Multifunctional sericin-based biomineralized nanoplatforms with immunomodulatory and angio/osteo-genic activity for accelerated bone regeneration in periodontitis.

Periodontitis is a chronic inflammation caused by dental plaque. It is characterized by the accumulation of excessive reactive oxygen species (ROS) and inflammatory mediators in the periodontal area. This affects the function of host cells, activates osteoclasts, and destroys periodontal tissue. Treatments such as local debridement or antibiotic therapy for ameliorating the overactive inflammatory microenvironment and repairing periodontal tissues are challenging. This paper reports multifunctional nanoplatforms (Se-CuSrHA@EGCG) based on sericin with ROS-scavenging, immunomodulatory, angiogenic, and osteogenic capabilities. The natural protein sericin, derived from silk cocoons, is used in water/oil emulsification and cross-linking processes to create sericin nanoparticles (Se NPs). Numerous binding sites are present on the surface of Se NPs. Ion-doped hydroxyapatite nanoparticles (Se-CuSrHA NPs) can be constructed using the force between positive and negative charges. After mineralization, an antioxidant coating is formed on the surface using polyethyleneimine (PEI)/epigallocatechin gallate (EGCG). Research conducted both in vitro and in vivo demonstrates that Se-CuSrHA@EGCG NPs can efficiently scavenge ROS, regulate macrophage polarization, increase the secretion of anti-inflammatory cytokines, and balance the immune microenvironment. In addition, Se-CuSrHA@EGCG stimulates angiogenesis, inhibits osteoclasts, and accelerates periodontal tissue repair. Therefore, this is a preferable strategy to accelerate bone regeneration in patients with periodontitis.

H2O2 Self-Supplying CaO2 Nanoplatform Induces Ca2+ Overload Combined with Chemodynamic Therapy to Enhance Cancer Immunotherapy.

Integrating chemodynamic therapy (CDT) with Ca2+ overload offers a potent strategy for enhancing cancer immunotherapy. However, the effectiveness of this approach is significantly constrained by the scarce availability of H2O2 in solid tumors. Here, we engineered a nanoplatform based on CaO2 nanoparticles (NPs) capable of encapsulating curcumin (CUR) and self-supplying H2O2 for synergistic CDT-augmented antitumor immunotherapy (CaO2@CUR@ZIF-Cu, denoted as CCZC). In the acidic tumor microenvironment, CCZC disintegrated to release CUR and copper(II) ions (Cu2+), revealing the core CaO2 NPs. CDT was amplified by escalating hydroxyl radical (•OH) production through a Fenton-like reaction mediated by H2O2 from the hydrolysis of CaO2 NPs. Ca2+ sourced from CaO2 NPs and CUR, an initiator of Ca2+ overload, induced Ca2+ overload in tumor cells, thereby promoting apoptosis. Subsequently, apoptotic tumor cells released tumor-associated antigens and pro-inflammatory cytokines, triggering adaptive immune responses and enhancing antitumor immunotherapy effects. In vivo experiments demonstrated that the intratumoral administration of CCZC displayed significant inhibitory effects, with an inhibition rate of up to 78% on B16-OVA-tumor-bearing mice compared to untreated. Moreover, an elevated proportion of mature dendritic cells were observed in the tumor-draining lymph nodes, along with an increase in cytotoxic T lymphocytes in the spleen. These findings suggest that our engineered nanoplatform effectively curtailed tumor growth via enhanced cancer immunotherapy by synergizing Ca2+ overload and CDT, proposing a novel strategy for synergistic cancer treatment.

Developing Porous Protein Cage Nanoparticles as Cargo-Loadable and Ligand-Displayable Modular Delivery Nanoplatforms.

Protein cage nanoparticles, self-assembled from protein subunits, provide distinct exterior and interior spaces and can carry diagnostic and/or therapeutic cargo agents through chemical conjugation, in vitro disassembly/reassembly process, or assembly-mediated encapsulation. Here, we developed porous SpyCatcher-mi3 (SC-mi3) as modular delivery nanoplatforms, capable of loading cargos through pores and displaying targeting ligands using SpyCatchers (SC) as anchors for SpyTagged (ST) ligands. Fluorescent dyes (F5M and A647) and a pH-sensitive prodrug (Aldox) were conjugated to the interior surface cysteines of SC-mi3, forming F5M@SC-mi3, A647@SC-mi3, and Aldox@SC-mi3. Subsequently, EGFR-binding affibody molecules (EGFRAfb) were displayed on the exterior surface of F5M@SC-mi3 and Aldox@SC-mi3 using the SC/ST protein ligation system, forming F5M@mi3/EGFRAfb and Aldox@mi3/EGFRAfb, respectively. F5M@mi3/EGFRAfb selectively bound to EGFR-overexpressing MDA-MB-468 cells, visualizing the target cancer cells, while Aldox@mi3/EGFRAfb selectively delivered doxorubicin, leading to target-specific cancer cell death. To encapsulate large proteins within SC-mi3, biotins were initially conjugated to the interior surface (BPM@SC-mi3) and mSA2-fused protein cargo molecules (mSA2-HaloTag and mSA2-yCD) were successfully introduced through the pores and securely encapsulated, forming TMR-H@SC-mi3 and yCD@SC-mi3, respectively. Subsequent display of EGFRAfb on their surface allowed the visualization of target cancer cells using fluorescent HaloTag ligand labeling and facilitated the killing of target cancer cells by converting the prodrug 5-FC to the cytotoxic drug 5-FU. Modular functionalization of the two distinct spaces in porous SC-mi3 may offer opportunities for developing target-specific functional cargo-delivery nanoplatforms in biomedical fields.

NIR-activatable nitric oxide generator based on nanoparticles loaded small-molecule photosensitizers for synergetic photodynamic/gas therapy.

BACKGROUND: Therapeutic approaches that combine conventional photodynamic therapy (PDT) with gas therapy (GT) to sensitize PDT are an attractive strategy, but the molecular structure design of the complex lacks effective guiding strategies. RESULTS: Herein, we have developed a nanoplatforms Cy-NMNO@SiO2 based on mesoporous silica materials loaded NIR-activatable small-molecule fluorescent probe Cy-NMNO for the synergistic treatment of photodynamic therapy/gas therapy (PDT/GT) in antibacterial and skin cancer. The theoretical calculation results showed that the low dissociation of N-NO in Cy-NMNO enabled it to dissociate effectively under NIR light irradiation, which is conducive to produce Cy and NO. Cy showed better 1O2 generation performance than Cy-NMNO. The cytotoxicity of Cy-NMNO obtained via the synergistic effect of GT and PDT synergistically enhances the effect of photodynamic therapy, thus achieving more effective tumor treatment and sterilization than conventional PDT. Moreover, the nanoplatforms Cy-NMNO@SiO2 realized efficient drug loading and drug delivery. CONCLUSIONS: This work not only offers a promising approach for PDT-GT synergistic drug delivery system, but also provides a valuable reference for the design of its drug molecules.

Stimulus-responsive drug delivery nanoplatforms for inflammatory bowel disease therapy.

Inflammatory bowel disease (IBD) manifests as inflammation in the colon, rectum, and ileum, presenting a global health concern with increasing prevalence. Therefore, effective anti-inflammatory therapy stands as a promising strategy for the prevention and management of IBD. However, conventional nano drug delivery systems (NDDSs) for IBD face many challenges in targeting the intestine, such as physiological and pathological barriers, genetic variants, disease severity, and nutritional status, which often result in nonspecific tissue distribution and uncontrolled drug release. To address these limitations, stimulus-responsive NDDSs have received considerable attention in recent years due to their advantages in providing controlled release and enhanced targeting. This review provides an overview of the pathophysiological mechanisms underlying IBD and summarizes recent advancements in microenvironmental stimulus-responsive nanocarriers for IBD therapy. These carriers utilize physicochemical stimuli such as pH, reactive oxygen species, enzymes, and redox substances to deliver drugs for IBD treatment. Additionally, pivotal challenges in the future development and clinical translation of stimulus-responsive NDDSs are emphasized. By offering insights into the development and optimization of stimulus-responsive drug delivery nanoplatforms, this review aims to facilitate their application in treating IBD. STATEMENT OF SIGNIFICANCE: This review highlights recent advancements in stimulus-responsive nano drug delivery systems (NDDSs) for the treatment of inflammatory bowel disease (IBD). These innovative nanoplatforms respond to specific environmental triggers, such as pH reactive oxygen species, enzymes, and redox substances, to release drugs directly at the inflammation site. By summarizing the latest research, our work underscores the potential of these technologies to improve drug targeting and efficacy, offering new directions for IBD therapy. This review is significant as it provides a comprehensive overview for researchers and clinicians, facilitating the development of more effective treatments for IBD and other chronic inflammatory diseases.

Eumelanin-Enhanced Photothermal Disinfection of Contact Lenses Using a Sustainable Marine Nanoplatform Engineered with Electrospun Nanofibers.

Bacterial keratitis (BK) is a severe eye infection commonly associated with Staphylococcus aureus (S. aureus), posing a significant risk to vision, especially among contact lens wearers. This research introduces a novel smart nanoplatform (deMS@cNF), developed from demineralized mussel shells (deMS) and reinforced with chitin (CT) nanofibrils, specifically designed for portable photothermal disinfection of contact lenses. The nanoplatform leverages the photothermal properties of eumelanin in mussel shells (MS), which, when activated by a simple bike flashlight, rapidly heats to temperatures up to 95 °C, effectively destroying bacterial contamination. In vitro tests demonstrate that the nanoplatform is biocompatible and non-toxic, making it suitable for medical applications. This study highlights an innovative approach to converting marine biowaste into a safe, effective, and low-cost portable method for disinfecting contact lenses, showcasing the potential of the deMS@cNF platform for broader antimicrobial applications.

Improving hemocompatibility in tissue-engineered products employing heparin-loaded nanoplatforms.

The enhancement of hemocompatibility through the use of nanoplatforms loaded with heparin represents a highly desirable characteristic in the context of emerging tissue engineering applications. The significance of employing heparin in biological processes is unquestionable, owing to its ability to interact with a diverse range of proteins. It plays a crucial role in numerous biological processes by engaging in interactions with diverse proteins and hydrogels. This review provides a summary of recent endeavors focused on augmenting the hemocompatibility of tissue engineering methods through the utilization of nanoplatforms loaded with heparin. This study also provides a comprehensive review of the various applications of heparin-loaded nanofibers and nanoparticles, as well as the techniques employed for encapsulating heparin within these nanoplatforms. The biological and physical effects resulting from the encapsulation of heparin in nanoplatforms are examined. The potential applications of heparin-based materials in tissue engineering are also discussed, along with future perspectives in this field.

Unlocking the Medicinal Potential of Plant-Derived Extracellular Vesicles: current Progress and Future Perspectives.

Botanical preparations for herbal medicine have received more and more attention from drug researchers, and the extraction of active ingredients and their successful clinical application have become an important direction of drug research in major pharmaceutical companies, but the complexity of extracts, multiple side effects, and significant individual differences have brought many difficulties to the clinical application of herbal preparations. It is noteworthy that extracellular vesicles as active biomolecules extracted from medicinal plants are believed to be useful for the treatment of a variety of diseases, including cancer, inflammation, regenerative-restorative and degenerative diseases, which may provide a new direction for the clinical utilization of herbal preparations. In this review, we sort out recent advances in medicinal plant extracellular vesicles and discuss their potential as disease therapeutics. Finally, future challenges and research directions for the clinical translation of medicinal plant extracellular vesicles are also discussed, and we expect that continued development based on medicinal plant extracellular vesicles will facilitate the clinical application of herbal preparations.

Challenges in Optimizing Nanoplatforms Used for Local and Systemic Delivery in the Oral Cavity.

In this study, we focused on innovative approaches to improve drug administration in oral pathology, especially by transmucosal and transdermal pathways. These improvements refer to the type of microneedles used (proposing needles in the saw), to the use of certain enhancers such as essential oils (which, besides the amplifier action, also have intrinsic actions on oral health), to associations of active substances with synergistic action, as well as the use of copolymeric membranes, cemented directly on the tooth. We also propose a review of the principles of release at the level of the oral mucosa and of the main release systems used in oral pathology. Controlled failure systems applicable in oral pathology include the following: fast dissolving films, mucoadhesive tablets, hydrogels, intraoral mucoadhesive films, composite wafers, and smart drugs. The novelty elements brought by this paper refer to the possibilities of optimizing the localized drug delivery system in osteoarthritis of the temporomandibular joint, neuropathic pain, oral cancer, periodontitis, and pericoronitis, as well as in maintaining oral health. We would like to mention the possibility of incorporating natural products into the controlled failure systems used in oral pathology, paying special attention to essential oils.

Boosting antitumor efficacy using docetaxel-loaded nanoplatforms: from cancer therapy to regenerative medicine approaches.

The intersection of nanotechnology and pharmacology has revolutionized the delivery and efficacy of chemotherapeutic agents, notably docetaxel, a key drug in cancer treatment. Traditionally limited by poor solubility and significant side effects, docetaxel's therapeutic potential has been significantly enhanced through its incorporation into nanoplatforms, such as nanofibers and nanoparticles. This advancement offers targeted delivery, controlled release, and improved bioavailability, dramatically reducing systemic toxicity and enhancing patient outcomes. Nanofibers provide a versatile scaffold for the controlled release of docetaxel, utilizing techniques like electrospinning to tailor drug release profiles. Nanoparticles, on the other hand, enable precise drug delivery to tumor cells, minimizing damage to healthy tissues through sophisticated encapsulation methods such as nanoprecipitation and emulsion. These nanotechnologies not only improve the pharmacokinetic properties of docetaxel but also open new avenues in regenerative medicine by facilitating targeted therapy and cellular regeneration. This narrative review highlights the transformative impact of docetaxel-loaded nanoplatforms in oncology and beyond, showcasing the potential of nanotechnology to overcome the limitations of traditional chemotherapy and pave the way for future innovations in drug delivery and regenerative therapies. Through these advancements, nanotechnology promises a new era of precision medicine, enhancing the efficacy of cancer treatments while minimizing adverse effects.

Glycosylated nanoplatforms: From glycosylation strategies to implications and opportunities for cancer theranostics.

Glycosylated nanoplatforms have emerged as promising tools in the field of cancer theranostics, integrating both therapeutic and diagnostic functionalities. These nanoscale platforms are composed of different materials such as lipids, polymers, carbons, and metals that can be modified with glycosyl moieties to enhance their targeting capabilities towards cancer cells. This review provides an overview of different modification strategies employed to introduce glycosylation onto nanoplatforms, including chemical conjugation, enzymatic methods, and bio-orthogonal reactions. Furthermore, the potential applications of glycosylated nanoplatforms in cancer theranostics are discussed, focusing on their roles in drug delivery, imaging, and combination therapy. The ability of these nanoplatforms to selectively target cancer cells through specific interactions with overexpressed glycan receptors is highlighted, emphasizing their potential for enhancing efficacy and reducing the side effects compared to conventional therapies. In addition, the incorporation of diagnostic components onto the glycosylated nanoplatforms provided the capability of simultaneous imaging and therapy and facilitated the real-time monitoring of treatment response. Finally, challenges and future perspectives in the development and translation of glycosylated nanoplatforms for clinical applications are addressed, including scalability, biocompatibility, and regulatory considerations. Overall, this review underscores the significant progress made in the field of glycosylated nanoplatforms and their potential to revolutionize cancer theranostics.

Engineering Nanoplatforms for Theranostics of Atherosclerotic Plaques.

Atherosclerotic plaque formation is considered the primary pathological mechanism underlying atherosclerotic cardiovascular diseases, leading to severe cardiovascular events such as stroke, acute coronary syndromes, and even sudden cardiac death. Early detection and timely intervention of plaques are challenging due to the lack of typical symptoms in the initial stages. Therefore, precise early detection and intervention play a crucial role in risk stratification of atherosclerotic plaques and achieving favorable post-interventional outcomes. The continuously advancing nanoplatforms have demonstrated numerous advantages including high signal-to-noise ratio, enhanced bioavailability, and specific targeting capabilities for imaging agents and therapeutic drugs, enabling effective visualization and management of atherosclerotic plaques. Motivated by these superior properties, various noninvasive imaging modalities for early recognition of plaques in the preliminary stage of atherosclerosis are comprehensively summarized. Additionally, several therapeutic strategies are proposed to enhance the efficacy of treating atherosclerotic plaques. Finally, existing challenges and promising prospects for accelerating clinical translation of nanoplatform-based molecular imaging and therapy for atherosclerotic plaques are discussed. In conclusion, this review provides an insightful perspective on the diagnosis and therapy of atherosclerotic plaques.

Promoting osteogenesis and bone regeneration employing icariin-loaded nanoplatforms.

There is an increasing demand for innovative strategies that effectively promote osteogenesis and enhance bone regeneration. The critical process of bone regeneration involves the transformation of mesenchymal stromal cells into osteoblasts and the subsequent mineralization of the extracellular matrix, making up the complex mechanism of osteogenesis. Icariin's diverse pharmacological properties, such as anti-inflammatory, anti-oxidant, and osteogenic effects, have attracted considerable attention in biomedical research. Icariin, known for its ability to stimulate bone formation, has been found to encourage the transformation of mesenchymal stromal cells into osteoblasts and improve the subsequent process of mineralization. Several studies have demonstrated the osteogenic effects of icariin, which can be attributed to its hormone-like function. It has been found to induce the expression of BMP-2 and BMP-4 mRNAs in osteoblasts and significantly upregulate Osx at low doses. Additionally, icariin promotes bone formation by stimulating the expression of pre-osteoblastic genes like Osx, RUNX2, and collagen type I. However, icariin needs to be effectively delivered to bone to perform such promising functions.Encapsulating icariin within nanoplatforms holds significant promise for promoting osteogenesis and bone regeneration through a range of intricate biological effects. When encapsulated in nanofibers or nanoparticles, icariin exerts its effects directly at the cellular level. Recalling that inflammation is a critical factor influencing bone regeneration, icariin's anti-inflammatory effects can be harnessed and amplified when encapsulated in nanoplatforms. Also, while cell adhesion and cell migration are pivotal stages of tissue regeneration, icariin-loaded nanoplatforms contribute to these processes by providing a supportive matrix for cellular attachment and movement. This review comprehensively discusses icariin-loaded nanoplatforms used for bone regeneration and osteogenesis, further presenting where the field needs to go before icariin can be used clinically.

The Application of Nanotechnological Therapeutic Platforms against Gynecological Cancers.

Gynecological cancers (GCs), ovarian, cervical, and endometrial/uterine cancers, are often associated with poor outcomes. Despite the development of several therapeutic modalities against GCs, the effectiveness of the current therapeutic approaches is limited due to their side effects, low therapeutic index, short halflife, and resistance to therapy. To overcome these limitations, nano delivery-based approaches have been introduced with the potential of targeted delivery, reduced toxicity, controlled release, and improved bioavailability of various cargos. This review summarizes the application of different nanoplatforms, such as lipid-based, metal- based, and polymeric nanoparticles, to improve the chemo/radio treatments of GC. In the following work, the use of nanoformulated agents to fight GCs has been mentioned in various clinical trials. Although nanosystems have their own challenges, the knowledge highlighted in this article could provide deep insight into translations of NPs approaches to overcome GCs.

Biosustainable Hybrid Nanoplatforms as Photoacoustic Agents.

The development of biosafe theranostic nanoplatforms has attracted great attention due to their multifunctional behavior, reduced potential toxicity, and improved long-term safety. When considering photoacoustic contrast agents and photothermal conversion tools, melanin and constructs like melanin are highly appealing due to their ability to absorb optical energy and convert it into heat. Following a sustainable approach, in this study, silver-melanin like-silica nanoplatforms are synthesized exploiting different bio-available and inexpensive phenolic acids as potential melanogenic precursors and exploring their role in tuning the final systems architecture. The UV-Vis combined with X-Ray Diffraction investigation proves metallic silver formation, while Transmission Electron Microscopy analysis reveals that different morphologies can be obtained by properly selecting the phenolic precursors. By looking at the characterization results, a tentative formation mechanism is proposed to explain how phenolic precursors' redox behavior may affect the nanoplatforms' structure. The antibacterial activity experiments showed that all synthesized systems have a strong inhibitory effect on Escherichia coli, even at low concentrations. Furthermore, very sensitive Photoacoustic Imaging capabilities and significant photothermal behavior under laser irradiation are exhibited. Finally, a marked influence of phenol nature on the final system architecture is revealed resulting in a significant effect on both biological and photoacoustic features of the obtained systems. These melanin-based hybrid systems exhibit excellent potential as triggerable nanoplatforms for various biomedical applications.

Nanoplatform-Based In Vivo Gene Delivery Systems for Cancer Therapy.

Gene therapy uses modern molecular biology methods to repair disease-causing genes. As a burgeoning therapeutic, it has been widely applied for cancer therapy. Since 1989, there have been numerous clinical gene therapy cases worldwide. However, a few are successful. The main challenge of clinical gene therapy is the lack of efficient and safe vectors. Although viral vectors show high transfection efficiency, their application is still limited by immune rejection and packaging capacity. Therefore, the development of non-viral vectors is overwhelming. Nanoplatform-based non-viral vectors become a hotspot in gene therapy. The reasons are mainly as follows. 1) Non-viral vectors can be engineered to be uptaken by specific types of cells or tissues, providing effective targeting capability. 2) Non-viral vectors can protect goods that need to be delivered from degradation. 3) Nanoparticles can transport large-sized cargo such as CRISPR/Cas9 plasmids and nucleoprotein complexes. 4) Nanoparticles are highly biosafe, and they are not mutagenic in themselves compared to viral vectors. 5) Nanoparticles are easy to scale preparation, which is conducive to clinical conversion and application. Here, an overview of the categories of nanoplatform-based non-viral gene vectors, the limitations on their development, and their applications in cancer therapy.

Functional 2D Nanoplatforms Alleviate Eosinophilic Chronic Rhinosinusitis by Modulating Eosinophil Extracellular Trap Formation.

The therapeutic outcomes of patients with eosinophilic chronic rhinosinusitis (ECRS) remain unsatisfactory, largely because the underlying mechanisms of eosinophilic inflammation are uncertain. Here, it is shown that the nasal secretions of ECRS patients have high eosinophil extracellular trap (EET) and cell-free DNA (cfDNA) levels. Moreover, the cfDNA induced EET formation by activating toll-like receptor 9 (TLR9) signaling. After demonstrating that DNase I reduced eosinophilic inflammation by modulating EET formation, linear polyglycerol-amine (LPGA)-coated TiS2 nanosheets (TLPGA) as functional 2D nanoplatforms with low cytotoxicity, mild protein adsorption, and increased degradation rate is developed. Due to the more flexible linear architecture, TLPGA exhibited higher cfDNA affinity than the TiS2 nanosheets coated with dendritic polyglycerol-amine (TDPGA). TLPGA reduced cfDNA levels in the nasal secretions of ECRS patients while suppressing cfDNA-induced TLR9 activation and EET formation in vitro. TLPGA displayed exceptional biocompatibility, preferential nasal localization, and potent inflammation modulation in mice with eosinophilic inflammation. These results highlight the pivotal feature of the linear molecular architecture and 2D sheet-like nanostructure in the development of anti-inflammation nanoplatforms, which can be exploited for ECRS treatment.

Hydrogen sulfide responsive nanoplatforms: Novel gas responsive drug delivery carriers for biomedical applications.

Hydrogen sulfide (H2S) is a toxic, essential gas used in various biological and physical processes and has been the subject of many targeted studies on its role as a new gas transmitter. These studies have mainly focused on the production and pharmacological side effects caused by H2S. Therefore, effective strategies to remove H2S has become a key research topic. Furthermore, the development of novel nanoplatforms has provided new tools for the targeted removal of H2S. This paper was performed to review the association between H2S and disease, related H2S inhibitory drugs, as well as H2S responsive nanoplatforms (HRNs). This review first analyzed the role of H2S in multiple tissues and conditions. Second, common drugs used to eliminate H2S, as well as their potential for combination with anticancer agents, were summarized. Not only the existing studies on HRNs, but also the inhibition H2S combined with different therapeutic methods were both sorted out in this review. Furthermore, this review provided in-depth analysis of the potential of HRNs about treatment or detection in detail. Finally, potential challenges of HRNs were proposed. This study demonstrates the excellent potential of HRNs for biomedical applications.

Empowering Cartilage Restructuring with Biodegradable Magnesium Doped-Silicon Based-Nanoplatforms: Sustained Delivery and Enhanced Differentiation Potential.

Background: Cartilage-related diseases, such as hypoplastic chondrodysplasia a rare genetic disorder that affects newborns, causing abnormal cartilage development and restricted skeletal growth. However, the development of effective treatment strategies for chondrodysplasia still faces significant challenges due to limitations in the controlled drug delivery, biocompatibility, and biodegradability of nanomedicines. Methods: A biodegradable magnesium doped-silicon based-nanoplatforms based on silicon nanoparticles (MON) was constructed. Briefly, the MON was modified with sulfhydryl groups using MPTMS to form MOS. Further engineering of MOS was achieved by incorporating Mg2+ ions through the "dissolution-regrowth" method, resulting in MMOS. Ica was effectively loaded into the MMOS channels, and HA was anchored on the surface of MOS to obtain MMOS-Ica@HA nanoplatforms. Additionally, in vitro cell experiments and in vivo zebrafish embryo models were used to evaluate the effect of the nanoplatforms on cartilage differentiation or formation and the efficiency of treating chondrodysplasia. Results: A series of characterization tests including TEM, SEM, DLS, XPS, EDX, and BET analysis validate the successful preparation of MOS-Ica@HA nanoplatforms. The prepared nanoplatforms show excellent dispersion and controllable drug release behavior. The cytotoxicity evaluation reveals the good biocompatibility of MOS-Ica@HA due to the sustained and controllable release of Ica. Importantly, the presence of Ica and Mg component in MOS-Ica@HA significantly promote chondrogenic differentiation of BMSCs via the Smad5/HIF-1α signaling pathway. In vitro and in vivo experiments confirmed that the nanoplatforms improved chondrodysplasia by promoting cartilage differentiation and formation. Conclusion: The findings suggest the potential application of the developed biodegradable MMOS-Ica@HA nanoplatforms with acceptable drug loading capacity and controlled drug release in chondrodysplasia treatment, which indicates a promising approach for the treatment of chondrodysplasia.

Advances in Nanoplatforms for Immunotherapy Applications Targeting the Tumor Microenvironment.

Cancer immunotherapy is a treatment method that activates or enhances the autoimmune response of the body to fight tumor growth and metastasis, has fewer toxic side effects and a longer-lasting efficacy than radiotherapy and chemotherapy, and has become an important means for the clinical treatment of cancer. However, clinical results from immunotherapy have shown that most patients lack responsiveness to immunotherapy and cannot benefit from this treatment strategy. The tumor microenvironment (TME) plays a critical role in the response to immunotherapy. The TME typically prevents effective lymphocyte activation, reducing their infiltration, and inhibiting the infiltration of effector T cells. According to the characteristic differences between the TME and normal tissues, various nanoplatforms with TME targeting and regulation properties have been developed for more precise regulation of the TME and have the ability to codeliver a variety of active pharmaceutical ingredients, thereby reducing systemic toxicity and improving the therapeutic effect of antitumor. In addition, the precise structural design of the nanoplatform can integrate specific functional motifs, such as surface-targeted ligands, degradable backbones, and TME stimulus-responsive components, into nanomedicines, thereby reshaping the tumor microenvironment, improving the body's immunosuppressive state, and enhancing the permeability of drugs in tumor tissues, in order to achieve controlled and stimulus-triggered release of load cargo. In this review, the physiological characteristics of the TME and the latest research regarding the application of TME-regulated nanoplatforms in improving antitumor immunotherapy will be described. Furthermore, the existing problems and further applications perspectives of TME-regulated platforms for cancer immunotherapy will also be discussed.