Nanocarriers For Drug Delivery Research Articles

Engineering Nanomedicine for Non-Viral RNA-Based Gene Therapy of Glioblastoma.

Glioblastoma multiforme (GBM) is the most common type of malignant tumor of the central nervous system, characterized by aggressiveness, genetic instability, heterogenesis, and unpredictable clinical behavior. Disappointing results from the current clinical therapeutic methods have fueled a search for new therapeutic targets and treatment modalities. GBM is characterized by various genetic alterations, and RNA-based gene therapy has raised particular attention in GBM therapy. Here, we review the recent advances in engineered non-viral nanocarriers for RNA drug delivery to treat GBM. Therapeutic strategies concerning the brain-targeted delivery of various RNA drugs involving siRNA, microRNA, mRNA, ASO, and short-length RNA and the therapeutical mechanisms of these drugs to tackle the challenges of chemo-/radiotherapy resistance, recurrence, and incurable stem cell-like tumor cells of GBM are herein outlined. We also highlight the progress, prospects, and remaining challenges of non-viral nanocarriers-mediated RNA-based gene therapy.

Folate-mediated Transport of Nanoparticles across the Placenta.

In this study, a prototype of a targeted nanocarrier for drug delivery for prenatal therapy of the developing fetus was developed and examined in vitro and ex vivo. The folate transport mechanism in the human placenta was utilized as a possible pathway for the transplacental delivery of targeted nanoparticles. Several types of folic acid-decorated polymeric nanoparticles were synthesized and characterized. During transport studies of targeted and non-targeted fluorescent nanoparticles across the placental barrier, the apparent permeability values, uptake, transfer indices, and distribution in placental tissue were determined. The nanoparticles had no effect on BeWo b30 cell viability. In vitro, studies showed significantly higher apparent permeability of the targeted nanoparticles across the cell monolayers as compared to the nontargeted nanoparticles (Pe = 5.92 ± 1.44 ×10-6 cm/s for PLGA-PEG-FA vs. 1.26 ± 0.31 ×10-6 cm/s for PLGA-PEG, P < 0.05), and the transport of the targeted nanoparticles was significantly inhibited by excess folate. Ex vivo placental perfusion showed significantly greater accumulation of the targeted nanoparticles in the placental tissue (4.31 ± 0.91%/g for PLGA-PEG-FA vs. 2.07 ± 0.26%/g for PLGA-PEG). The data obtained suggested different mechanisms for the uptake and transplacental transfer of targeted versus nontargeted nanoparticles. This targeted nanoformulation may be a promising strategy for fetal drug therapy.

Overcoming Endosomal Escape Barriers in Gene Drug Delivery Using De Novo Designed pH-Responsive Peptides.

A major challenge in using nanocarriers for intracellular drug delivery is their restricted capacity to escape from endosomes into the cytosol. Here, we significantly enhance the drug delivery efficiency by accurately predicting and regulating the transition pH (pH0) of peptides to modulate their endosomal escape capability. Moreover, by inverting the chirality of the peptide carriers, we could further enhance their ability to deliver nucleic acid drugs as well as antitumor drugs. The resulting peptide carriers exhibit versatility in transfecting various cell types with a high efficiency of up to 90% by using siRNA, pDNA, and mRNA. In vivo antitumor experiments demonstrate a tumor growth inhibition of 83.4% using the peptide. This research offers a potent method for the rapid development of peptide vectors with exceptional transfection efficiencies for diverse pathophysiological indications.

Molecular Bottlebrushes as Emerging Nanocarriers: Material Design and Biomedical Application.

As a unique unimolecular nanoobject, molecular bottlebrushes (MBBs) have attracted great interest from researchers in nanocarriers attributed to their defined structure, size, and shape. MBBs with various architectures have been proposed and constructed with well-defined domains for loading "cargos", including core, shell, and periphery functional groups. Compared with nanomaterials based on self-assembly, MBBs have lots of advantages, including facile synthesis, flexible compositions, favorable stability, and tunable size and shape, that make them a promising nanoplatform for various applications. This paper summarizes the recent progress during the past decade, with a focus on developments within the last five years in the synthesis of MBBs with different architectures, and uses them as nanocarriers in drug delivery, biological imaging, and other emerging applications.

Polysaccharides as a Hydrophilic Building Block of Amphiphilic Block Copolymers for the Conception of Nanocarriers.

Polysaccharides are gaining increasing attention for their relevance in the production of sustainable materials. In the domain of biomaterials, polysaccharides play an important role as hydrophilic components in the design of amphiphilic block copolymers for the development of drug delivery systems, in particular nanocarriers due to their outstanding biocompatibility, biodegradability, and structural versatility. The presence of a reducing end in polysaccharide chains allows for the synthesis of polysaccharide-based block copolymers. Compared with polysaccharide-based graft copolymers, the structure of block copolymers can be more precisely controlled. In this review, the synthesis methods of polysaccharide-based amphiphilic block copolymers are discussed in detail, taking into consideration the structural characteristics of polysaccharides. Various synthetic approaches, including reductive amination, oxime ligation, and other chain-end modification reactions, are explored. This review also focuses on the advantages of polysaccharides as hydrophilic blocks in polymeric nanocarriers. The structure and unique properties of different polysaccharides such as cellulose, hyaluronic acid, chitosan, alginate, and dextran are described along with examples of their applications as hydrophilic segments in the synthesis of amphiphilic copolymers to construct nanocarriers for sustained drug delivery.

Nanodiamonds: A Cutting-Edge Approach to Enhancing Biomedical Therapies and Diagnostics in Biosensing.

Nanodiamonds (NDs) have garnered attention in the field of nanomedicine due to their unique properties. This review offers a comprehensive overview of NDs synthesis methods, properties, and their uses in biomedical applications. Various synthesis techniques, such as detonation, high-pressure, high-temperature, and chemical vapor deposition, offer distinct advantages in tailoring NDs' size, shape, and surface properties. Surface modification methods further enhance NDs' biocompatibility and enable the attachment of bioactive molecules, expanding their applicability in biological systems. NDs serve as promising nanocarriers for drug delivery, showcasing biocompatibility and the ability to encapsulate therapeutic agents for targeted delivery. Additionally, NDs demonstrate potential in cancer treatment through hyperthermic therapy and vaccine enhancement for improved immune responses. Functionalization of NDs facilitates their utilization in biosensors for sensitive biomolecule detection, aiding in precise diagnostics and rapid detection of infectious diseases. This review underscores the multifaceted role of NDs in advancing biomedical applications. By synthesizing NDs through various methods and modifying their surfaces, researchers can tailor their properties for specific biomedical needs. The ability of NDs to serve as efficient drug delivery vehicles holds promise for targeted therapy, while their applications in hyperthermic therapy and vaccine enhancement offer innovative approaches to cancer treatment and immunization. Furthermore, the integration of NDs into biosensors enhances diagnostic capabilities, enabling rapid and sensitive detection of biomolecules and infectious diseases. Overall, the diverse functionalities of NDs underscore their potential as valuable tools in nanomedicine, paving the way for advancements in healthcare and biotechnology.

Sol-gel synthesis, physicochemical characteristics and in vitro pH-responsive metformin drug release of uniformly polydopamine coated mesoporous silica nanospheres

A recent attention has been paid to the repurposing potential of metformin drug for cancer chemotherapy. Herein, pH-responsive metformin drug delivery nanocarriers were achieved using sol-gel synthesized mesoporous silica nanospheres (MSN) uniformly coated with polydopamine (PDA) shell. The PDA coating shell around the MSN surface was in situ formed through oxidative self-polymerization of dopamine monomers in an alkaline solution at room temperature. The microstructure, structural and textural characteristics of PDA@MSN were examined and compared to uncoated MSN. Furthermore, PDA coated metformin (MET) drug-loaded MSN were used to study the pH-responsive MET drug release behaviour under neutral and acidic conditions. The in vitro release test showed that the PDA coating shell not only protects MET drug leakage under normal physiological conditions (pH 7.4) but also allows for its controlled/sustained release in acidic conditions (pH 4.5 and pH 5.5) which closely mimic the intracellular acidity (pH 4.5–5.5) of endosomes/lysosomes formed around drug-loaded nanocarriers after their endocytosis by cancer cells.

The capability of pure and modified boron carbide nanosheet as a nanocarrier for dacarbazine anticancer drug delivery: DFT study

The capability of pure and modified boron carbide nanosheet as a nanocarrier for dacarbazine anticancer drug delivery: DFT study

Biobased Nanomaterials: Pioneering Innovations for Biomedical Advancements.

The purpose of this review article is to provide a complete overview of the fastdeveloping topic of biobased nanomaterials and the various uses that they have. An extensive study into the utilization of biological resources for nanotechnology has been motivated by the growing demand for materials that are both sustainable and favorable to the environment. In this review, the different uses of biobased nanomaterials across a variety of fields are investigated. When it comes to drug delivery systems, biosensors, nanocarriers, and catalysts, biobased nanomaterials are interesting choices because of their unique qualities. These properties include biocompatibility, programmable surface chemistry, and inherent functionality. Also, in the biomedical field, biobased nanomaterials offer promising prospects for revolutionizing medical diagnostics and therapies. Their biocompatibility, tunable surface chemistry, and inherent functionalities make them attractive candidates for applications such as targeted drug delivery, imaging contrast agents, and tissue engineering scaffolds. In addition, the study discusses the current difficulties and potential future developments in the industry, emphasizing the necessity of interdisciplinary collaboration and ongoing innovation. The incorporation of nanomaterials derived from biological sources into conventional applications holds tremendous potential for the advancement of sustainable development and provides solutions to global concerns. For the purpose of providing researchers, scientists, and professionals with a complete grasp of the synthesis, characterization, and applications of biobased nanomaterials, the purpose of this review is to serve as a helpful resource.

INFLUENCE OF TIME AND TEMPERATURE IN THE MICROWAVE-ASSISTED HYDROTHERMAL TREATMENT OF MAGNETITE NANOPARTICLES

Magnetite is an iron oxide that has been extensively investigated for its utilization in the development of drug delivery nanocarriers. Generally, magnetite nanoparticles are obtained through the chemical route of co-precipitation. However, since the outcome properties of the resulted nanoparticles are limited in terms of possibility to control the size and size distribution and to ensure the reproducibility of the synthesis process, unconventional synthesis routes are constantly investigated. Specifically, the microwave-assisted hydrothermal method represents an alternative with tremendous potential owing to the possibility of varying the treatment parameters, i.e., pressure, temperature, time. Thus, the present study aimed to investigate the influence of time and temperature upon the structural and physico-chemical properties of magnetite nanoparticles.

Multifunctionalized Carbon Dots as an Active Nanocarrier for Drug Delivery to the Glioblastoma Cell Line.

Nanoparticle-based nanocarriers represent a viable alternative to conventional direct administration in cancer cells. This advanced approach employs the use of nanotechnology to transport therapeutic agents directly to cancer cells, thereby reducing the risk of damage to healthy cells and enhancing the efficacy of treatment. By approving nanoparticle-based nanocarriers, the potential for targeted, effective treatment is greatly increased. The so-called carbon-based nanoparticles, or carbon dots, have been hydrothermally prepared and initiated by a polymerization process. We synthesized and characterized nanoparticles of 2-acrylamido-2-methylpropanesulfonic acid, which showed biocompatibility with glioblastoma cells, and further, we tested them as a carrier for the drug riluzole. The obtained nanoparticles have been extensively characterized by techniques to obtain the exact composition of their surface by using Fourier transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS), and nuclear magnetic resonance (NMR) spectroscopy, as well as cryo-transmission electron microscopy. We found that the surface of the synthesized nanoparticles (NPs) is covered mainly by sulfonated, carboxylic, and substituted amide groups. These functional groups make them suitable as carriers for drug delivery in cancer cells. Specifically, we have successfully utilized the NPs as a delivery system for the drug riluzole, which has shown efficacy in treating glioblastoma cancer cells. The effect of nanoparticles as carriers for the riluzole system on glioblastoma cells was studied using live-cell synchrotron-based FTIR microspectroscopy to monitor in situ biochemical changes. After applying nanoparticles as nanocarriers, we have observed changes in all biomacromolecules, including the nucleic acids and protein conformation. These findings provide a strong foundation for further exploration into the development of targeted treatments for glioblastoma.

Recent Advances in Nanomedicine for Ocular Fundus Neovascularization Disease Management.

As an indispensable part of the human sensory system, visual acuity may be impaired and even develop into irreversible blindness due to various ocular pathologies. Among ocular diseases, fundus neovascularization diseases (FNDs) are prominent etiologies of visual impairment worldwide. Intravitreal injection of anti-vascular endothelial growth factor drugs remains the primary therapy but is hurdled by common complications and incomplete potency. To renovate the current therapeutic modalities, nanomedicine emerged as the times required, which is endowed with advanced capabilities, able to fulfill the effective ocular fundus drug delivery and achieve precise drug release control, thus further improving the therapeutic effect. This review provides a comprehensive summary of advances in nanomedicine for FND management from state-of-the-art studies. First, the current therapeutic modalities for FNDs are thoroughly introduced, focusing on the key challenges of ocular fundus drug delivery. Second, nanocarriers are comprehensively reviewed for ocular posterior drug delivery based on the nanostructures: polymer-based nanocarriers, lipid-based nanocarriers, and inorganic nanoparticles. Thirdly, the characteristics of the fundus microenvironment, their pathological changes during FNDs, and corresponding strategies for constructing smart nanocarriers are elaborated. Furthermore, the challenges and prospects of nanomedicine for FND management are thoroughly discussed.

Advances in microscopy characterization techniques for lipid nanocarriers in drug delivery: a comprehensive review.

This review paper provides an in-depth analysis of the significance of lipid nanocarriers in drug delivery and the crucial role of characterization techniques. It explores various types of lipid nanocarriers and their applications, emphasizing the importance of microscopy-based characterization methods such as light microscopy, confocal microscopy, transmission electron microscopy (TEM), scanning electron microscopy (SEM), and atomic force microscopy (AFM). The paper also delves into sample preparation, quantitative analysis, challenges, and future directions in the field. The review concludes by underlining the pivotal role of microscopy-based characterization in advancing lipid nanocarrier research and drug delivery technologies.

Bio-study: Modeling of natural nanomolecules as a nanocarrier surface for antioxidant and glucose biosensor

The nature of nano molecules as a self-assembled nanocomposite surface depends on the nanoparticles of sodium butyrate, cellulose, and pycnogenol; the synthesis is achieved via precipitation and grinding methods. The excellent functionalized surface of nanocomposite (NCP) enables the loading of the selected drugs, where the efficiency of the NCP surface arrived at 92.2 %. The electrochemical behavior emphasized the success of a functionalized NCP surface for incorporation with drugs for the drug delivery system, the results of cytotoxicity detect the effect of NCP on the mouse normal liver (BNL) cells, where the high and low concentrations on the BNL cells have a safe dose. Cell viability with BNL cells was reported at 101.8 % with10 μL and 100.12 % with 100 μL, the interaction between the NCP and the human serum albumin (HSA) at room temperature. The low interaction rate with the glutamate and increased binding with the oxidized glutathione disulfide (GSSG) and reduced glutathione (SGH) reflect the antioxidant activity of NCP. The strong binding of NCP with biomolecules such as glucose is referred to as the biosensor property. The results recommend that NCP is an excellent nanocarrier for drug delivery and glucose biosensors for diabetes.

Amino-Acid-Encoded Bioinspired Supramolecular Self-Assembly of Multimorphological Nanocarriers.

Supramolecular self-assembly has emerged as an efficient tool to construct well-organized nanostructures for biomedical applications by small organic molecules. However, the physicochemical properties of self-assembled nanoarchitectures are greatly influenced by their morphologies, mechanical properties, and working mechanisms, making it challenging to design and screen ideal building blocks. Herein, using a biocompatible firefly-sourced click reaction between the cyano group of 2-cyano-benzothiazole (CBT) and the 1,2-aminothiol group of cysteine (Cys), an amino-acid-encoded supramolecular self-assembly platform Cys(SEt)-X-CBT (X represents any amino acid) is developed to incorporate both covalent and noncovalent interactions for building diverse morphologies of nanostructures with bioinspired response mechanism, providing a convenient and rapid strategy to construct site-specific nanocarriers for drug delivery, cell imaging, and enzyme encapsulation. Additionally, it is worth noting that the biodegradation of Cys(SEt)-X-CBT generated nanocarriers can be easily tracked via bioluminescence imaging. By caging either the thiol or amino groups in Cys with other stimulus-responsive sites and modifying X with probes or drugs, a variety of multi-morphological and multifunctional nanomedicines can be readily prepared for a wide range of biomedical applications.

The Emerging Roles of Nanocarrier Drug Delivery System in Treatment of Intervertebral Disc Degeneration-Current Knowledge, Hot Spots, Challenges and Future Perspectives.

Low back pain (LBP) is a common condition that has substantial consequences on individuals and society, both socially and economically. The primary contributor to LBP is often identified as intervertebral disc degeneration (IVDD), which worsens and leads to significant spinal problems. The conventional treatment approach for IVDD involves physiotherapy, drug therapy for pain management, and, in severe cases, surgery. However, none of these treatments address the underlying cause of the condition, meaning that they cannot fundamentally reverse IVDD or restore the mechanical function of the spine. Nanotechnology and regenerative medicine have made significant advancements in the field of healthcare, particularly in the area of nanodrug delivery systems (NDDSs). These approaches have demonstrated significant potential in enhancing the efficacy of IVDD treatments by providing benefits such as high biocompatibility, biodegradability, precise drug delivery to targeted areas, prolonged drug release, and improved therapeutic results. The advancements in different NDDSs designed for delivering various genes, cells, proteins and therapeutic drugs have opened up new opportunities for effectively addressing IVDD. This comprehensive review provides a consolidated overview of the recent advancements in the use of NDDSs for the treatment of IVDD. It emphasizes the potential of these systems in overcoming the challenges associated with this condition. Meanwhile, the insights and ideas presented in this review aim to contribute to the advancement of precise IVDD treatment using NDDSs.

Degradable Polymer-Based Nanoassemblies for Precise Targeting and Drug Delivery to Breast Cancer Cells without Affecting Normal Healthy Cells.

Stimuli-responsive amphiphilic polymers are known to be precursors to forming promising nanoarchitectonics with tunable properties for application in biomedical sciences. Currently, self-immolative polymers are widely recognized as an emerging class of responsive materials with excellent degradability, which is one of the crucial criteria for designing a robust drug delivery vehicle. Here, we design an amphiphilic polyurethane endowed with a redox-responsive self-immolative linker and a pH-responsive tertiary amine on the backbone, which forms entropy-driven nanoscale supramolecular assemblies (average hydrodynamic diameter ∼110 nm) and is programmed to disassemble in a redox environment (GSH) due to the degradation of the polymer in a self-immolative fashion. The nanoassembly shows efficient drug sequestration and release in a controlled manner in response to glutathione (10 mM). The tertiary amine residing on the surface of the nanoassembly becomes protonated in the tumor microenvironment (pH ∼ 6.4-6.8) and generates positively charged nanoassembly (ζ-potential = +36 mV), which enhances the cancer cell-selective cellular uptake. The biological evaluation of the drug-loaded nanoassembly revealed triple-negative breast cancer (MDAMB-231) selective internalization and cell death while shielding normal cells (RBCs or PBMCs) from off-targeting toxicity. We envision that polyurethane with a redox-responsive self-immolative linker might open up new opportunities for a completely degradable polyurethane-based nanocarrier for drug delivery and diagnosis applications.

Construction of Smart DNA-Based Drug Delivery Systems for Cancer Therapy.

Due to the disadvantages of poor targeting, slow action, and low effectiveness of current commonly used cancer treatments, including surgery, chemotherapy, and radiotherapy, researchers have turned to DNA as a biomaterial for constructing drug delivery nanocarriers. DNA is favored for its biocompatibility and programmability. In order to overcome the limitations associated with traditional drug delivery systems (DDSs), researchers have developed smart-responsive DNA DDSs that can control drug release in response to specific physical or chemical stimuli at targeted sites. In this review, a summary of multiple targeted ligand structures is provided, various shapes of stable DNA nanomaterials, and different stimuli-responsive drug release strategies in DNA DDSs. Specifically, targeted cell recognition, in vivo stable transport, and controlled drug release of smart DDSs are focused. Finally, the further development prospects and challenges of clinical application of DNA nanomaterials in the field of smart drug delivery are discussed. The objective of this review is to enhance researchers' comprehension regarding the potential application of DNA nanomaterials in precision drug delivery, with the aim of expediting the clinical implementation of intelligent DDSs.

An Overview of Polymeric Nanoplatforms to Deliver Veterinary Antimicrobials.

There is an urgent need to find new solutions for the global dilemma of increasing antibiotic resistance in humans and animals. Modifying the performance of existing antibiotics using the nanocarrier drug delivery system (DDS) is a good option considering economic costs, labor costs, and time investment compared to the development of new antibiotics. Numerous studies on nanomedicine carriers that can be used for humans are available in the literature, but relatively few studies have been reported specifically for veterinary pharmaceutical products. Polymer-based nano-DDS are becoming a research hotspot in the pharmaceutical industry owing to their advantages, such as stability and modifiability. This review presents current research progress on polymer-based nanodelivery systems for veterinary antimicrobial drugs, focusing on the role of polymeric materials in enhancing drug performance. The use of polymer-based nanoformulations improves treatment compliance in livestock and companion animals, thereby reducing the workload of managers. Although promising advances have been made, many obstacles remain to be addressed before nanoformulations can be used in a clinical setting. Some crucial issues currently facing this field, including toxicity, quality control, and mass production, are discussed in this review. With the continuous optimization of nanotechnology, polymer-based DDS has shown its potential in reducing antibiotic resistance to veterinary medicines.

Transforming native exosomes to engineered drug vehicles: A smart solution to modern cancer theranostics.

Exosomes have been the hidden treasure of the cell in terms of cellular interactions, transportation and therapy. The native exosomes (NEx) secreted by the parent cells hold promising aspects in cancer diagnosis and therapy. NEx has low immunogenicity, high biocompatibility, low toxicity and high stability which enables them to be an ideal prognostic biomarker in cancer diagnosis. However, due to heterogeneity, NEx lacks specificity and accuracy to be used as therapeutic drug delivery vehicle in cancer therapy. Transforming these NEx with their innate structure and multiple receptors to engineered exosomes (EEx) can provide better opportunities in the field of cancer theranostics. The surface of the NEx exhibits numeric receptors which can be modified to pave the direction of its therapeutic drug delivery in cancer therapy. Through surface membrane, EEx can be modified with increased drug loading potentiality and higher target specificity to act as a therapeutic nanocarrier for drug delivery. This review provides insights into promising aspects of NEx as a prognostic biomarker and drug delivery tool along with its need for the transformation to EEx in cancer theranostics. We have also highlighted different methods associated with NEx transformations, their nano-bio interaction with recipient cells and major challenges of EEx for clinical application in cancer theranostics.