Nanoparticulate Delivery Systems Research Articles

Synthesis of novel coumarin-triazole hybrids and first evaluation of the 4-phenyl substituted hybrid loaded PLGA nanoparticles delivery system to the anticancer activity

Despite the discovery of many chemotherapeutic drugs that prevent uncontrolled cell division processes in the last century, many studies are still being carried out to develop drugs with higher anticancer efficacy and lower level of side effects. Herein, we designed, synthesized, and characterized six novel coumarin-triazole hybrids, and evaluated for anticancer activity of the one with the highest potential against the breast cancer cell line, MCF-7 and human cervical cancer cell line, human cervical adenocarcinoma (HeLa). Compound 21 which was the coumarin derivative including phenyl substituent with the lowest IC50 value displayed the highest cytotoxicity against the studied cancer cell line. Furthermore, the potential use of poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) prepared by the emulsifying solvent evaporation method as a platform for a drug delivery system was studied on a selected coumarin derivative 21. This coumarin derivative-loaded PLGA NPs were produced with an average size of 225.90 ± 2.96 nm, −16.90 ± 0.85 mV zeta potential, and 4.12 ± 0.90% drug loading capacity. The obtained 21-loaded PLGA nanoparticles were analyzed spectroscopically and microscopically with FT-IR, UV–vis, and scanning electron microscopy as well as thermogravimetric analysis, Raman, and x-ray diffraction. The in vitro release of 21 from the nanoparticles exhibited a controlled release profile just over one month following a burst release in the initial six hours and in addition to this a total release ratio of %50 and %85 were obtained at pH 7.4 and 5.5, respectively. 21-loaded PLGA nanoparticles displayed remarkably effective anticancer activity than 21. The IC50 values were determined as IC50 (21-loaded PLGA nanoparticles): 0.42 ± 0.01 mg ml−1 and IC50 (free 21 molecule): 5.74 ± 3.82 mg ml−1 against MCF-7 cells, and as IC50 (21-loaded PLGA nanoparticles): 0.77 ± 0.12 mg ml−1 and IC50 (free 21 molecule): 1.32 ± 0.31 mg ml−1 against HeLa cells after the incubation period of 24 h. Our findings indicated that triazole-substituted coumarins may be used as an anticancer agent by integrating them into a polymeric drug delivery system providing improved drug loading and effective controlled drug release.

Nanoencapsulation of Colchicum speciosum for Alleviating Lower Back Pain

Abstract: This review focuses on the use of Colchicum species that have been capsuled to treat lower back pain. Low levels of physical activity produce atypical spinal loading, which increases the risk of discomfort and damage. Acetylcholine (AChE inhibitors acetylcholinesterase AChE-I) has a crucial role in the development of amyloid- plaques, one of the disease's main pathogenic processes, and in boosting psychological function. To increase the natural preservatives in food, research on the encapsulation of phytochemicals has been employed to create nanoparticle delivery systems for a combination of terpenes that have been isolated from plants. For the administration of formulations containing encapsulated plant extracts, dermal and oral routes are used. The current strategies of encapsulation should be enhanced, as well as techniques to achieve the goal.

Synergistic Action of Benzyl Isothiocyanate and Sorafenib in a Nanoparticle Delivery System for Enhanced Triple-Negative Breast Cancer Treatment.

Triple-negative breast cancer (TNBC) presents a therapeutic challenge due to its complex pathology and limited treatment options. Addressing this challenge, our study focuses on the effectiveness of combination therapy, which has recently become a critical strategy in cancer treatment, improving therapeutic outcomes and combating drug resistance and metastasis. We explored a novel combination therapy employing Benzyl isothiocyanate (BITC) and Sorafenib (SOR) and their nanoformulation, aiming to enhance therapeutic outcomes against TNBC. Through a series of in vitro assays, we assessed the cytotoxic effects of BITC and SOR, both free and encapsulated. The BITC-SOR-loaded nanoparticles (NPs) were synthesized using an amphiphilic copolymer, which demonstrated a uniform spherical morphology and favorable size distribution. The encapsulation efficiencies, as well as the sustained release profiles at varied pH levels, were quantified, revealing distinct kinetics that were well-modeled by the Korsmeyer-Peppas equation. The NP delivery system showed a marked dose-dependent cytotoxicity towards TNBC cells, with an IC50 of 7.8 μM for MDA-MB-231 cells, indicating improved efficacy over free drugs, while exhibiting minimal toxicity toward normal breast cells. Furthermore, the NPs significantly inhibited cell migration and invasion in TNBC models, surpassing the effects of free drugs. These findings underscore the potential of BITC-SOR-NPs as a promising therapeutic approach for TNBC, offering targeted delivery while minimizing systemic toxicity.

Development and characterization of a first-in-class adjustable-dose gene therapy system

IntroductionDespite significant potential, gene therapy has been relegated to the treatment of rare diseases, due in part to an inability to adjust dosage following initial administration. Other significant constraints include cost, specificity, antigenicity, and systemic toxicity of current generation technologies. To overcome these challenges, we developed a first-in-class adjustable-dose gene therapy system, with optimized biocompatibility, localization, durability, and cost. MethodsA lipid nanoparticle (LNP) delivery system was developed and characterized by dynamic light scattering for size, zeta potential, and polydispersity. Cytocompatibility and transfection efficiency were optimized in vitro using primary human adipocytes and preadipocytes. Durability, immunogenicity, and adjustment of expression were evaluated in C57BL/6 and B6 albino mice using in vivo bioluminescence imaging. Biodistribution was assessed by qPCR and immunohistochemistry; therapeutic protein expression was quantified by ELISA. ResultsFollowing LNP optimization, in vitro transfection efficiency of primary human adipocytes reached 81.3 % ± 8.3 % without compromising cytocompatibility. Critical physico-chemical properties of the system (size, zeta potential, polydispersity) remained stable over a broad range of genetic cassette sizes (1,871–6,203 bp). Durable expression was observed in vivo over 6 months, localizing to subcutaneous adipose tissues at the injection site with no detectable transgene in the liver, heart, spleen, or kidney. Gene expression was adjustable using several physical and pharmacological approaches, including cryolipolysis, focused ultrasound, and pharmacologically inducible apoptosis. The ability of transfected adipocytes to express therapeutic transgenes ranging from peptides to antibodies, at potentially clinically relevant levels, was confirmed in vitro and in vivo. ConclusionWe report the development of a novel, low-cost therapeutic platform, designed to enable the replacement of subcutaneously administered protein treatments with a single-injection, adjustable-dose gene therapy.

Cell-mediated nanoparticle delivery systems: towards precision nanomedicine.

Cell-mediated nanoparticle delivery systems (CMNDDs) utilize cells as carriers to deliver the drug-loaded nanoparticles. Unlike the traditional nanoparticle drug delivery approaches, CMNDDs take the advantages of cell characteristics, such as the homing capabilities of stem cells, inflammatory chemotaxis of neutrophils, prolonged blood circulation of red blood cells, and internalization of macrophages. Subsequently, CMNDDs can easily prolong the blood circulation, cross biological barriers, such as the blood-brain barrier and the bone marrow-blood barrier, and rapidly arrive at the diseased areas. Such advantageous properties make CMNDDs promising delivery candidates for precision targeting. In this review, we summarize the recent advances in CMNDDs fabrication and biomedical applications. Specifically, ligand-receptor interactions, non-covalent interactions, covalent interactions, and internalization are commonly applied in constructing CMNDDs in vitro. By hitchhiking cells, such as macrophages, red blood cells, monocytes, neutrophils, and platelets, nanoparticles can be internalized or attached to cells to construct CMNDDs in vivo. Then we highlight the recent application of CMNDDs in treating different diseases, such as cancer, central nervous system disorders, lung diseases, and cardiovascular diseases, with a brief discussion about challenges and future perspectives in the end.

Tumor microenvironment‐responsive hyaluronic acid‐oxaliplatin nanoparticles enhanced tumor cell elimination

AbstractOxaliplatin (OXA) is widely utilized in clinical cancer treatment, however its effectiveness is hindered by drug resistance and severe side effects resulting from non‐targeted delivery and lack of response to the tumor environment. In this research, thiol modified OXA and oligo hyaluronic acid (oHA) were used to developed a redox‐responsive OXA‐SS‐oHA nanoparticle delivery system. The nanoparticles could release oxaliplatin prodrug OXA‐SH through the cleavage of disulfide bonds in response of the abundant GSH in the tumor environment. OXA‐SS‐oHA nanoparticles were stable in aqueous solution for 7 days, and in vitro release experiments showed that the cumulative release of OXA in the absence of GSH was 21%, while in the presence of 10 mM concentration of GSH, the cumulative release was 47%. Additionally, OXA‐SS‐oHA demonstrated greater efficacy in inducing cell death in GSH‐positive cells (MKN45) when compared to GSH‐negative cells (L929). This study provides a novel strategy for the construction of GSH‐stimulated responsive targeted drug delivery systems for cancer therapy.

270 Inducing Neural Maturation and Increasing Survival in SHH Medulloblastoma Using EZH2 Inhibition in a Mouse Model

INTRODUCTION: Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Genetically, MB can be divided into four subgroups of which the SHH subtype histologically shows nodular architecture. Within this nodular architecture, there are islands of mature cells, with more abundant neuropil and a low proliferation rate, scattered among sheets of primitive cells. METHODS: We performed laser capture microdissection followed by whole transcriptome analysis, spatial transcriptomics using Digital Spatial Profiling, whole genome DNA methylation and ChIP-Seq analysis of mature and primitive areas from 8 medulloblastomas. We developed a genetically-engineered mouse model of SHH MB showing spontaneous maturation and lack of maturation with a conditional EZH2 genetic ablation or EZH2 overactivation respectively. Finally, we developed a fucoidan-based nanoparticle drug delivery across the blood brain barrier (BBB) for targeted molecular inhibition. RESULTS: Using whole transcriptome and DNA methylation analysis, we identified ∼120 differentially expressed genes between primitive and mature regions with enrichment for genes regulated by H3K4me3 and H3K27me3. ChIP-Seq analysis showed striking differences in H3K27me3 enrichment between primitive and mature medulloblastoma cells including at the EZH2 locus. Medulloblastoma specific EZH2 genetic ablation resulted in diffuse tumor cell differentiation and prolonged survival in mice (n = 10 per group, log-rank p = 0.01). Conversely, conditional EZH2 (Y641F) activation prevented medulloblastoma differentiation. A fucoidan-based nanoparticle successfully delivered the EZH2 inhibitor (EPZ-6438) across the murine BBB to achieve significant extension of mouse survival (median 70 days compared to 21 days in control mice; *p = 0.01, Mantel-Cox). CONCLUSIONS: Spontaneous maturation of medulloblastoma cells can be induced by inhibition of EZH2. Fucoidan-based nanoparticle delivery systems allows tumor specific targeted delivery across the BBB extending survival in mice.

IRGD-modified erythrocyte membrane biomimetic temozolomide nanodots for the treatment of glioblastoma

The crossing of the blood-brain barrier (BBB) for conventional anticancer drugs is still a big challenge in treating glioma. The biomimetic nanoparticle delivery system has attracted increasing attention and has a promising future for crossing the BBB. Herein, we construct a multifunctional biomimetic nanoplatform using the erythrocyte membrane (EM) with the tumor-penetrating peptide iRGD (CRGDK/RGPD/EC) as a delivery, and the inner core loaded with the chemotherapeutic drug temozolomide (TMZ). The resulting biomimetic nanoparticle has perfect biocompatibility and stealth ability, which will provide more chances to escape the reticuloendothelial system (RES) entrapment, and increase the opportunity to enter the tumor site. Moreover, the decorated iRGD has been extensively used to actively targeting and deliver therapeutic agents across the BBB into glioma tissue. We show that this biomimetic delivery of TMZ with a diameter of 22 nm efficiently slowed the growth of glioblastoma multiforme (GBM) and increased the survival rate of the 30 d from 0% to 100%.

Advances in Nanocarriers for Delivering Therapeutic Agents Against Hepatitis B Virus

Hepatitis B virus (HBV) infection is a crucial public health issue and a major cause of liver disease, such as cirrhosis and hepatocellular carcinoma. At present, orally administered small molecule drugs, such as nucleoside / nucleotide analogues, are recommended as the first‐line treatment for HBV. However, the therapeutic efficacy of these drugs is hindered by off‐target toxicity caused by the whole‐body permeation distribution of these oral drugs. As an emerging drug delivery technology, systemically administered nanocarriers can enhance the aqueous solubility and stability of encapsulated drugs, prolong circulation times, and deliver them efficiently to the liver, showing great promise for increasing the safety and efficacy of small molecule drugs. Furthermore, nanocarriers also accelerate the clinical translation of new therapies, such as nucleic acids and vaccines. This review article highlights the progress of nanoparticle delivery systems in anti‐HBV therapeutics and discusses the opportunities and challenges for the future development of anti‐HBV nanotherapeutics.

Abstract 1368: Novel mRNA encoding anti-PD-L1 monoclonal antibodies for cancer immunotherapy

Abstract The difficulties with antibody-based therapies stem from their steep costs, complex procedures, and contamination risks. We investigate the use of in vitro transcription (IVT) for mRNA production, presenting a novel approach to traditional antibody treatments by promoting internal protein or antibody synthesis. We aim to create innovative mRNA-based anti-PD-L1 antibodies with strong immunotherapeutic effectiveness. The study begins with mouse immunization and hybridoma generation. Immunizing mice with the glycosylated extracellular domain of PD-L1 produces mouse antibodies against human PD-L1. Hybridomas, derived from post-immunization splenocytes, yield monoclonal antibodies screened for PD-L1 binding affinity via flow cytometry. A neutralizing assay identifies 22 antibodies with similar IC50 values and shared binding epitopes. M1, chosen for glycospecificity, affinity, and neutralizing activity, undergoes additional evaluation for the expression and anti-tumor efficacy of mRNA-encoded antibodies. The expression of M1 and atezolizumab antibodies is facilitated through an mRNA-lipid nanoparticles (LNPs) delivery system. Following intravenous administration in mice, sustained serum levels of M1 (ranging from 100 to 700 μg/mL at 24 hours post-injection) are observed. Serum concentrations of M1 and atezolizumab antibody peak at the first timepoint (24 or 48 h) after mRNA-LNP injection, respectively, and then significantly decrease within the next 4 days, with a gradual decline over the next 2 weeks. Conversely, the serum concentrations of M1 or atezolizumab protein decline significantly 24 hours post-injection and consistently stay at a baseline level (t1/2 of 94 and 4 h for M1 mRNA-LNP and protein, respectively). This indicates that the injection of encoded mRNA in mice can stably and continuously express antibodies.Administering Atezolizumab mRNA-LNP through two intravenous injections leads to a significant decrease in MC38 tumor growth, exhibiting a dose-dependent effect (TGI% = 8.1, 43.1, and 62.8 for doses of 0.2, 0.6, and 1 mg/kg, respectively). A complete tumor regression was observed up to day 19 following injection with a 2 mg/kg dose of mRNA-LNP (TGI% = 90.8%). Remarkably, a 3 mg/kg dose of atezolizumab antibody demonstrates a similar reduction in tumor growth as 0.6 mg/kg of the mRNA-LNP formulation in this model. In conclusion, this research underscores the potential of LNP-formulated mRNA as a transformative approach, converting the human body into a site for the continuous, stable expression of antibodies, offering a promising alternative to traditional protein-based therapies for combating cancer. This innovative approach shows promise in overcoming the limitations associated with traditional antibody production and clinical utilization. Citation Format: Ezra Chung, Yong Sik Bong, Renxiang Chen, Michael Zhang, Steven Long, Dong Shen. Novel mRNA encoding anti-PD-L1 monoclonal antibodies for cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1368.

Abstract 5762: Engineering cell membrane nanoparticlesenhance immunotherapy and radiodynamic therapy for lung adenocarcinoma by promoting cGAS-STING and ferroptosis

Abstract Background: Immunotherapy is a promising approach for lung cancer, but its effectiveness is limited by tumor heterogeneity. Nanoparticle-based targeted drug delivery systems offer advantages such as targeted drug-loading capacity, and hypotoxicity, showing great potential in improving therapeutic efficacy. This study introduces a targeted drug delivery strategy based on immune-activating nanoparticles that achieves precise drugs delivery in tumor areas. Consequently, this approach remodels the microenvironment and induces tumor cytotoxicity. Method: In this study, we first constructed a targeted nanoparticle delivery system FP@CC. The vehicle utilized lung adenocarcinoma cell membranes as the outer shell and encapsulated iron-platinum nanoparticles and STING agonist Vadimezan. Then, TREM2 antibodies were conjugated on the outer layer. The structure of FP@CC-aT2 was characterized by HADDF-STEM and its safety was evaluated by hemolysis test. In vitro, its ability to induce death was verified by AM/PI staining, and to induce ferroptosis was detected by C11 assay. Furthermore, we evaluated its antitumor effects in subcutaneous tumor models. The composition of immune cells within the tumor microenvironment was analyzed using flow cytometry. Results: We initially performed HADDF-STEM analysis on the nanoparticle precursor FP/Vad@CC, revealing its uniform sphericity. For security, no significant hemolysis was observed at different concentrations of FP/Vad@CC. Then, the structures of FP/Vad@CC-aT2 and FP/Vad@CC are relatively stable (Fig 1).The number of dead cells significantly increased after deal with FP@CC, and the effect was significantly enhanced when combined with X-ray. Moreover, C11, utilizing to assess the changes in intracellular reactive oxygen species (ROS), found that FP@CC led to a significant increase in ROS, comparable to induction by H2O2. Both could be effectively prevented by ferroptosis inhibitor(Fig 2).In vivo, FP/Vad@CC-aT2 was applied to a subcutaneous tumor model in C57. It exhibited excellent therapeutic efficacy and biocompatibility. Flow cytometry revealed that FP/Vad@CC-aT2 had the anticipated impact on macrophages within the tumor: a significant reduction in CD11high/CD206high cells and opposite in the ratio of M1/M2-like macrophages (Fig 3). Conclusion: This study developed a targeted drug delivery strategy, FP/Vad@CC-aT2, to improve the tumor microenvironment (TME). We conducted preliminary experiments in vitro and in vivo to validate its physicochemical properties and tumor inhibitory effects, including the induction of ferroptosis. We assessed its safety in mouse and obtained initial evidence of FP/Vad@CC-aT2's ability to remodel the subtypes of macrophage.Moving forward, we will validate its therapeutic and impact on the TME after surgical procedures. Citation Format: Haiyu Zhou, Hongrui Qiu, Shiying Li, Bin Xu, Shengbo Liu, Huili Wang, Hengliang Hou. Engineering cell membrane nanoparticlesenhance immunotherapy and radiodynamic therapy for lung adenocarcinoma by promoting cGAS-STING and ferroptosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5762.

Reproducible Synthesis of Biocompatible Albumin Nanoparticles Designed for Intra-articular Administration of Celecoxib to Treat Osteoarthritis.

Osteoarthritis (OA) is the most common form of arthritis, with intra-articular (IA) delivery of therapeutics being the current best option to treat pain and inflammation. However, IA delivery is challenging due to the rapid clearance of therapeutics from the joint and the need for repeated injections. Thus, there is a need for long-acting delivery systems that increase the drug retention time in joints with the capacity to penetrate OA cartilage. As pharmaceutical utility also demands that this is achieved using biocompatible materials that provide colloidal stability, our aim was to develop a nanoparticle (NP) delivery system loaded with the COX-2 inhibitor celecoxib that can meet these criteria. We devised a reproducible and economical method to synthesize the colloidally stable albumin NPs loaded with celecoxib without the use of any of the following conditions: high temperatures at which albumin denaturation occurs, polymer coatings, oils, Class 1/2 solvents, and chemical protein cross-linkers. The spherical NP suspensions were biocompatible, monodisperse with average diameters of 72 nm (ideal for OA cartilage penetration), and they were stable over 6 months at 4 °C. Moreover, the NPs loaded celecoxib at higher levels than those required for the therapeutic response in arthritic joints. For these reasons, they are the first of their kind. Labeled NPs were internalized by primary human articular chondrocytes cultured from the knee joints of OA patients. The NPs reduced the concentration of inflammatory mediator prostaglandin E2 released by the primaries, an indication of retained bioactivity following NP synthesis. Similar results were observed in lipopolysaccharide-stimulated human THP-1 monocytes. The IA administration of these NPs is expected to avoid side-effects associated with oral administration of celecoxib and to maintain a high local concentration in the knee joint over a sustained period. They are now ready for evaluation by IA administration in animal models of OA.

Context-Responsive Nanoparticle Derived from Synthetic Zwitterionic Ionizable Phospholipids in Targeted CRISPR/Cas9 Therapy for Basal-like Breast Cancer.

The majority of triple negative breast cancers (TNBCs) are basal-like breast cancers (BLBCs), which tend to be more aggressive, proliferate rapidly, and have poor clinical outcomes. A key prognostic biomarker and regulator of BLBC is the Forkhead box C1 (FOXC1) transcription factor. However, because of its functional placement inside the cell nucleus and its structural similarity with other related proteins, targeting FOXC1 for therapeutic benefit, particularly for BLBC, continues to be difficult. We envision targeted nonviral delivery of CRISPR/Cas9 plasmid toward the efficacious knockdown of FOXC1. Keeping in mind the challenges associated with the use of CRISPR/Cas9 in vivo, including off-targeting modifications, and effective release of the cargo, a nanoparticle with context responsive properties can be designed for efficient targeted delivery of CRISPR/Cas9 plasmid. Consequently, we have designed, synthesized, and characterized a zwitterionic amino phospholipid-derived transfecting nanoparticle for delivery of CRISPR/Cas9. The construct becomes positively charged only at low pH, which encourages membrane instability and makes it easier for nanoparticles to exit endosomes. This has enabled effective in vitro and in vivo downregulation of protein expression and genome editing. Following this, we have used EpCAM aptamer to make the system targeted toward BLBC cell lines and to reduce its off-target toxicity. The in vivo efficacy, biodistribution, preliminary pharmacokinetics, and biosafety of the optimized targeted CRISPR nanoplatform is then validated in a rodent xenograft model. Overall, we have attempted to knockout the proto-oncogenic FOXC1 expression in BLBC cases by efficient delivery of CRISPR effectors via a context-responsive nanoparticle delivery system derived from a designer lipid derivative. We believe that the nonviral approach for in vitro and in vivo delivery of CRISPR/Cas9 targeted toward FOXC1, studied herein, will greatly emphasize the therapeutic regimen for BLBC.

Recent advances in nanoparticulate RNA delivery systems

Nanoparticle-based RNA delivery has shown great progress in recent years with the approval of two mRNA vaccines for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and a liver-targeted siRNA therapy. Here, we discuss the preclinical and clinical advancement of new generations of RNA delivery therapies along multiple axes. Improvements in cargo design such as RNA circularization and data-driven untranslated region optimization can drive better mRNA expression. New materials discovery research has driven improved delivery to extrahepatic targets such as the lung and splenic immune cells, which could lead to pulmonary gene therapy and better cancer vaccines, respectively. Other organs and even specific cell types can be targeted for delivery via conjugation of small molecule ligands, antibodies, or peptides to RNA delivery nanoparticles. Moreover, the immune response to any RNA delivery nanoparticle plays a crucial role in determining efficacy. Targeting increased immunogenicity without induction of reactogenic side effects is crucial for vaccines, while minimization of immune response is important for gene therapies. New developments have addressed each of these priorities. Last, we discuss the range of RNA delivery clinical trials targeting diverse organs, cell types, and diseases and suggest some key advances that may play a role in the next wave of therapies.

Abstract A002: MALT1 as a regulator of tumor progression in H3K27-altered diffuse midline glioma

Abstract A002: MALT1 as a regulator of tumor progression in H3K27-altered diffuse midline glioma

Alopecia areata: review of epidemiology, pathophysiology, current treatments and nanoparticulate delivery system.

Alopecia areata (AA) is a kind of alopecia that affects hair folliclesand nails. It typically comes with round patches and is a type of nonscarring hair loss. Various therapies are accessible for the management and treatment of AA, including topical, systemic and injectable modalities. It is a very complex type of autoimmune disease and is identified as round patches of hair loss and may occur at any age. This review paper highlights the epidemiology, clinical features, pathogenesis and new treatment options for AA, with a specific emphasis on nanoparticulate drug-delivery systems. By exploring these innovative treatment approaches, researchers aim to enhance the effectiveness and targeted delivery of therapeutic agents, ultimately improving outcomes for individuals living with AA.

Bacteria-Targeting Nanoparticles with ROS-Responsive Antibiotic Release to Eradicate Biofilms and Drug-Resistant Bacteria in Endophthalmitis.

Bacterial endophthalmitis is an acute progressive visual threatening disease and one of the most important causes of blindness worldwide. Current treatments are unsatisfactory due to the emergence of drug-resistant bacteria and the formation of biofilm. The aim of our research was to construct a novel nano-delivery system with better antimicrobial and antibiofilm effects. This study developed a novel antibiotic nanoparticle delivery system (MXF@UiO-UBI-PEGTK), which is composed of (i) moxifloxacin (MXF)-loaded UiO-66 nanoparticle as the core, (ii) bacteria-targeting peptide ubiquicidin (UBI29-41) immobilized on UiO-66, and (iii) ROS-responsive poly (ethylene glycol)-thioketal (PEG-TK) as the surface shell. Then the important properties of the newly developed delivery system, including biocompatibility, toxicity, release percentage, thermal stability, ability of targeting bacteria, and synergistic antibacterial effects on bacterial biofilms and endophthalmitis, were evaluated. In vitro, MXF@UiO-UBI-PEGTK exhibited significant antibiotic effects including the excellent antibiofilm property against Staphylococcus aureus, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus at high levels of ROS. Moreover, MXF@UiO-UBI-PEGTK demonstrated outstanding efficacy in treating bacterial endophthalmitis in vivo. This novel nanoparticle delivery system with ROS-responsive and bacteria-targeted properties promotes the precise and effective release of drugs and has significant potential for clinical application of treating bacterial endophthalmitis.

Sequential dual-locking strategy using photoactivated Pt(IV)-based metallo-nano prodrug for enhanced chemotherapy and photodynamic efficacy by triggering ferroptosis and macrophage polarization

Selective activation of Pt(IV) prodrugs within tumors has emerged as a promising strategy in tumor treatment. Although progress has been made with photo- and ultrasound-activated Pt(IV) prodrugs, concerns remain over the non-specific activation of photosensitizers (PS) and the potential for phototoxicity and chemical toxicity. In this study, a sequential dual-locked Pt(IV) nano-prodrug that can be activated by both the acidic tumor microenvironment and light was developed. The Pt(IV) prodrug was prepared by conjugating PS-locked Pt(IV) to a polymeric core, which was then chelated with metallo iron to lock its photoactivity and form a metallo-nano prodrug. Under acidic tumor microenvironment conditions, the metallo-nano prodrug undergoes dissociation of iron, triggering a reduction process in oxaliplatin under light irradiation, resulting in the activation of both chemotherapy and photodynamic therapy (PDT). Additionally, the prodrug could induce metallo-triggered ferroptosis and polarization of tumor-associated macrophages (TAM), thereby enhancing tumor inhibition. The dual-lock strategy employed in a nanoparticle delivery system represents an expansion in the application of platinum-based anticancer drugs, making it a promising new direction in cancer treatment.

Current approaches in tissue engineering-based nanotherapeutics for osteosarcoma treatment.

Osteosarcoma (OS) is a malignant bone neoplasm plagued by poor prognosis. Major treatment strategies include chemotherapy, radiotherapy, and surgery. Chemotherapy to treat OS has severe adverse effects due to systemic toxicity to healthy cells. A possible way to overcome the limitation is to utilize nanotechnology. Nanotherapeutics is an emerging approach in treating OS using nanoparticulate drug delivery systems. Surgical resection of OS leaves a critical bone defect requiring medical intervention. Recently, tissue engineered scaffolds have been reported to provide physical support to bone defects and aid multimodal treatment of OS. These scaffolds loaded with nanoparticulate delivery systems could also actively repress tumor growth and aid new bone formation. The rapid developments in nanotherapeutics and bone tissue engineering have paved the way for improved treatment efficacy for OS-related bone defects. This review focuses on current bifunctional nanomaterials-based tissue engineered (NTE) scaffolds that use novel approaches such as magnetic hyperthermia, photodynamic therapy, photothermal therapy, bioceramic and polymeric nanotherapeutics against OS. With further optimization and screening, NTE scaffolds could meet clinical applications for treating OS patients.

A comprehensive review on alpha-lipoic acid delivery by nanoparticles

Alpha-lipoic acid (ALA) has garnered significant attention for its potential therapeutic benefits across a wide spectrum of health conditions. Despite its remarkable antioxidant properties, ALA is hindered by challenges such as low bioavailability, short half-life, and unpleasant odor. To overcome these limitations and enhance ALA's therapeutic efficacy, various nanoparticulate drug delivery systems have been explored. This comprehensive review evaluates the application of different nanoparticulate carriers, including lipid-based nanoparticles (solid lipid nanoparticles, niosomes, liposomes, nanostructured lipid carriers (NLCs), and micelles), nanoemulsions, polymeric nanoparticles (nanocapsules, PEGylated nanoparticles, and polycaprolactone nanoparticles), films, nanofibers, and gold nanoparticles, for ALA delivery. Each nanoparticulate system offers unique advantages, such as improved stability, sustained release, enhanced bioavailability, and targeted delivery. For example, ALA-loaded SLNs demonstrated benefits for skin care products and skin rejuvenation. ALA encapsulated in niosomes showed potential for treating cerebral ischemia, a condition largely linked to stroke. ALA-loaded cationic nanoemulsions showed promise for ophthalmic applications, reducing vascular injuries, and corneal disorders. Coating liposomes with chitosan further enhanced stability and performance, promoting drug absorption through the skin. This review provides a comprehensive overview of the advancements in nanoparticulate delivery systems for ALA, highlighting their potential to overcome the limitations of ALA administration and significantly enhance its therapeutic effectiveness. These innovative approaches hold promise for the development of improved ALA-based treatments across a broad spectrum of health conditions.