Nanocarriers For Drug Delivery Research Articles

Influencing Factors and Stimulus-Sensitivity of Chitosan/Polymethacrylic Acid (CS/PMAA) Nanogels as Nanocarriers

ABSTRACT Nanogel, nanosized hydrogel, can contribute to biomedical and pharmaceutical, especially in drug delivery, due to its enthralling properties. Small size, large surface area, hydrophilicity, and stimulus responsiveness of nanogel ameliorate tissue penetration, drug loading capacity, and targeted drug delivery. The current study prepared nanosized, pH-sensitive, biocompatible, and stable chitosan/polymethacrylic acid (CS/PMAA) based nanogels using MBA as a crosslinker and APS as an initiator. FTIR confirmed the reaction between functional groups to synthesize nanogels sufficiently in a spherical shape, as affirmed by a FESEM. DLS data revealed nanosized particles with a size range of 70–170 nm and a range of 6–13 for polydispersity index (PDI). A study showed that 2% of MBA crosslinker is sufficient to achieve the desired crosslinking in 60 minutes reaction time (RT) with nanogel size ~ 92 nm. Increasing RT from 30 to 80 minutes during nanogel synthesis demonstrated a decrease in nanogel sizes from 186–73 nm. Synthesized nanogels have shown pH sensitivity (stimuli responsiveness) in acidic and alkaline mediums with an increase in particle size in pH-2 (~144 nm) and pH-8 (~280 nm) compared to intermediate pHs. The pH sensitivity of nanogels by changing the size per the suspended medium’s pH is crucial for prolonged systemic circulation and targeted drug delivery. Moreover, nanogels have shown good colloidal stability with zeta potential (ZP) +28 mv in acidic and −38 mv alkaline mediums. DSC and XRD results demonstrated thermal stability and amorphous morphology of nanogels, respectively. BET surface analysis revealed the surface area of nanogels in the range of 65–68 cm2/g with an average pore size of 28–32 nm. In-vitro cytotoxicity in the L-929 cell line by MTT assay established the cell viability (>70%) after 24 hours of incubation, substantiating the non-toxicity and biocompatibility of nanogels as nanocarriers for drug delivery.

Analysis of Structural Changes of pH-Thermo-Responsive Nanoparticles in Polymeric Hydrogels.

The pH- and thermo-responsive behavior of polymeric hydrogels MC-co-MA have been studied in detail using dynamic light scattering DLS, scanning electron microscopy SEM, nuclear magnetic resonance (1H NMR) and rheology to evaluate the conformational changes, swelling-shrinkage, stability, the ability to flow and the diffusion process of nanoparticles at several temperatures. Furthermore, polymeric systems functionalized with acrylic acid MC and acrylamide MA were subjected to a titration process with a calcium chloride CaCl2 solution to analyze its effect on the average particle diameter Dz, polymer structure and the intra- and intermolecular interactions in order to provide a responsive polymer network that can be used as a possible nanocarrier for drug delivery with several benefits. The results confirmed that the structural changes in the sensitive hydrogels are highly dependent on the corresponding critical solution temperature CST of the carboxylic (-COOH) and amide (-CONH2) functional groups and the influence of calcium ions Ca2+ on the formation or breaking of hydrogen bonds, as well as the decrease in electrostatic repulsions generated between the polymer chains contributing to a particle agglomeration phenomenon. The temperature leads to a re-arrangement of the polymer chains, affecting the viscoelastic properties of the hydrogels. In addition, the diffusion coefficients D of nanoparticles were evaluated, showing a closeness among with the morphology, shape, size and temperature, resulting in slower diffusions for larger particles size and, conversely, the diffusion in the medium increasing as the polymer size is reduced. Therefore, the hydrogels exhibited a remarkable response to pH and temperature variations in the environment. During this research, the functionality and behavior of the polymeric nanoparticles were observed under different analysis conditions, which revealed notable structural changes and further demonstrated the nanoparticles promising high potential for drug delivery applications. Hence, these results have sparked significant interest in various scientific, industrial and technological fields.

Strategic Developments in Polymer-Functionalized Liposomes for Targeted Colon Cancer Therapy: An Updated Review of Clinical Trial Data and Future Horizons.

Liposomes, made up of phospholipid bilayers, are efficient nanocarriers for drug delivery because they can encapsulate both hydrophilic and lipophilic drugs. Conventional cancer treatments sometimes involve considerable toxicities and adverse drug reactions (ADRs), which limits their clinical value. Despite liposomes' promise in addressing these concerns, clinical trials have revealed significant limitations, including stability, targeted distribution, and scaling challenges. Recent clinical trials have focused on enhancing liposome formulations to increase therapeutic efficacy while minimizing negative effects. Notably, the approval of liposomal medications like Doxil demonstrates their potential in cancer treatment. However, the intricacy of liposome preparation and the requirement for comprehensive regulatory approval remain substantial impediments. Current clinical trial updates show continued efforts to improve liposome stability, targeting mechanisms, and payload capacity in order to address these issues. The future of liposomal drug delivery in cancer therapy depends on addressing these challenges in order to provide patients with more effective and safer treatment alternatives.

Engineering of dopamine conjugated with bovine serum albumin and zeolite imidazole framework: A promising drug delivery nanocarrier on lung cancer cells

Modern, highly abundant materials called metal-organic structures (MOF) comprise metal ions and organic coordinating molecules and have attracted attention as potential biomedical materials due to their unusual properties. In the present study, the anticancer drug sorafenib (SF) and the Kaempferol (KM) were encapsulated in a nanocomposite made of bovine serum albumin (BA) as the core and pH-dependent zeolitic imidazolate framework-8 (ZIF) coating. To develop a multifunctional nanocarrier, polydopamine, Au3+ chelation, and gallic acid (GL) conjugation were used to build BA@SF@ZIF and BA@SF@ZIF/KM. A variety of characterisation techniques verified the success of the nanocarrier's fabrication. Studies in vitro exhibited that BA@SF@ZIF/DA/GL and BA@SF@ZIF/KM/DA/GL released their respective ligands in a pH-dependent manner due to ZIF-8. These nanocarriers' cytotoxicity and apoptotic effects were measured with the MTT evaluation. Morphological and nuclear damage staining in A549 and H1299 human lung cancer cells. The cytotoxicity investigation displayed that BA@SF@ZIF/DA/GL and BA@SF@ZIF/KM/DA/GL were more efficient than free sorafenib in A549 and H1299 cells with less toxicity in HUVECs. The DNA fragmentation of the cells was assessed by utilizing the comet assay. BA@SF@ZIF/KM/DA/GL increased ROS levels and caused mitochondrial membrane potential and DNA damage, which resulted in apoptosis. Therefore, we believe the developed smart BA@SF@ZIF/KM/DA/GL could be a promising therapeutic approach using sorafenib for lung cancer therapy.

Gelatin-based carbon quantum dot-molecularly imprinted polymer: Safe photoluminescent core-shell nano-carrier for the pH-responsive anticancer drug delivery

This study aims to synthesize a core-shell gelatin-based carbon quantum dot-molecularly imprinted polymer (MIP@g-CQD) via the precipitation free-radical polymerization process using methotrexate (MTX) as a model anticancer template. To investigate the efficiency of the prepared photoluminescent MIP@g-CQD as a pH-responsive nano-carrier, MTX was loaded into MIP@g-CQD by soaking in a drug solution and the release behavior of the loaded drug was evaluated in the necessary pH values (7.4, 5). The successful synthesis of materials was characterized using PL, TEM, FE-SEM, DLS, and FT-IR analyses. Interestingly, the created cavities in the core-shell nano-carriers can interact with the MTX molecules effectively, leading to an increase in the loading capacity. According to the obtained results from Langmuir adsorption isotherms, the imprinting factor was calculated (IF = 4.91). Also, the binding kinetics of MTX revealed the creation of particular recognition sites in the core-shell polymeric network. The MTX-loaded MIP@g-CQD displayed a low rate and limited release at the simulated physiological environment (pH 7.4, 37 °C), but it is increased at tumor tissue (pH 5, 41 °C) conditions, which can lead to long-term and sustained release of MTX in the desired target. This property of MIP@g-CQD could avoid the release of MTX in normal physiological conditions, decreasing the possible side effects of MTX drug. Owing to the existence of amide functional groups in the nano-carrier structure and its negatively charged nature, the MTT assay displayed desirable cytotoxicity against the breast cancer cell line (MCF-7) for the MTX-loaded nano-carrier. According to the obtained results, the prepared safe photoluminescent MIP@g-CQD with appropriate pH-responsivity has a high ability to be applied as an anticancer and bio-detection agent.

Advances in Extracellular-Vesicles-Based Diagnostic and Therapeutic Approaches for Ocular Diseases.

Extracellular vesicles (EVs) are nanoscale membrane vesicles of various sizes that can be secreted by most cells. EVs contain a diverse array of cargo, including RNAs, lipids, proteins, and other molecules with functions of intercellular communication, immune modulation, and regulation of physiological and pathological processes. The biofluids in the eye, including tears, aqueous humor, and vitreous humor, are important sources for EV-based diagnosis of ocular disease. Because the molecular cargos may reflect the biology of their parental cells, EVs in these biofluids, as well as in the blood, have been recognized as promising candidates as biomarkers for early diagnosis of ocular disease. Moreover, EVs have also been used as therapeutics and targeted drug delivery nanocarriers in many ocular disorders because of their low immunogenicity and superior biocompatibility in nature. In this review, we provide an overview of the recent advances in the field of EV-based studies on the diagnosis and therapeutics of ocular disease. We summarized the origins of EVs applied in ocular disease, assessed different methods for EV isolation from ocular biofluid samples, highlighted bioengineering strategies of EVs as drug delivery systems, introduced the latest applications in the diagnosis and treatment of ocular disease, and presented their potential in the current clinical trials. Finally, we briefly discussed the challenges of EV-based studies in ocular disease and some issues of concern for better focusing on clinical translational studies of EVs in the future.

Ionizable Lipid Containing Nanocarriers for Antimicrobial Agent Delivery

Antimicrobial resistance (AMR) poses a global health crisis demanding innovative solutions. Traditional antibiotics, though pivotal over the past century in combating bacterial infections, face diminished efficacy against evolving bacterial defense mechanisms, especially in Gram‐negative strains. This study explores self‐assembled ionizable lipid nanoparticles (LNPs) with the incorporation of two ionizable lipid components (one cationic, one anionic) in nanocarriers for advanced antimicrobial drug delivery of the broad‐spectrum antibiotic Piperacillin (Pip). Incorporating cationic ionizable lipid ALC‐0315, recognized as a functional lipid in the Pfizer‐BioNTech mRNA‐based SARS‐CoV‐2 vaccine, into LNPs allowed mesophase transition, pH responsiveness, and ionization behavior in acidic environments found in sites of bacterial infections, to be studied using synchrotron small angle X‐ray scattering, dynamic light scattering, and a 2‐(p‐toluidino)‐6‐naphthalene sulfonic acid assay. Incorporating another anionic ionizable lipid, oleic acid not only modulates the LNPs’ physicochemical properties, such as size, internal phase nanostructure, and surface charge but also synergistically enhances the antimicrobial potency together with ALC‐0315 with a benefit enhancing permeability and fusion with bacterial membranes. This study introduces a strategy for tailoring ionizable lipid compositions in LNPs, providing a new approach to antimicrobial treatment contributing to the fight against AMR.

Nanotechnology-based Drug Delivery for Alzheimer's and Parkinson's Diseases.

The delivery of drugs to the brain is quite challenging in the treatment of the central nervous system (CNS) diseases due to the blood-brain barrier and the blood-cerebrospinal fluid barrier. However, significant developments in nanomaterials employed by nanoparticle drug-delivery systems have substantial potential to cross or bypass these barriers leading to enhanced therapeutic efficacies. Advances in nanoplatform, nanosystems based on lipids, polymers and inorganic materials have been extensively studied and applied in treating Alzheimer's and Parkinson's diseases. In this review, various types of brain drug delivery nanocarriers are classified, summarized, and their potential as drug delivery systems in Alzheimer's and Parkinson's diseases is discussed. Finally, challenges facing the clinical translation of nanoparticles from bench to bedside are highlighted.

Fabrication of co-delivery liposomal formulation incorporating carmustine and cabazitaxel displays improved cytotoxic potential and induced apoptosis in ovarian cancer cells

Ovarian cancer is the primary cause of death from cancer in female patients. The existing treatments for ovarian cancer are restricted and ineffective in achieving a cure for the disease. To address this issue, we provide a novel approach to treating ovarian cancer by utilizing a liposomal carrier that effectively delivers the chemotherapeutic drugs carmustine (BCNU) and cabazitaxel (CTX). Initially, the combined impact of BCNU and CTX was confirmed, revealing that this impact reaches its maximum at a ratio of 1:2 mol/mol (BCNU/CTX). After that, the BC-Lipo co-delivery system was developed, which has a high capability for loading drugs (97.48% ± 1.14 for BCNU, 86.29% ± 3.03 for CTX). This system also has a sustained release profile and a beneficial long-circulating feature. The accumulation of BC-Lipo in tumors was dramatically enhanced compared to the accumulation of the free drug. Furthermore, BC-Lipo demonstrated similar levels of cytotoxicity to free BCNU and CTX (BCNU/CTX) when tested on HeLa cells in an in vitro model. Biochemical staining methods investigated the cancer cell’s morphological examination. The apoptosis was confirmed by FITC-Annexin-V/PI staining by flow cytometry analysis. In addition, the investigation of fluorescence and protein markers examined the apoptosis mechanistic pathway, and the results indicated that BC-Lipo induced apoptosis due to mitochondrial membrane potential variation. This proof-of-concept study has established the probability of these BCNU-CTX combined treatments as active drug delivery nanocarriers for poorly soluble BCNU and CTX.

Measurements of Spontaneous and External Stimuli Molecular Release Processes from a Single Optically Trapped Poly(lactic-co-glycolic) Acid Microparticle and a Liposome Containing Gold Nanospheres.

We investigated the single particle kinetics of the molecular release processes from two types of microcapsules used as drug delivery systems (DDS): biodegradable poly(lactic-co-glycolic) acid (PLGA) and a light-triggered-degradable liposome encapsulating gold nanospheres (liposome-GNP). To optimize the design of DDS capsules, it is highly desirable to develop a method for real-time monitoring of the release process. Using a combination of optical tweezers and confocal fluorescence microspectroscopy we successfully analyzed a single optically trapped PLGA particle and liposome-GNPs in solution. From temporal decay profiles of the fluorescence intensity, we determined the time constant τ of the release processes. We demonstrated that the release rate of spontaneously degradable microcapsules (PLGA) decreased with increasing size, while conversely, the release rate of external stimuli-degradable microcapsules (liposome-GNPs) increased in proportion to their size. This result is explained by the differences in the disruption mechanisms of the capsules, with PLGA undergoing hydrolysis and the GNPs in the liposome-GNP undergoing a photoacoustic effect under nanosecond pulsed laser irradiation. The present approach offers a way forward to an alternative microanalysis system for single drug delivery nanocarriers.

Application of sphingolipid-based nanocarriers in drug delivery: an overview.

Sphingolipids (SL) are well recognized for their cell signaling through extracellular and intracellular pathways. Based on chemistry different types of SL are biosynthesized in mammalian cells and have specific function incellular activity. SL has an ampiphilic structure with have hydrophobic body attached to the polar head enables their use as a drug delivery agent in the form of nanocarriers. SL-based liposomes can improve the solubility of lipophilic drugs through host and drug complexes and are more stable than conventional liposomal formulations. Preclinical studies of SL nanocarriers are reported on topical delivery, oral delivery, ocular delivery, chemotherapeutic delivery, cardiovascular delivery and Alzheimer's disease. The commercial challenges and patents related to SL nanoformulations are highlighted in this article.

Utilizing engineered extracellular vesicles as delivery vectors in the management of ischemic stroke: a special outlook on mitochondrial delivery.

Ischemic stroke is a secondary cause of mortality worldwide, imposing considerable medical and economic burdens on society. Extracellular vesicles, serving as natural nano-carriers for drug delivery, exhibit excellent biocompatibility in vivo and have significant advantages in the management of ischemic stroke. However, the uncertain distribution and rapid clearance of extracellular vesicles impede their delivery efficiency. By utilizing membrane decoration or by encapsulating therapeutic cargo within extracellular vesicles, their delivery efficacy may be greatly improved. Furthermore, previous studies have indicated that microvesicles, a subset of large-sized extracellular vesicles, can transport mitochondria to neighboring cells, thereby aiding in the restoration of mitochondrial function post-ischemic stroke. Small extracellular vesicles have also demonstrated the capability to transfer mitochondrial components, such as proteins or deoxyribonucleic acid, or their sub-components, for extracellular vesicle-based ischemic stroke therapy. In this review, we undertake a comparative analysis of the isolation techniques employed for extracellular vesicles and present an overview of the current dominant extracellular vesicle modification methodologies. Given the complex facets of treating ischemic stroke, we also delineate various extracellular vesicle modification approaches which are suited to different facets of the treatment process. Moreover, given the burgeoning interest in mitochondrial delivery, we delved into the feasibility and existing research findings on the transportation of mitochondrial fractions or intact mitochondria through small extracellular vesicles and microvesicles to offer a fresh perspective on ischemic stroke therapy.

Metal-Organic Framework: Fabrication of Nano Fluorescent Composite Materials and Treatment of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a common malignant tumor originating from liver cells, characterized by complex pathogenesis and limited treatment options such as surgery, chemotherapy, and transplantation. Cisplatin, an effective chemotherapeutic agent, disrupts cancer cell DNA but is hindered by side effects and the need for controlled sustained release to optimize efficacy. Metal-organic frameworks (MOFs) have emerged as promising nanocarriers for precise local drug delivery, reducing required doses and mitigating side effects of chemotherapeutic drugs, thus offering a potential avenue for hepatocellular carcinoma (HCC) treatment. In this research, a rectangular channel MOF (Rumgay H, Ferlay J, Martel C, Georges D, Ibrahim AS, Zheng R, Wei W, Lemmens VEPP, Soerjomataram I (2022) Global, regional and national burden of primary liver cancer by subtype. Eur J Cancer 161:108-118) carrier was synthesized using ligand L as the organic linker coordinated with Cu(II) and I(I). The MOF's structure and fluorescence properties were characterized. Additionally, to enhance substrate biocompatibility, composite carrier materials were prepared by incorporating polylactic acid (PLA) with 1, utilized for cisplatin loading. To evaluate the inhibitory effect of PLA-1@cisplatin on HCC, HepG-2 and Huh-7 HCC cell lines were treated with varying concentrations of the drug for 48h, and their cell viability was assessed. The results demonstrated a significant dose-dependent reduction in cell viability of both HepG-2 and Huh-7 cells. To explore the potential inhibitory mechanism of PLA-1@cisplatin on HCC, the mRNA levels of GADD45A and NACC1 in HepG-2 and Huh-7 cells post-treatment were measured. GADD45A expression, initially low in HCC cells, was significantly upregulated after drug treatment, while NACC1, typically highly expressed in HCC, showed a significant decrease in mRNA levels with increasing concentrations of PLA-1@cisplatin. These findings indicate that PLA-1@cisplatin effectively upregulates GADD45A expression and downregulates NACC1 expression. Overall, the developed cisplatin-loaded nanoparticle system holds promise for HCC treatment by reducing chemotherapy side effects and enhancing drug efficacy.

Unlocking the potential of microfold cells for enhanced permeation of nanocarriers in oral drug delivery

The therapeutic effects of orally administered nanocarriers depend on their ability to effectively permeate the intestinal mucosa, which is one of the major challenges in oral drug delivery. Microfold cells are specialized enterocytes in the intestinal epithelium known for their high transcytosis abilities. This study aimed to compare and evaluate two targeting approaches using surface modifications of polymer-based nanocarriers, whereas one generally addresses enterocytes, and one is directed explicitly to microfold cells via targeting the sialyl LewisA motif on their surface. We characterized the resulting carriers in terms of size and charge, supplemented by scanning electron microscopy to confirm their structural properties. For predictive biological testing and to assess the intended targeting effect, we implemented two human intestinal in vitro models containing microfold-like cells. Both models were thoroughly characterized prior to permeation studies with the different nanocarriers. Our results demonstrated improved transport for both targeted formulations compared to undecorated carriers in the in vitro models. Notably, there was an enhanced uptake in the presence of microfold-like cells, particularly for the nanocarriers directed by the anti-sialyl LewisA antibody. These findings highlight the potential of microfold cell targeting to improve oral administration of drugs and emphasize the importance of using suitable and well-characterized in vitro models for testing novel drug delivery strategies.

Reversible Light-Triggered Stretching of Small-Molecule Photochromic Organic Nanoparticles.

Functional organic nanomaterials are nowadays largely spread in the field of nanomedicine. In situ modulation of their morphology is thus expected to considerably impact their interactions with the surroundings. In this context, photoswitchable nanoparticles that are manufactured, amenable to extensive disassembling upon illumination in the visible, and reversible reshaping under UV exposure. Such reversibility turns to be strongly impaired for photochromic nanoparticles in close contact with a substrate. In situ atomic force microscopy investigations at the nanoscale actually reveal progressive disintegration of the organic nanoparticles under successive UV-vis cycles of irradiation, in the absence of intrinsic elastic forces. These results point out the dramatic interactions exerted by surfaces on the cohesion of non-covalently bonded organic nanoparticles. They invite to harness such systems, often used as biomarkers, to also serve as photoactivatable drug delivery nanocarriers.

Biocompatible Preparation of Beta-Lactoglobulin/Chondroitin Sulfate Carrier Nanoparticles and Modification of Their Colloidal and Hydropathic Properties by Tween 80.

The electrostatic complexation of the protein beta-lactoglobulin (β-LG) with the anionic polysaccharide chondroitin sulfate (CS) and the subsequent stabilization by thermal treatment were studied to achieve the well-defined nanoparticles (NPs). The formation of the well-defined NPs was obtained at pH 4 with a hydrodynamic radius from 60 to 80 nm. NP aggregation was observed at pH 1.5 because of the loss of the anionic charge of chondroitin sulfate on the surface of the NPs. After thermal treatment, the NPs exhibited stability against a pH increase to pH 7 while a stronger aggregation at pH 1.5 was observed. Core-shell structures were found at pH 7 after thermal treatment, indicating a possible mechanism of partial disintegration. The addition of Tween 80 (T80) before thermal treatment led to the formation of T80 self-assemblies inside the NPs. This caused an increase in the hydrophobicity of the inner and outer surfaces of the NPs as it was observed by fluorescence spectroscopy. The ζ-potential of the complexes and NPs was about -20 mV while the presence of T80 did not affect it. FTIR spectra verified changes of the secondary structure of β-LG in its complexes with CS and T80. The thermally treated NPs exhibited high surface and overall hydrophobicity and stability in high salinity and biocompatible solutions. The thermally treated NPs showed colloidal and physicochemical stability for 1 month, which were enhanced by the addition of T80. Due to the nature of the precursors and their colloidal properties, the NPs are highly promising for applications as biocompatible drug delivery nanocarriers while T80 acts as an agent to modify their properties.

Tailoring Silk Sericin Grafting: Comparing One‐Step and Two‐Step Approaches for PNIPAM/PAMPS Block Nanoparticles

AbstractStructurally defined, protein‐grafted nanoparticles are widely used in various biomedical applications, particularly as intelligent nanocarriers for drug delivery. The integration of synthetic polymers with natural proteins such as silk sericin enhances the functionality and stability of these nanocarriers, making them suitable for targeted and controlled drug release. In this context, an optimized grafting procedure for silk sericin is presented, employing a protein macroinitiator and atom transfer radical polymerization (ATRP). This study aims to elucidate the significance of the grafting process in tailoring the structure of sericin through the chemistry of synthetic grafts. The grafting procedure uses block copolymers of N‐isopropylacrylamide (NIPAM) and 2‐acrylamido‐2‐methylpropanesulfonic acid (AMPS), such as Poly‐(AMPS‐block‐NIPAM)/Poly‐(NIPAM‐block‐AMPS). The procedure employs both one‐step and two‐step synthesis methods to produce a well‐defined, biofunctionalized sericin. Subsequently, sericin‐based nanoparticles are prepared, demonstrating the significance of the optimized procedure. The synthesized products undergo structural analysis using H‐NMR, FTIR‐ATR, XPS, DLS, and zeta potential measurements. In addition, their thermal behavior is assessed using differential scanning calorimetry. To further investigate the prepared nanoparticles, SEM and DLS analyses are conducted. Through synthesis optimization, position and length of each synthetic block is precisely determined, significantly influencing properties of the grafted products and characteristics of the resulting nanoparticles.

Emerging Nanotechnology in Preclinical Pancreatic Cancer Immunotherapy: Driving Towards Clinical Applications.

The high malignant degree and poor prognosis of pancreatic cancer (PC) pose severe challenges to the basic research and clinical translation of next-generation therapies. The rise of immunotherapy has improved the treatment of a variety of solid tumors, while the application in PC is highly restricted by the challenge of immunosuppressive tumor microenvironment. The latest progress of nanotechnology as drug delivery platform and immune adjuvant has improved drug delivery in a variety of disease backgrounds and enhanced tumor therapy based on immunotherapy. Based on the immune loop of PC and the status quo of clinical immunotherapy of tumors, this article discussed and critically analyzed the key transformation difficulties of immunotherapy adaptation to the treatment of PC, and then proposed the rational design strategies of new nanocarriers for drug delivery and immune regulation, especially the design of combined immunotherapy. This review also put forward prospective views on future research directions, so as to provide information for the new means of clinical treatment of PC combined with the next generation of nanotechnology and immunotherapy.

Recent Updates on Nanocarriers for Drug Delivery in Posterior Segment Diseases with Emphasis on Diabetic Retinopathy.

In recent years, various conventional formulations have been used for the treatment and/or management of ocular medical conditions. Diabetic retinopathy, a microvascular disease of the retina, remains the leading cause of visual disability in patients with diabetes. Currently, for treating diabetic retinopathy, only intraocular, intravitreal, periocular injections, and laser photocoagulation are widely used. Frequent administration of these drugs by injections may lead to serious complications, including retinal detachment and endophthalmitis. Although conventional ophthalmic formulations like eye drops, ointments, and suspensions are available globally, these formulations fail to achieve optimum drug therapeutic profile due to immediate nasolacrimal drainage, rapid tearing, and systemic tearing toxicity of the drugs. To achieve better therapeutic outcomes with prolonged release of the therapeutic agents, nano-drug delivery materials have been investigated. These nanocarriers include nanoparticles, solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), dendrimers, nanofibers, in-situ gel, vesicular carriers, niosomes, and mucoadhesive systems, among others. The nanocarriers carry the potential benefits of site-specific delivery and controlled and sustained drug release profile. In the present article, various nanomaterials explored for treating diabetic retinopathy are reviewed.

Development and characterization of magnetic-based biodegradable periodic mesoporous organosilica nanoparticles for enhanced biomedical applications

Herein, magnetic-based biodegradable periodic mesoporous organosilica (BPMO) nanoparticles were successfully synthesized via a co-precipitation method to form a magnetic iron oxide (Fe3O4) core, followed by the condensation of organosilica precursors to produce BPMO shells. The physicochemical properties of the resulting hybrid nanoparticles were evaluated using powder X-ray diffraction, nitrogen adsorption–desorption isotherms, thermogravimetric analysis, Fourier transform infrared spectroscopy, and vibrating sample magnetometry. The synthesized particles exhibited a spherical morphology with an average diameter of approximately 250 nm. A core–shell structure was formed by depositing a 100-nm biodegradable organosilica layer onto the magnetic Fe3O4 cluster, endowing the nanoparticles with both magnetic and biodegradable mesoporous characteristics. Notably, despite the silica coating, the saturation magnetization remained high, reaching 35.8 emu/g, suggesting the potential for using these nanoparticles in magnetic-based biomedical applications. Furthermore, Fe3O4@BPMO nanoparticles were demonstrated to be efficiently uptaken by OVCAR8 ovarian cancer cells and spheroids, indicating that these nanoparticles are promising as magnetic nanocarriers for anti-cancer drug delivery and can be used in magnetic resonance imaging and magnetic hyperthermia.