue engineering and regenerative medicine, enabling the repair and regeneration of damaged tissues and organs [119]. Magnetic nanotheranostics are gaining prominence in the detection and treatment of various diseases, including cancer, cardiovascular diseases, and neurodegenerative diseases [120]. The nanopatch is a novel nanocarrier designed for transdermal drug delivery, providing a painless and convenient alternative to traditional injections [121]. Graphene and its derivatives, such as graphene oxide and reduced graphene oxide, possess unique mechanical, electrical, and optical properties that make them suitable for diverse biomedical applications, including drug delivery, imaging, and biosensing [122].

2. Pediatric Cancer Treatment and Research

2.1. Pediatric Cancers in General

Considerable advancements have been achieved in pediatric oncology, and nanotechnology has emerged as a valuable asset in the fight against cancer. The application of customized nanocarriers for drug delivery has demonstrated promising advantages when treating certain pediatric tumors such as neuroblastoma, retinoblastoma, CNS tumors, and musculoskeletal tumors [1]. Another notable advancement is the use of liposomes as delivery vehicles for anticancer agents in pediatric cancer treatment. This approach has demonstrated improved treatment efficacy while reducing toxic side effects [2].
Nanotechnology-based strategies offer substantial potential for enhancing clinical outcomes in pediatric oncology. These strategies aim to reduce toxicity, achieve targeted delivery, and combine with immunotherapeutic agents. Furthermore, nanotechnology holds promise in various areas, such as prevention, diagnosis, and treatment, encompassing tumor targeting and controlled release [123]. However, the field faces a significant challenge due to the limited availability of nanomedicines for pediatric cancer care [124].
Innovative nanotechnology-based approaches show promise in treating pediatric cancers such as diffuse midline gliomas [125], leukemia [126], osteosarcoma [127], and brain cancers [128]. Nanoparticle-based delivery systems have been found to inhibit tumor cell proliferation and migration in cholesteatoma and pediatric brain tumor cells [129,130]. Nanotechnology-based drug delivery enables the specific targeting of anticancer agents to leukemic cells, thereby reducing toxic side effects [131]. The development of nanotechnology has the potential to improve therapeutic efficiency, drug targeting, reduce toxicity, and mask the bitter taste of drugs, with anticancer drugs being the most frequently encountered therapeutic drug class [132].
For the molecular diagnosis of pediatric sarcomas, NanoString technology has proven to be a reliable approach. It can detect sarcoma-specific fusion transcripts in a single reaction with 100% concordance to RT-PCR [133]. In the proteomic analysis of pediatric ependymoma using high-resolution mass spectrometry, similarities with other pediatric brain tumor entities, such as astrocytomas and medulloblastomas, have been revealed [134]. Table 1 summarizes examples of nanocarrier systems utilized in pediatric medicine.
Table 1. Nanosystems in general pediatric cancer medicine.
Nanotechnology has shown significant potential in addressing pediatric cancer [135]. Ongoing research in this field is expected to yield innovative and effective treatments for these devastating diseases. Figure 1 illustrates the utilization of two strategies employing gold nanoparticles for delivering doxorubicin (DOX) to gliomas. These strategies involve using Agiopeptide-2 as a targeting polymer and poly(ethylene glycol) (PEG) to evade immune recognition.
Figure 1. (A) Elucidation of the An-PEG-DOX-AuNPs. (B) Elucidation of the delivery procedure of An-PEG-DOX-AuNPs. LRP1 receptor could mediate An-PEG-DOX-AuNPs and allow them to penetrate through BBB and target glioma cells, then DOX would be released at the tumor site or in tumor cells and enter into the nuclei to induce tumor cell apoptosis. Printed with permission from [136].

2.2. Leukemia

Numerous studies have investigated the application of nanotechnology in various types of pediatric leukemia, yielding encouraging results. For instance, the use of CHGNPs (carbon-encapsulated hollow gold nanoparticles) has been shown to selectively induce G1 cell cycle arrest by up-regulating the tumor suppressor protein P27. This advancement provides a cytotoxic drug for the clinical treatment of leukemia [3]. However, the efficacy of lipid-based cubosomal nanoformulations in treating Acute Lymphoblastic Leukemia (ALL) in children has yet to be established. This emphasizes the need for cautious consideration when utilizing nanotechnology to enhance drug efficacy [141].
Gold nanoparticle-based nanocarriers for antileukemic drugs have demonstrated potential in drug delivery, cancer diagnosis, and therapy for ALL. A comprehensive overview of conventional methods and nano-strategies for ALL treatment has highlighted the special focus on gold nanoparticle-based nanocarriers [4]. Similarly, polypeptide-based nanoparticles have shown promising outcomes in depleting CD22DeltaE12 through SiRNA-mediated treatment in B-cell Precursor Lymphoblastic Leukemia [5]. Furthermore, poly(lactide-co-glycolide) (PLGA) nanomedicines loaded with 6-mercaptopurine (6-MP) have exhibited enhanced oral bioavailability and tissue distribution. This has resulted in improved in vitro cytotoxicity of Jurkat cells and prolonged survival time in ALL model mice, offering a promising delivery strategy for clinical translation [142]. The Nessler method, employing ultraviolet-visible spectrophotometry, enables the quantification of PEGylated asparaginase activity in plasma for personalized nanomedicine in clinical settings [143]. Moreover, NanoString nCounter technology has demonstrated robust and cost-effective potential for the diagnosis of B-cell acute lymphoblastic leukemia, boasting high sensitivity and specificity [144].
Polymeric nanoparticles loaded with dexamethasone have been found to enhance therapeutic efficacy, leading to improved quality of life and survival in childhood leukemia [145]. Lastly, the use of siRNA-loaded lipid nanoparticles for LNP-si-LINC01257 treatment has proven to be a safe and effective therapeutic approach for pediatric acute myeloid leukemia [6]. While it is crucial to exercise caution when leveraging nanotechnology to enhance drug efficacy, the potential benefits are evident. The continued exploration and utilization of nanotechnology in the treatment of pediatric cancer holds promise for significant advancements in the field. Table 2 summarizes examples of nanocarrier systems utilized in leukemia treatment.
Table 2. Nanosystems in pediatric Leukemia treatment.

2.3. Neuroblastoma

One highly promising development involves the utilization of nanovesicles coated with GASNGINAYLC peptide [7]. In vitro experiments have revealed that these nanovesicles exhibit exceptional biocompatibility and stability, making them a promising tool for actively targeted nanotherapy in the case of neuroblastoma. Additionally, studies have shown that peptide-functionalized liposomes hold great promise in enhancing tumor-homing properties, inducing tumor apoptosis, and reducing tumor glucose consumption. These unique properties make liposomal nanocarriers a valuable tool for multitargeted treatment of neuroblastoma [8].
Furthermore, recent studies have showcased the development of tumor vascular-targeting liposomes, which allow for the targeted release of drugs. This approach has been successfully tested in mice, demonstrating positive results. Figure 2 visually presents the development of these liposomes and illustrates their release characteristics in mice.
Figure 2. Development of doxorubicin-loaded, tumor vascular-targeting liposomes. (A) Schematic representation of the NGR-containing peptide GNGRGGVRSSSRTPSDKYC (called GNGRGC)-targeted, doxorubicin-loaded stealth liposomes (NGR-SL[DXR]). In order to enable coupling of NGR-containing peptide to SL, a cysteine residue (C) was added to the peptide C-terminus. (B,C) Pharmacokinetic profiles and tumor accumulation of NGR-SL[DXR] in NB-bearing mice. Adapted with permission from [8].
These advancements in nanotechnology offer a potential avenue for the development of effective treatments for pediatric cancer, including neuroblastoma. The use of targeted nanocarriers and liposomes has shown promising results in both laboratory settings and animal studies, suggesting that there is potential for the creation of more efficient treatments for this aggressive form of cancer. Moreover, nanotechnological-based miRNA intervention has demonstrated promise in the therapeutic management of neuroblastoma, addressing challenges related to drug delivery and enhancing therapeutic success [9]. Nanomedicines, such as liposomes and doxorubicin-loaded nanocarriers targeted at nucleolin, have also displayed potential in overcoming the limitations of current diagnostic and therapeutic approaches, offering more effective and targeted options [10,11,12]. Additionally, nanoparticle-based drug delivery systems incorporating etoposide have synergized with alpha v integrin antagonists, improving patient care for high-risk neuroblastoma [13]. The co-assembly of amphiphilic antitumor agents has exhibited better antitumor profiles and controlled release behavior, representing a suitable pre-clinical candidate for childhood cancer therapy in neuroblastoma and osteosarcoma [14].
For anaplastic large cell lymphoma (ALCL), protamine nanomedicine with aptamers, dsDNA/drug payload, and siRNA has the potential to offer cell-selective chemotherapy and oncogene-specific gene therapy by targeting diagnostic biomarkers and therapeutic targets [146]. Additionally, nanomedicines and cell-based therapies are currently being investigated in phase I/II clinical trials for neuroblastoma and medulloblastoma, with the aim of reducing drug toxicity and improving efficacy [147]. Nanomedicine has demonstrated promise in overcoming the limitations of conventional chemotherapy for pediatric neuroblastoma [148]. It offers targeted drug delivery, reduces systemic side effects, and improves pharmacokinetic properties, thereby holding the potential to revolutionize the diagnosis and treatment of childhood cancer. The utilization of nanomedicines enables targeted drug delivery and improved pharmacokinetic properties, leading to a reduction in systemic side effects and the potential to revolutionize the diagnosis and treatment of childhood cancer. Further research in this field is of utmost importance to translate these promising advancements into clinical applications and ultimately improve outcomes for pediatric cancer patients. Table 3 summarizes examples of nanocarrier systems utilized in neuroblastoma treatment.
Table 3. Nanosystems in pediatric neuroblastoma treatment.

2.4. Osteosarcoma

Osteosarcoma, a challenging form of cancer, is known for its resistance to chemotherapy and lack of effective targeted therapies. Researchers have made notable advancements in the development of diverse nanocarriers, drug delivery systems, and imaging agents. These innovations aim to improve the effectiveness of treatments while minimizing potential side effects. One particularly promising treatment approach involves alpha-particle therapy utilizing (227)Th and (223)Ra, which has demonstrated efficacy in treating multifocal osteosarcoma while exhibiting limited myelotoxicity and high relative biological effectiveness [15]. Additionally, exosome mimetics derived from BMSCs offer a natural platform for nano drug delivery, delivering potent tumor inhibition activity with reduced side effects [16].
Nanocarriers and targeted drug delivery systems also hold potential in overcoming drug resistance and minimizing side effects [17,18]. For instance, lipid nanoparticles loaded with edelfosine have been found to inhibit cell growth in vitro and prevent metastasis in vivo [19]. Furthermore, self-stabilized hyaluronate nanogels co-delivering doxorubicin and cisplatin have demonstrated enhanced antitumor efficacy and reduced side effects [20].
The use of near-infrared imaging and multifunctional graphene-based nano-drug delivery systems has exhibited highly selective anticancer efficiency by targeting mitochondria, offering synergistic phototherapy for drug-resistant osteosarcoma [21]. Moreover, IL-11Ralpha-targeted nanoparticles have shown superior efficacy in treating osteosarcoma by specifically targeting tumor cells. These nanoparticles have demonstrated strong anti-tumor effects in orthotopic and relapsed osteosarcoma models, as well as patient-derived osteosarcoma xenografts [22].
Figure 3 provides a schematic representation of the fabrication of IL-11Rα-targeting polymersomal Dox and its mechanism of inhibiting the growth, recurrence, and metastasis of malignant osteosarcoma. Additionally, Table 4 summarizes examples of nanocarrier systems employed in osteosarcoma treatment.
Figure 3. Illustration of fabrication of IL-11Rα-targeting polymersomal Dox (IL11-PDox) and strong inhibition of growth, recurrence, and metastasis of malignant osteosarcoma. Adapted with permission from [22].
Table 4. Nanosystems in pediatric osteosarcoma treatment.

2.5. Other Cancers and Cancer-Related Topics

One of the significant challenges in treating pediatric brain tumors, including brain tumors in children, is the blood–brain barrier, which limits effective drug delivery. However, nanotechnology has demonstrated potential with respect to overcoming this obstacle by facilitating drug delivery across the blood–brain barrier [154,155,156,157,158,159,160]. Moreover, nanotechnology offers the ability to selectively target pediatric brain tumors and enhance the bioavailability of phytoconstituents for treating medulloblastoma [158,159]. In the field of ophthalmology, photodynamic therapy utilizing mesoporous silica nanoparticles holds promise for the treatment of retinoblastoma [161]. In regenerative medicine and cancer treatment, nanomedicine-based therapies that combine stem cells with drug delivery systems have shown great potential for achieving improved results [162]. Additionally, gold nanoparticles have been studied for tumor diagnostics through imaging and as delivery devices for targeted therapy in adenoid cystic carcinoma [163]. These examples exemplify the potential of nanotechnology to overcome delivery challenges and provide effective treatments for various pediatric cancers, including osteosarcoma. Table 5 shows additional examples of nanocarrier systems utilized in the treatment of other pediatric cancers or cancer-related disorders.
Table 5. Nanosystems in other pediatric cancer treatments.

3. Infectious Disease Management and Treatment

3.1. Antimalarial/Antibacterial Treatment

In the context of malaria treatment, nanomedicines have proven to be effective tools for targeted drug delivery against the disease [23]. Nanotechnology offers the capability to design strategies that specifically target drug molecules to different stages of the malaria parasite’s life cycle, address drug-resistant strains, and enhance vaccine effectiveness [24].
For the treatment of leishmaniasis, nanotechnology-based drug delivery systems have been developed to minimize toxicity while maintaining therapeutic efficacy [25]. Moreover, nanotechnology presents innovative solutions for administering drugs to pediatric patients affected by malaria, leishmaniasis, toxoplasmosis, and schistosomiasis [171].
Nanoparticles have also been utilized in bioassays for the detection and control of schistosomiasis, offering improved sensitivity, speed, and convenience [26]. In the case of Praziquantel (PZQ), nanocarriers have been developed to overcome the limitations of its low solubility and bioavailability, thereby enhancing its performance [27]. Nanotechnology has also been employed to combat antibiotic resistance by augmenting the antimicrobial efficacy of ceftriaxone against Gram-positive and Gram-negative bacteria using chitosan nanoparticles, providing an alternative to traditional antibiotics [28].
The application of nanotechnology extends to the treatment of pediatric infectious diseases and solid tumors, with its scope ranging from in vitro studies to clinical trials [172]. Additionally, a biosensor employing nano-fabricated structures and anti-E. coli antibodies has exhibited high sensitivity for clinical use in the detection of bacterial infections in human kidneys [29]. Table 6 provides a summary of examples of nanocarrier systems employed in the treatment of pediatric malaria and other bacterial diseases.
Table 6. Nanosystems in pediatric malaria and other bacterial diseases.

3.2. COVID-19

Recent studies have showcased the potential of nanotechnology-based diagnostic methods in accurately detecting extracellular vesicles carrying SARS-CoV-2 RNA in plasma, presenting a promising alternative to traditional respiratory RNA level detection approaches. These advancements, encompassing CRISPR-based and optical-based sensing systems, hold significant promise for the development of efficient and rapid diagnostic techniques for COVID-19 [173,174].
Nanotechnology extends beyond diagnostics, offering promising prospects for treatment modalities, vaccination strategies, and the potential integration of artificial intelligence in the field of infectious diseases, including COVID-19 [175]. Moreover, the potential of electrochemical nano-biosensors, utilizing nanomaterials for signal amplification, has been demonstrated in detecting harmful DNA mutations in newborn infants with high sensitivity, a wide dynamic range, and exceptional specificity. This presents a valuable tool for newborn screening purposes [176]. Table 7 provides an overview of examples of nanocarrier systems employed in the treatment of COVID-19.
Table 7. Nanosystems in pediatric COVID-19 treatment.
Overall, the integration of nanotechnology into the realm of infectious diseases holds potential for the development of innovative and effective diagnostic and treatment strategies. Ongoing research and development efforts in this field are anticipated to yield breakthroughs in the battle against infectious diseases, including malaria, bacterial infections, and viral infections such as SARS-CoV-2. The promising results reported in existing studies indicate that nanotechnology will play a significant role in the future of healthcare, revolutionizing the detection and treatment of various infectious diseases [173,174,175,176].

3.3. TB and HIV

Nanomedicine has paved the way for new treatment possibilities, including the delivery of antimicrobial host defense peptides, which have shown to enhance therapeutic effectiveness and reduce resistance in TB and HIV infections [30]. Nanotechnology-based diagnostic methods have exhibited potential in accurately diagnosing HIV in infants—a challenging population to detect [31]. Furthermore, the formulation of antiretroviral drugs with nanotechnology has improved their bioavailability, reduced dosage requirements, and enhanced treatment outcomes in HIV patients, particularly among pediatric populations [32,33,34].
Regarding TB, nanotechnology-based antigen testing and polymeric micelles have demonstrated high diagnostic accuracy and increased oral bioavailability of rifampicin, respectively, enabling early detection and effective treatment [35,36]. Various nanotechnology-based strategies have been proposed to develop more effective and patient-compliant medicines for TB treatment, including targeting infection reservoirs and overcoming drug resistance [37]. A child-friendly nanoemulsion containing rifampicin has shown promise in increasing drug bioavailability and reducing treatment failure in pediatric TB patients [39]. With increased institutional support, the integration of nanomedicine and genomic research holds the potential to achieve TB elimination by 2050 [38]. Table 8 provides a summary of examples of nanocarrier systems used in the treatment of pediatric TB and HIV.
Table 8. Nanosystems in pediatric TB and HIV treatments.

3.4. Respiratory and Pulmonary Diseases

Nanoparticles have proven effective in preventing biofilm formation and colonization on endotracheal tubes in pediatric patients with VAP, thereby reducing the risk of infection [40]. Moreover, nanomodified endotracheal tubes have shown substantial reductions in the growth of P. aeruginosa, effectively combating VAP [41]. Nanotechnology-based therapeutic approaches hold promise for the detection and treatment of RSV with maximum efficacy and minimal side effects [42]. Gold nanorods, for instance, have demonstrated the potential to inhibit RSV by activating the immune response, making them a potential antiviral agent against RSV [43]. In cystic fibrosis, nanotechnology has facilitated the development of the Nanoduct sweat test system, which offers improved ease of use and higher diagnostic success rates in newborns compared to the Macroduct/Gibson and Cooke methods [44]. Furthermore, nanotechnology-based approaches have shown promise in managing the pain associated with cystic fibrosis, a common affliction for CF patients [45]. Table 9 provides an overview of nanocarrier systems utilized in the treatment of pediatric respiratory and pulmonary diseases.
Table 9. Nanosystems in pediatric respiratory and pulmonary diseases.

3.5. Environmental Health and Infectious Diseases

In recent years, the application of nanotechnology in the field of environmental health and infectious diseases has garnered significant attention from scientists and researchers [46]. This emerging field has demonstrated remarkable potential in the detection and treatment of various diseases. However, it is important to acknowledge the associated risks. Studies using human placental perfusion models have indicated that nanoparticles have the ability to cross the placental barrier, raising concerns about potential risks to developing fetuses [46]. Nevertheless, nanotechnology has shown effectiveness in detecting water-borne parasites and mitigating biological contamination in drinking water, especially in areas with inadequate sanitation facilities in developing countries [47,48]. Nanotechnology-based assays and nanodevices have also exhibited promise in the identification of water-borne pathogens, which is crucial for safeguarding public health [49]. Given the escalating production of environmental pollutants and the health threats posed by climate change, concerted efforts are necessary to tackle these environmental health challenges [178]. Moreover, nanotechnology offers potential solutions for combatting the lethal effects of scorpion envenomation and presents strategies for the treatment and control of viral infections [50,51]. While PCR-based assays currently remain the gold standard for the detection of certain viruses, researchers are actively exploring the advantages of nanotechnology and advanced genetic platforms for therapeutic interventions [52]. Table 10 provides an overview of nanocarrier systems employed in the treatment of pediatric infectious diseases related to the environment.
Table 10. Environmental health and pediatric infectious diseases.

5. Other Pediatric Applications

Highly sensitive assays using LC-MS/MS technology have identified melatonin and N-acetylserotonin as potential biomarkers for sleep-related disorders, providing valuable insights for diagnosis and treatment [188]. In audiology, nanotechnology research has shown promise in developing advanced sound and hearing implants, offering a potential breakthrough for individuals with profound deafness [189]. Moreover, the presence of metallic particles in human tonsil tissue and amniotic fluid has raised intriguing possibilities regarding their role in disease causation and emerging nanopathology [190].
The concern over nanoparticle exposure has led to investigations into resuspension rates, revealing variations depending on the product, flooring, and resuspension force. Products containing copper, silver, and zinc nanomaterials exhibited higher rates, highlighting the importance of further research and regulation in this area [191]. Advancements in drug delivery systems and nanomedicines hold promise for treating degenerative ocular diseases that manifest in childhood, offering the potential to significantly enhance the quality of life for affected pediatric patients [192]. Similarly, the use of nanocarrier-mediated drug delivery has garnered support and is clinically recommended for the treatment of atopic dermatitis [185].
Studies exploring microbial interactions have unveiled the strong binding of Streptococcus mutans-derived exoenzyme GtfB to Candida albicans, shedding light on the modulatory role of this interaction [193]. Additionally, the implementation of a nano-selenium reactive barrier approach has shown success in suppressing mercury release from compact fluorescent lamps, aiding in the identification of mercury contamination sources and achieving significant reductions in exposure scenarios [194]. A gold nanoparticle-based dynamic light scattering (DLS) probe has demonstrated potential for on-site monitoring of lead (Pb) levels in various samples, detecting concentrations as low as 100 ppt, which surpasses the EPA standard limit by nearly two orders of magnitude [195]. Table 16 provides an overview of nanocarrier systems employed in other areas of pediatric health.
Table 16. Nanosystems in other pediatric disorders.

6. Potential Risks and Health Effects

Despite its potentially transformational role, it is crucial to carefully assess and address the potential risks associated with this rapidly advancing technology. Several studies have shed light on the potential health implications of nanotechnology, emphasizing the need for caution. For instance, one study [103] investigated the impact of engineered nanoparticles on children’s health, while others [104,105] focused on the neurotoxicity of nanoparticles. Additionally, the health effects of carbon nanoparticles and ultrafine particles warrant further investigation [106,107,108].
Although graphene is generally considered a safer alternative to carbon nanotubes, it is still essential to implement specific safety protocols when working with any type of nanomaterial. Studies have shown that nanoparticles can impose metabolic burden, oxidative stress, and potentially alter milk composition in breastfeeding systems, indicating potential risks [196]. Moreover, children are particularly vulnerable to the potential hazards associated with engineered nanoparticles, necessitating focused research on exposure levels and health consequences [197].
There is a significant lack of public understanding about nanotechnology, especially among middle-school children, despite its profound impact on various industries and society as a whole [198]. Therefore, it is crucial to educate the public about both the potential risks and benefits of nanotechnology. While research is needed to comprehend the disparities between children and adults in terms of harmful effects induced by exposure to ultrafine particulate matter, the unique physicochemical properties of nanoparticles offer promising opportunities for biomedical applications. Hence, it is essential to explore the potential benefits of nanoparticles within the field of nanotechnology [108]. Table 17 provides an overview of potential health risks associated with nanosystems in pediatric nanomedicine.
Table 17. Nanosystems and their potential risks and impact on pediatric health.
In conclusion, while nanotechnology holds tremendous promise, it is imperative to carefully evaluate and mitigate its potential risks to ensure its safe and responsible utilization.

7. Conclusions

In conclusion, nanotechnology has been identified as a potential tool in the field of pediatric medicine, offering new possibilities for the diagnosis and treatment of various conditions. Its use in pediatric oncology shows promise, as it allows for targeted drug delivery, reduced toxicity, and combined immunotherapy, which may have benefits in treating specific pediatric tumors. Nanotechnology-based approaches have shown potential in delivering drugs directly to the affected areas in pediatric cancers such as leukemia and neuroblastoma. Additionally, nanotechnology has potential applications beyond cancer treatment, including the management of pediatric infectious diseases, respiratory and pulmonary conditions, and environmental health concerns. The integration of nanotechnology has led to advancements in drug delivery, diagnostics, and treatment outcomes. However, it is important to approach nanotechnology carefully and ensure the responsible use of nanoparticles. Thorough research is needed to understand their safety profiles, particularly in relation to potential health risks in children.

Author Contributions

Conceptualization, H.O.; writing—original draft preparation, H.O. and K.M.; writing—review and editing, H.O. and K.M. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Conflicts of Interest

The authors partly used OpenAI’s large-scale language-generation model. The authors reviewed, revised, and edited the document for accuracy and take full responsibility for the content of this publication. The authors declare no conflict of interest.

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