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16 pages, 3287 KiB

Open AccessArticle

Unveiling the Native Morphology of Extracellular Vesicles from Human Cerebrospinal Fluid by Atomic Force and Cryogenic Electron Microscopy

by Mario Kurtjak, Sami Kereïche, Damir Klepac, Hrvoje Križan, Marko Perčić, Vedrana Krušić Alić, Teja Lavrin, Metka Lenassi, Karmen Wechtersbach, Nika Kojc, Marija Vukomanović, Siniša Zrna, Maša Biberić, Robert Domitrović, Kristina Grabušić and Mladenka Malenica

Biomedicines 2022, 10(6), 1251; https://doi.org/10.3390/biomedicines10061251 - 27 May 2022

Cited by 7 | Viewed by 2349

Abstract

Extracellular vesicles (EVs) are membranous structures in biofluids with enormous diagnostic/prognostic potential for application in liquid biopsies. Any such downstream application requires a detailed characterization of EV concentration, size and morphology. This study aimed to observe the native morphology of EVs in human [...] Read more.

Extracellular vesicles (EVs) are membranous structures in biofluids with enormous diagnostic/prognostic potential for application in liquid biopsies. Any such downstream application requires a detailed characterization of EV concentration, size and morphology. This study aimed to observe the native morphology of EVs in human cerebrospinal fluid after traumatic brain injury. Therefore, they were separated by gravity-driven size-exclusion chromatography (SEC) and investigated by atomic force microscopy (AFM) in liquid and cryogenic transmission electron microscopy (cryo-TEM). The enrichment of EVs in early SEC fractions was confirmed by immunoblot for transmembrane proteins CD9 and CD81. These fractions were then pooled, and the concentration and particle size distribution were determined by Tunable Resistive Pulse Sensing (around 10¹⁰ particles/mL, mode 100 nm) and Nanoparticle Tracking Analysis (around 10⁹ particles/mL, mode 150 nm). Liquid AFM and cryo-TEM investigations showed mode sizes of about 60 and 90 nm, respectively, and various morphology features. AFM revealed round, concave, multilobed EV structures; and cryo-TEM identified single, double and multi-membrane EVs. By combining AFM for the surface morphology investigation and cryo-TEM for internal structure differentiation, EV morphological subpopulations in cerebrospinal fluid could be identified. These subpopulations should be further investigated because they could have different biological functions. Full article

(This article belongs to the Special Issue Advances in Nanomedicine for Disease Treatment and Diagnosis)

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20 pages, 8062 KiB

Open AccessArticle

Clinical Feasibility Study of Gold Nanoparticles as Theragnostic Agents for Precision Radiotherapy

by José Antonio López-Valverde, Elisa Jiménez-Ortega and Antonio Leal

Biomedicines 2022, 10(5), 1214; https://doi.org/10.3390/biomedicines10051214 - 23 May 2022

Cited by 5 | Viewed by 2267

Abstract

Background: Gold nanoparticles (AuNP) may be useful in precision radiotherapy and disease monitoring as theragnostic agents. In diagnostics, they can be detected by computerized tomography (CT) because of their higher atomic number. AuNP may also improve the treatment results in radiotherapy due to [...] Read more.

Background: Gold nanoparticles (AuNP) may be useful in precision radiotherapy and disease monitoring as theragnostic agents. In diagnostics, they can be detected by computerized tomography (CT) because of their higher atomic number. AuNP may also improve the treatment results in radiotherapy due to a higher cross-section, locally improving the physically absorbed dose. Methods: Key parameters values involved in the use of AuNP were imposed to be optimal in the clinical scenario. Mass concentration of AuNP as an efficient contrast agent in clinical CT was found and implemented in a Monte Carlo simulation method for dose calculation under different proposed therapeutic beams. The radiosensitization effect was determined in irradiated cells with AuNP. Results: an AuNP concentration was found for a proper contrast level and enhanced therapeutic effect under a beam typically used for image-guided therapy and monitoring. This lower energetic proposed beam showed potential use for treatment monitoring in addition to absorbed dose enhancement and higher radiosensitization at the cellular level. Conclusion: the results obtained show the use of AuNP concentration around 20 mg Au·mL⁻¹ as an efficient tool for diagnosis, treatment planning, and monitoring treatment. Simultaneously, the delivered prescription dose provides a higher radiobiological effect on the cancer cell for achieving precision radiotherapy. Full article

(This article belongs to the Special Issue Advances in Nanomedicine for Disease Treatment and Diagnosis)

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12 pages, 2633 KiB

Open AccessArticle

Administration Routes as Modulators of the Intrahepatic Distribution and Anti-Anemic Activity of Salicylic Acid/Fe3O4 Nanoparticles

by Bogdan Mîndrilă, Sandra-Alice Buteică, Ion Mîndrilă, Dan-Eduard Mihaiescu, Marina-Daniela Mănescu and Ion Rogoveanu

Biomedicines 2022, 10(5), 1213; https://doi.org/10.3390/biomedicines10051213 - 23 May 2022

Cited by 1 | Viewed by 1724

Abstract

The liver is a key organ in the pharmacokinetics of iron oxide nanoparticles (IONPs). This paper examined how the intravenous (IV) or intragastric (IG) route of administration influenced the intrahepatic distribution or therapeutic effects of IONPs. Wistar rats, some with bleeding-induced anemia, and [...] Read more.

The liver is a key organ in the pharmacokinetics of iron oxide nanoparticles (IONPs). This paper examined how the intravenous (IV) or intragastric (IG) route of administration influenced the intrahepatic distribution or therapeutic effects of IONPs. Wistar rats, some with bleeding-induced anemia, and iron oxide nanoparticles functionalized with salicylic acid (SaIONPs), with an average hydrodynamic diameter of 73 nm, compatible with rat sinusoid fenestrations, were used in this study. Light microscopy and multispectral camera analysis of Prussian blue labeled SaIONPs allowed mapping of intrahepatic nanoparticle deposits and revealed intrahepatic distribution patterns specific to each route of administration: loading of Kupffer cells and periportal hepatocytes when the IV route was used and predominant loading of hepatocytes when the IG route was used. Reducing the time to return to baseline values for hemoglobin (HGB) in rats with bleeding-induced anemia with IV or IG therapy has proven the therapeutic potential of SaIONPs in such anemias. The long-term follow-up showed that IV therapy resulted in higher HGB values. Proper use of the administration routes may modulate intrahepatic distribution and therapeutic effects of nanoparticles. These results may be beneficial in theragnosis of liver disease. Full article

(This article belongs to the Special Issue Advances in Nanomedicine for Disease Treatment and Diagnosis)

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Review

Jump to: Research

18 pages, 1325 KiB

Open AccessReview

Detection of Biological Molecules Using Nanopore Sensing Techniques

by Iuliana Șoldănescu, Andrei Lobiuc, Mihai Covașă and Mihai Dimian

Biomedicines 2023, 11(6), 1625; https://doi.org/10.3390/biomedicines11061625 - 02 Jun 2023

Cited by 3 | Viewed by 2473

Abstract

Modern biomedical sensing techniques have significantly increased in precision and accuracy due to new technologies that enable speed and that can be tailored to be highly specific for markers of a particular disease. Diagnosing early-stage conditions is paramount to treating serious diseases. Usually, [...] Read more.

Modern biomedical sensing techniques have significantly increased in precision and accuracy due to new technologies that enable speed and that can be tailored to be highly specific for markers of a particular disease. Diagnosing early-stage conditions is paramount to treating serious diseases. Usually, in the early stages of the disease, the number of specific biomarkers is very low and sometimes difficult to detect using classical diagnostic methods. Among detection methods, biosensors are currently attracting significant interest in medicine, for advantages such as easy operation, speed, and portability, with additional benefits of low costs and repeated reliable results. Single-molecule sensors such as nanopores that can detect biomolecules at low concentrations have the potential to become clinically relevant. As such, several applications have been introduced in this field for the detection of blood markers, nucleic acids, or proteins. The use of nanopores has yet to reach maturity for standardization as diagnostic techniques, however, they promise enormous potential, as progress is made into stabilizing nanopore structures, enhancing chemistries, and improving data collection and bioinformatic analysis. This review offers a new perspective on current biomolecule sensing techniques, based on various types of nanopores, challenges, and approaches toward implementation in clinical settings. Full article

(This article belongs to the Special Issue Advances in Nanomedicine for Disease Treatment and Diagnosis)

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25 pages, 1731 KiB

Open AccessEditor’s ChoiceReview

Lipid Nanoparticles as Delivery Vehicles for Inhaled Therapeutics

by Ellenmae W. X. Leong and Ruowen Ge

Biomedicines 2022, 10(9), 2179; https://doi.org/10.3390/biomedicines10092179 - 02 Sep 2022

Cited by 35 | Viewed by 6469

Abstract

Lipid nanoparticles (LNPs) have emerged as a powerful non-viral carrier for drug delivery. With the prevalence of respiratory diseases, particularly highlighted by the current COVID-19 pandemic, investigations into applying LNPs to deliver inhaled therapeutics directly to the lungs are underway. The progress in [...] Read more.

Lipid nanoparticles (LNPs) have emerged as a powerful non-viral carrier for drug delivery. With the prevalence of respiratory diseases, particularly highlighted by the current COVID-19 pandemic, investigations into applying LNPs to deliver inhaled therapeutics directly to the lungs are underway. The progress in LNP development as well as the recent pre-clinical studies in three main classes of inhaled encapsulated drugs: small molecules, nucleic acids and proteins/peptides will be discussed. The advantages of the pulmonary drug delivery system such as reducing systemic toxicity and enabling higher local drug concentration in the lungs are evaluated together with the challenges and design considerations for improved formulations. This review provides a perspective on the future prospects of LNP-mediated delivery of inhaled therapeutics for respiratory diseases. Full article

(This article belongs to the Special Issue Advances in Nanomedicine for Disease Treatment and Diagnosis)

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16 pages, 1390 KiB

Open AccessEditor’s ChoiceReview

Lipid-Based Drug Delivery Systems for Diseases Managements

by Douweh Leyla Gbian and Abdelwahab Omri

Biomedicines 2022, 10(9), 2137; https://doi.org/10.3390/biomedicines10092137 - 31 Aug 2022

Cited by 14 | Viewed by 3122

Abstract

Liposomes are tiny lipid-based vesicles composed of one or more lipid bilayers, which facilitate the encapsulation of hydrophilic, lipophilic, and amphiphilic biological active agents. The description of the physicochemical properties, formulation methods, characteristics, mechanisms of action, and large-scale manufacturing of liposomes as delivery [...] Read more.

Liposomes are tiny lipid-based vesicles composed of one or more lipid bilayers, which facilitate the encapsulation of hydrophilic, lipophilic, and amphiphilic biological active agents. The description of the physicochemical properties, formulation methods, characteristics, mechanisms of action, and large-scale manufacturing of liposomes as delivery systems are deeply discussed. The benefits, toxicity, and limitations of the use of liposomes in pharmacotherapeutics including in diagnostics, brain targeting, eye and cancer diseases, and in infections are provided. The experimental approaches that may reduce, or even bypass, the use of liposomal drug drawbacks is described. The application of liposomes in the treatment of numerous diseases is discussed. Full article

(This article belongs to the Special Issue Advances in Nanomedicine for Disease Treatment and Diagnosis)

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20 pages, 1201 KiB

Open AccessReview

Macrophage-Derived Extracellular Vesicles: A Promising Tool for Personalized Cancer Therapy

by Antonella Barone, Nicola d’Avanzo, Maria Chiara Cristiano, Donatella Paolino and Massimo Fresta

Biomedicines 2022, 10(6), 1252; https://doi.org/10.3390/biomedicines10061252 - 27 May 2022

Cited by 10 | Viewed by 3335

Abstract

The incidence of cancer is increasing dramatically, affecting all ages of the population and reaching an ever higher worldwide mortality rate. The lack of therapies’ efficacy is due to several factors such as a delay in diagnosis, tumor regrowth after surgical resection and [...] Read more.

The incidence of cancer is increasing dramatically, affecting all ages of the population and reaching an ever higher worldwide mortality rate. The lack of therapies’ efficacy is due to several factors such as a delay in diagnosis, tumor regrowth after surgical resection and the occurrence of multidrug resistance (MDR). Tumor-associated immune cells and the tumor microenvironment (TME) deeply affect the tumor’s progression, leading to several physicochemical changes compared to physiological conditions. In this scenario, macrophages play a crucial role, participating both in tumor suppression or progression based on the polarization of onco-suppressive M1 or pro-oncogenic M2 phenotypes. Moreover, much evidence supports the pivotal role of macrophage-derived extracellular vesicles (EVs) as mediators in TME, because of their ability to shuttle the cell–cell and organ–cell communications, by delivering nucleic acids and proteins. EVs are lipid-based nanosystems with a broad size range distribution, which reflect a similar composition of native parent cells, thus providing a natural selectivity towards target sites. In this review, we discuss the impact of macrophage-derived EVs in the cancer’s fate as well as their potential implications for the development of personalized anticancer nanomedicine. Full article

(This article belongs to the Special Issue Advances in Nanomedicine for Disease Treatment and Diagnosis)

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13 pages, 2345 KiB

Open AccessReview

Nucleic Acid Aptamers in Nanotechnology

by Valentina V. Sinitsyna and Alexandre A. Vetcher

Biomedicines 2022, 10(5), 1079; https://doi.org/10.3390/biomedicines10051079 - 06 May 2022

Cited by 7 | Viewed by 2021

Abstract

Nucleic Acid (NA) aptamers are oligonucleotides. They are unique due to their secondary and tertiary structure; namely, the secondary structure defines the tertiary one by means of affinity and specificity. Our review is devoted only to DNA and RNA aptamers, since the majority [...] Read more.

Nucleic Acid (NA) aptamers are oligonucleotides. They are unique due to their secondary and tertiary structure; namely, the secondary structure defines the tertiary one by means of affinity and specificity. Our review is devoted only to DNA and RNA aptamers, since the majority of achievements in this direction were obtained with their application. NA aptamers can be used as macromolecular devices and consist of short single-stranded molecules, which adopt unique three-dimensional structures due to the interaction of complementary parts of the chain and stacking interactions. The review is devoted to the recent nanotechnological advances in NA aptamers application. Full article

(This article belongs to the Special Issue Advances in Nanomedicine for Disease Treatment and Diagnosis)

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