Search Results (71)

Traditional pharmacotherapy is often constrained by suboptimal bioavailability and systemic toxicity. Biomolecularly inspired nano-drug delivery systems (nano-DDS) have emerged as precise platforms to overcome these barriers by orchestrating molecular interactions at the bio-nano interface. This review systematically evaluates the molecular recognition mechanisms and biochemical principles governing nano-DDS performance. We systematically evaluate how passive targeting relies on the EPR effect—dictated by the nanocarrier’s physicochemical properties—and how active targeting exploits ligand-receptor affinity to enhance cellular uptake. Special emphasis is placed on bioresponsive strategies that utilize pathological cues—such as pH gradients, redox potential, and enzymatic activity—for intelligent, on-demand drug release. Furthermore, we discuss structure-function relationships in lipid, polymeric, and biologically derived systems, highlighting their roles in modulating therapeutic signaling in oncology and inflammatory diseases. Finally, translational hurdles and emerging AI-driven molecular design strategies are critically examined. Full article

Glioblastoma (GB) remains the most aggressive primary brain malignancy, with the Stupp regimen persisting as the standard of care for nearly two decades despite poor survival outcomes. This review was synthesized by extensively reviewing and analyzing the literature from PubMed, Scopus, and Web of Science to evaluate the emerging promising therapeutic and diagnostic strategies for combating GB. Results indicate significant progress in molecularly targeted therapies, biomimetic nanocarriers, and advanced radiotherapy. While immunotherapeutic approaches, such as checkpoint inhibitors and vaccines, show variable clinical success, the integration of bioinformatics and machine learning has significantly enhanced treatment response prediction. Furthermore, advances in radiomics and molecular imaging have improved the differentiation between true tumor progression and pseudoprogression, potentially reducing invasive diagnostic requirements. Additionally, other emerging and investigational adjuvant therapeutic approaches have shown promise. We conclude that, while multimodal strategies integrating molecular and computational approaches offer a path toward personalized GB management, significant barriers—namely tumor heterogeneity and the blood–brain barrier—persist. Future research must prioritize precision-based combinatorial models to successfully translate these preclinical advancements into improved clinical outcomes for patients. Full article

Although nanomedicine has enabled significant advances in drug delivery, the clinical translation of conventional synthetic nanocarriers is limited by immune clearance, non-specific biodistribution, and gastrointestinal instability. This poses major challenges for therapy targeting the intestines. Cell membrane-coated nanotechnology (CMCT) and membrane vesicle-based systems have emerged as biomimetic platforms integrating synthetic nanomaterials with naturally derived biological interfaces. These biohybrid systems inherit biological functions originating from cells, including immune evasion, prolonged circulation, lesion homing, and microenvironment-responsive interactions, through the direct transfer of intact membrane components. This review summarizes recent advances in CMCT and membrane vesicle-based strategies for intestinal drug delivery. It covers fabrication methodologies, programmable manufacturing approaches, and functional regulation enabled by diverse membrane sources and hybrid engineering designs. Applications in inflammatory bowel disease, colorectal cancer, and intestinal infections are highlighted, emphasizing key therapeutic mechanisms, such as targeting inflammation, neutralizing toxins, modulating the immune system, and regulating the microbiome. We also discuss the major challenges of translation, such as preserving membrane and coating integrity, ensuring oral stability, achieving batch reproducibility, and ensuring biosafety. Overall, this review establishes a conceptual and engineering framework to guide the transition of membrane-based nanocarriers from passive biomimicry to adaptive, clinically translatable intestinal delivery systems. Full article

Background/Objectives: Myocardial ischemia–reperfusion injury (MIRI) remains an ever-growing threat in the field of cardiology, as it has become a major risk factor for unfavorable outcomes following reperfusion therapies. Oxidative stress and inflammation remain the key pathophysiological mechanisms underlying MIRI, and the presently available treatments fail to prevent this process effectively. This systematic review aimed to summarize and critically assess the latest preclinical research (2020–2026) on nanocarrier-based interventions targeting oxidative stress in MIRI, highlighting the potential of the new nanostructures in cardioprotection. Methods: A total of 24 studies meeting the PRISMA criteria have been found through a literature search of PubMed, Embase, and Web of Science databases published between 2020 and 2026. The studies eligible for inclusion had focused on the efficacy of nanocarrier-based interventions in preclinical studies of MIRI. Results: Of the 24 included studies, all investigated nanocarrier-based interventions in preclinical models of MIRI. In vitro, ex vivo, and in vivo models were diverse, with most studies being a combination of both in vitro and in vivo models. Commonly studied were lipid-based nanocarriers, polymeric nanoparticles, and biomimetic nanocarriers. Across studies assessed for this review, treatments with nanocarriers were seen to suppress inflammatory and oxidative stress pathways, with a few studies showing a suppression of cardiomyocyte apoptosis. Cardiac function was restored as determined by echocardiography analyses or ex vivo models of the myocardium, thus validating that the nanocarrier-mediated therapies are effective against MIRI. Conclusions: The analyzed preclinical studies indicate that the described therapies could provide a promising basis for future clinical trials in the treatment of MIRI, provided their safety and efficacy are confirmed in clinical trials. Full article

Nanomaterials are emerging versatile platforms for therapeutic delivery, as they offer precise control over drug, antioxidant, and genetic payload transport across biological barriers. Inorganic, organic, hybrid, and biomimetic systems are the major classes of nanomaterials, which all have different physicochemical properties such as size, surface charge, and surface functionalization. These properties collectively influence stability, biodistribution, cellular uptake, and release kinetics. Engineering strategies are increasingly using stimuli-responsive designs that are triggered by pH, reactive oxygen species (ROS), and intracellular redox gradients to perform spatially and temporally controlled delivery. Antioxidant and redox-modulating nanocarriers are of great importance as they overcome the limited bioavailability and nonspecific activity of conventional antioxidants by improving stability, targeting oxidative microenvironments, and allowing for regulated release. Improvements in lipid, polymeric, and inorganic nanoplatforms have also developed gene delivery applications, including siRNA, mRNA, and CRISPR/Cas systems, to provide better cytosolic release and precise therapeutics. When diagnostic imaging is integrated with therapy through theranostic nanoparticles, real-time monitoring and personalized intervention are possible. Safety, scalable manufacturing, and regulatory alignment are some challenges that show the need for standardization and translational procedures to utilize the potential of theranostic nanomedicine. Full article

As cancer mortality rates rise globally, malignancies have become the second leading cause of death. Recently, efforts have been made to understand the impact of the tumor microenvironment that involves fluid shear forces. Biomechanical stimulation, which uses shear stress to activate mechanosensitive ion channels, e.g., Piezo1, increases calcium influx into the intracellular space and activates T cells. Novel 3D cancer cultures with T cells have been proposed. Such models use cell/scaffold constructs to recapitulate interactions between cells and the extracellular matrix. In addition, flow perfusion bioreactors investigate the impact of fluid shear forces on immune and/or cancer cells. These bioreactors have biosensors that allow monitoring of immune cell activation. Furthermore, they provide a biomimetic environment for the study of the interaction of T cells and cancer cells. Hence, immune checkpoint inhibitors have demonstrated immunotherapeutic efficacy, but a single-target blockade has often proved insufficient. Co-delivery of CCL19 pDNA and the PD-1/PD-L1 interaction inhibitor BMS-1 using RGD-modified nanocarriers targeting tumor integrins enhanced local antitumor immunity. This review highlights recent insights into how fluid shear stress (FSS) regulates cancer progression and immune responses in three-dimensional in vitro models, with a focus on bioreactors and the surface modification of scaffold materials. Full article

Background/Objectives: Despite the clinical success of immune checkpoint blockade (ICB), its efficacy remains limited in immunologically “cold” tumors, primarily due to poor immunogenicity and an immunosuppressive tumor microenvironment (TME). Chemo-immunotherapy offers a potential strategy to enhance ICB response, yet its application is often hindered by inadequate tumor-targeted delivery and systemic immunosuppressive side effects. Biomimetic nanotechnology represents a promising approach to overcoming these limitations by improving drug delivery and facilitating effective combination regimens. Methods: We developed a biomimetic nanosystem (NVs@DOX) through genetic engineering of cellular membranes and optimized nanoformulation techniques, enabling co-delivery of doxorubicin (DOX) and ICB agents. This design aims to maximize synergistic antitumor effects while minimizing adverse impacts. Results: In vitro studies demonstrated the potent cytotoxicity of NVs@DOX, including significant inhibition of cancer cell proliferation and complete suppression of colony formation. In a 4T1 murine breast cancer model, NVs@DOX treatment led to substantial tumor growth inhibition (approximately 72%) without notable body weight loss, underscoring a favorable safety profile alongside enhanced therapeutic efficacy. Conclusions: The NVs@DOX platform effectively integrates doxorubicin with ICB within a biomimetic nanocarrier, significantly improving chemo-immunotherapy outcomes. This strategy highlights the potential of genetically engineered cellular nanoparticles as a promising combinatorial approach for the treatment of breast cancer. Full article

Cell membrane-coated nanoparticles represent a biomimetic drug delivery approach that integrates biological membrane functions with synthetic nanomaterials. Among the various membrane sources, those derived from blood cells such as red blood cells, platelets, and leukocytes offer distinctive advantages, including immune evasion, prolonged systemic circulation, and selective tissue targeting. These properties collectively enable efficient and biocompatible delivery of therapeutic agents to diseased tissues, minimizing off-target effects and systemic toxicity. This review focuses on blood cell membrane-derived nanocarriers as drug delivery and immune-regenerative platforms, in which membrane-mediated immunomodulation synergizes with therapeutic payloads to address inflammatory or degenerative pathology. We discuss recent advances in blood cell membrane coating technologies, including membrane isolation, nanoparticle core selection, fabrication techniques, and the development of hybrid and engineered membrane systems that enhance therapeutic efficacy through integrated immune regulation and localized drug action. To illustrate these advances, we also compile membrane type-specific nanocarrier systems, summarizing their core nanoparticle designs, coating strategies, therapeutic cargoes, and associated disease models. Challenges related to biological source variability, scalability, safety, and regulatory standardization remain important considerations for clinical translation. In this review we systematically address these issues and discuss emerging solutions and design strategies aimed at advancing blood cell membrane-based nanocarriers toward clinically viable immune-regenerative therapies. Full article

Antimicrobial peptides have been increasingly recognized as potential anticancer agents, with the KLA peptide (KLAKLAK₂) being one of the most well-known and successful examples. The research interest in the KLA peptide is attributed to its ability to induce apoptosis in cancer cells by disrupting the mitochondrial membrane. However, the KLA peptide exhibits poor cellular uptake and it lacks targeting specificity, limiting its clinical potential in cancer therapy. In this review, recent advances in nano-engineered delivery platforms for overcoming the limitations of KLA peptides and enhancing their anticancer efficacy are discussed. Specifically, various nanocarrier systems that enable targeted delivery, controlled release and/or improved bioavailability, including pH-responsive nanosystems, photo-chemo combination liposomes, self-assembled peptide-based nanostructures, nanogel-based delivery systems, homing domain-conjugated KLA structures, inorganic-based nanoparticles, and biomimetic nanocarriers, are highlighted. Additionally, synergistic strategies for combining KLA with chemotherapeutic agents or immunotherapeutic agents to overcome resistance mechanisms in cancer cells are examined. Finally, key challenges for the clinical application of these nanotechnologies are summarized and future directions are proposed. Full article

The development of safer, more effective, and tumor-specific therapeutic strategies remains a major challenge in oncology. Conventional treatments such as chemotherapy and radiotherapy often cause severe side effects and are limited in their ability to target deep-seated or resistant tumors. In this context, sonodynamic therapy (SDT) has emerged as a promising, non-invasive option, harnessing low-intensity ultrasound to activate sonosensitizers deep within tissues and generate cytotoxic reactive oxygen species (ROS) that selectively induce cancer cell death. Interestingly, SDT can also be combined with other therapies to achieve synergistic effects. However, despite encouraging preclinical results, SDT clinical translation is hindered by the poor aqueous solubility, instability, and low tumor specificity of traditional sonosensitizers. To overcome these limitations, recent studies have focused on employing extracellular vesicles (EVs), especially exosomes, as natural, biomimetic nanocarriers for sonosensitizer delivery. EVs offer unique advantages, including high biocompatibility, low immunogenicity, and intrinsic tumor-targeting ability, which make them ideal platforms for improving the therapeutic precision of SDT. Although several delivery strategies have been proposed, a comprehensive and focused overview of approaches specifically designed to enhance SDT performance using EVs is currently lacking. This review summarizes recent advances in integrating EVs with SDT for cancer treatment. It discusses the mechanisms underlying SDT, the engineering strategies developed to enhance exosome functionality, and the synergistic effects achieved through this combination. Furthermore, this review emphasizes that EV-based SDT not only enhances tumor accumulation of the therapeutic nanoplatforms, but also actively remodels the tumor microenvironment by improving oxygen availability, reversing immunosuppressive conditions, and triggering durable antitumor responses. Finally, the review addresses the translational challenges and outlines the critical future directions required to advance this promising therapeutic approach toward clinical application. Full article

Ovarian cancer continues to be the most lethal gynaecological malignancy, principally due to its late-stage diagnosis, extensive peritoneal dissemination, chemoresistance, and limitations of current imaging and therapeutic strategies. By optimising pharmacokinetics, refining tumour-selective drug delivery, and supporting high-resolution, multimodal imaging, nanomedicine offers a versatile platform to address these limitations. In this review, current progress across lipid-based, polymeric, inorganic, hybrid, and biomimetic nanocarriers is synthesised, emphasising how tailored physiochemical properties, surface functionalisation, and stimuli-responsive designs can improve tumour localisation, surmount stromal and ascetic barriers, and enable controlled drug release. Concurrently, significant advancement in imaging nanoprobes, including magnetic resonance imaging (MRI), positron emission tomography (PET)/single-photon emission computed tomography (SPECT), optical, near-infrared imaging (NIR), ultrasound, and photoacoustic systems, has evolved early lesion detection, intraoperative guidance, and quantitative monitoring of treatment. Diagnosis and therapy are further integrated within single platforms by emerging theranostic constructs, encouraging real-time visualisation of drug distribution and treatment response. Additionally, immune-nanomedicine, intraperitoneal depot systems, and nucleic acid-centred nanotherapies offer promising strategies to address immune suppression and molecular resistance in advanced ovarian cancer. In spite of noteworthy achievements, clinical translation is limited by complex manufacturing requirements, challenges with safety and stability, and restricted patient stratification. To unlock the full clinical potential of nanotechnology in ovarian cancer management, constant innovation in scalable design, regulatory standardisation, and integration of precision biomarkers will be necessary. Full article

Over the years, cancer has continued to be a leading global health threat, prompting researchers to explore advanced therapies that go beyond traditional treatments like chemotherapy and radiotherapy. Among these advanced therapies, gene therapy and immunotherapy have shown significant promise in treating cancer by either altering genetic makeup or stimulating the immune system. However, their clinical applications face significant obstacles such as poor drug delivery, rapid degradation, and immune system clearance. Hybrid nanocarriers have emerged as a transformative development in modern precision oncology, enabling the co-delivery of gene therapy and immunotherapy agents in a highly targeted manner to address the persistent limitations of traditional cancer treatments. This review focuses on hybrid nanocarrier systems specifically engineered for co-delivery applications and critically evaluates when and how these multifunctional platforms outperform conventional single-modality or non-hybrid formulations. We compare key hybrid architectures in terms of payload compatibility, pharmacokinetics, immune modulation, and translational readiness, and examine the influence of tumor microenvironmental characteristics on their therapeutic performance. Particular emphasis is placed on stimuli-responsive designs, biomimetic surface engineering, and artificial intelligence–assisted optimization as emerging strategies to enhance co-delivery efficacy. By synthesizing current evidence and identifying key scientific and manufacturing gaps, this review aims to provide a practical foundation for advancing hybrid nanocarriers from laboratory development to clinically meaningful, personalized cancer therapies. Full article

Magnetic microrobots have emerged as a promising platform for drug delivery in recent years. By enabling remotely controlled motion and precise navigation under external magnetic fields, these systems offer new solutions to overcome the limitations of traditional drug delivery nanocarriers, such as inadequate tissue penetration and heterogeneous biodistribution. Over the past few years, significant advancements have been made in the structural design of magnetic microrobots, as well as in drug loading techniques and stimuli-responsive drug release mechanisms, thereby demonstrating distinct advantages in enhancing therapeutic efficacy and targeting precision. This review provides a comprehensive overview of magnetic drug delivery microrobots, which are categorised into biomimetic structural, bio-templated and advanced material-based types, and introduces their differences in propulsion efficiency and biocompatibility. Additionally, drug loading and release strategies are summarised, including physical adsorption, covalent coupling, encapsulation, and multistimuli-responsive mechanisms such as pH, enzyme activity and thermal triggers. Overall, these advancements highlight the significant potential of magnetic microrobots in targeted drug delivery and emphasise the key challenges in their clinical translation, such as biological safety, large-scale production and precise targeted navigation within complex biological environments. Full article

Background/Objectives: Advanced drug delivery systems (DDSs) are essential for targeted delivery, controlled release, and reduced systemic toxicity, but their clinical adoption is limited by biological barriers, manufacturing complexities, and cost. The aim of this systematic review is to critically evaluate the quantitative relationships between platform design, overcoming biological barriers, and clinical translation outcomes for DDS developed between 2016 and 2025. Methods: A comprehensive literature search was conducted in PubMed/MEDLINE, Scopus, and Web of Science (January 2016–April 2025) in accordance with the PRISMA 2020 guidelines. Included studies focused on experimental or clinical data for nanocarrier platforms (liposomes, lipid nanoparticles, polymer systems, biomimetic carriers, extracellular vesicles). Data on platform characteristics, interactions with barriers, pharmacokinetics, manufacturing, and clinical outcomes were extracted and synthesized in narrative form due to the significant methodological heterogeneity. Results: An analysis of 77 included studies confirms that successful clinical translation depends on matching the physicochemical properties of the carrier (size, surface chemistry, material) to specific biological barriers. Liposomes and lipid nanoparticles (LNPs) remain the most clinically validated platforms, exploiting the EPR effect and liver tropism, respectively. Key engineering solutions include stealth coatings, ligand-mediated targeting, and stimulus-responsive materials to overcome barriers such as mononuclear phagocyte system clearance, the blood–brain barrier, and mucosal barriers. Microfluidic and continuous manufacturing processes enable reproducibility, but scalability, cost, and immunogenicity (e.g., anti-PEG responses) remain key translational challenges. Engineered extracellular vesicles, biomimetic carriers, and 3D/4D-printed systems combined with AI-driven design demonstrate the potential for personalized, adaptive delivery. Conclusions: Cutting-edge DDSs have validated their clinical value, but realizing their full potential requires a holistic, patient-centered design approach integrating barrier-specific engineering, scalable manufacturing, and rigorous safety assessment from the earliest stages of development. Further progress will depend on standardizing methods for new platforms (e.g., extracellular vesicles), implementing digital and AI tools, and ensuring translational feasibility as a fundamental principle. Full article

Cancer continues to pose a major global health burden, with conventional therapeutic modalities such as surgical resection, chemotherapy, radiotherapy, and immunotherapy often hindered by limited tumor specificity, substantial systemic toxicity, and the emergence of multidrug resistance. The rapid advancement of nanotechnology has introduced functionalized nanomaterials as innovative tools in the realm of precision oncology. These nanoplatforms possess desirable physicochemical properties, including tunable particle size, favorable biocompatibility, and programmable surface chemistry, which collectively enable enhanced tumor targeting and reduced off-target effects. This review systematically examines recent developments in the application of nanomaterials for cancer therapy, with a focus on several representative nanocarrier systems. These include lipid-based formulations, synthetic polymeric nanoparticles, inorganic nanostructures composed of metallic or non-metallic elements, and carbon-based nanomaterials. In addition, the article outlines key strategies for functionalization, such as ligand-mediated targeting, stimulus-responsive drug release mechanisms, and biomimetic surface engineering to improve in vivo stability and immune evasion. These multifunctional nanocarriers have demonstrated significant potential across a range of therapeutic applications, including targeted drug delivery, photothermal therapy, photodynamic therapy, and cancer immunotherapy. When integrated into combinatorial treatment regimens, they have exhibited synergistic therapeutic effects, contributing to improved efficacy by overcoming tumor heterogeneity and resistance mechanisms. A growing body of preclinical evidence supports their ability to suppress tumor progression, minimize systemic toxicity, and enhance antitumor immune responses. This review further explores the design principles of multifunctional nanoplatforms and their comprehensive application in combination therapies, highlighting their preclinical efficacy. In addition, it critically examines major challenges impeding the clinical translation of nanomedicine. By identifying these obstacles, the review provides a valuable roadmap to guide future research and development. Overall, this work serves as an important reference for researchers, clinicians, and regulatory bodies aiming to advance the safe, effective, and personalized application of nanotechnology in cancer treatment. Full article