Supramolecular nanoparticles based on elastin-like peptides modified capsid protein as drug delivery platform with enhanced cancer chemotherapy efficacy.

Cancer, a prevalent disease posing significant threats to human health and longevity, necessitates effective therapeutic interventions. Chemotherapy has emerged as a primary strategy following surgical procedures for combating most malignancies. Despite the considerable efficacy of conventional chemotherapeutic agents against cancer cells, their utility is hindered by profound challenges such as multidrug resistance and deleterious toxic side effects, thereby limiting their systemic application. To tackle these challenges, we have devised a promising nanomedicine platform based on a plant virus. Specifically, we have selected the cowpea melanoma mottled virus (CCMV) as our nano-delivery system owing to its monodisperse and homogeneous size, as well as its intrinsic ability for controlled self-assembly. Leveraging the potential of this platform, we have engineered CCMV-based nanoparticles functionalized with elastin-like peptides (ELPs) at their N-terminal region. The target protein, CP-ELP, was expressed via E.coli, enabling encapsulation of the model drug DOX upon structural domain modification of the protein. The resulting nanoparticles exhibit uniform size distribution, facilitating efficient internalization by tumor cells and subsequent intracellular drug release, leading to enhanced antitumor efficacy. In addition, EVLP@DOX nanoparticles were found to activate immune response of tumor microenvironment in vivo, which further inhibiting tumor growth. Our designed nanoparticles have also demonstrated remarkable therapeutic effectiveness and favorable biological safety profiles in both murine melanoma and colorectal cancer models.

Self-Adhesive, Strong Antifouling, and Mechanically Reinforced Methacrylate Hyaluronic Acid Cross-Linked Carboxybetaine Zwitterionic Hydrogels.

Hyaluronic acid and zwitterionic hydrogels are soft materials with poor mechanical properties. The unique structures and physiological properties make them attractive candidates for ideal hydrogel dressings, but the crux of lacking satisfying mechanical strengths and adhesive properties is still pendent. In this study, the physical cross-linking of dipole-dipole interactions of zwitterionic pairs was utilized to enhance the mechanical properties of hydrogels. The hydrogels have been prepared by copolymerizing methacrylate hyaluronic (HAGMA) with carboxybetaine methacrylamide (CBMAA) (the mass ratio of [HAGMA]/[CBMAA] is 2:5, 1:5, 1:10, or 1:20), obtaining HA-CB2.5, HA-CB5.0, HA-CB10.0, or HA-CB20.0 hydrogel. Therein, the HA-CB20.0 hydrogel with a high CBMAA content can generate a strong dipole-dipole interaction to form internal physical cross-links, exhibit stretchability and low elastic modulus, and withstand 99% compressive deformation and cyclic compression under strain at 90%. Moreover, the HA-CB20.0 hydrogel is adhesive to diverse substrates, including skin, glass, stainless steel, and plastic. The synergistic effect of HAGMA and CBMAA shows strong anti-biofouling, high water absorption, biodegradability under hyaluronidase, and biocompatibility.

Functionalized Virus Nanoparticles Alleviates Osteoporosis via Targeting the Function of RANK-Specific Motifs.

Osteoporosis is a common skeletal disease characterized by excessive osteoclast-induced bone loss. RANKL/RANK signaling pathway is essential for osteoclastogenesis and is a key target for osteoporosis. However, regarding the fact that RANKL/RANK also functions beyond bone, the total block of RANKL/RANK will have unwanted impact on other organs. Our previous study revealed that mutation of RANK-specific motifs inhibited osteoclastogenesis without effects on other organs in mice. However, the instability and low cellular uptake efficiency limited the application of the therapeutic peptide originating from the amino acid sequence of RANK-specific motifs (RM). To this end, in this study, the peptide RM (SRPVQEQGGA (C to N terminal)) was chemically modified onto the surface of the plant virus-based nanoparticles cowpea chlorotic mottle virus (CCMV). Subsequent experiments showed that the novel virus nanoparticles RM-CCMV had excellent biocompatibility and stability, which ultimately facilitated its cellular uptake efficiency and improved its inhibitive effects on osteoclastogenesis. Moreover, RM-CCMV achieved bone enrichment and suppressed bone resorption by inhibiting osteoclastogenesis and improving the parameters of bone histomorphology in murine femurs. To be mentioned, the effective dose of CCMV conjugated RM was only 6.25% of free RM. In summary, these results have provided a promising therapeutic strategy for osteoporosis.

Self-Adaptive Antibacterial Scaffold with Programmed Delivery of Osteogenic Peptide and Lysozyme for Infected Bone Defect Treatment.

Bone defects caused by disease or trauma are often accompanied by infection, which severely disrupts the normal function of bone tissue at the defect site. Biomaterials that can simultaneously reduce inflammation and promote osteogenesis are effective tools for addressing this problem. In this study, we set up a programmed delivery platform based on a chitosan scaffold to enhance its osteogenic activity and prevent implant-related infections. In brief, the osteogenic peptide sequence (YGFGG) was modified onto the surface of cowpea chlorotic mottle virus (CCMV) to form CCMV-YGFGG nanoparticles. CCMV-YGFGG exhibited good biocompatibility and osteogenic ability in vitro. Then, CCMV-YGFGG and lysozyme were loaded on the chitosan scaffold, which exhibited a good antibacterial effect and promoted bone regeneration for infected bone defect treatment. As a delivery platform, the scaffold showed staged release of lysozyme and CCMV-YGFGG, which facilitates the regeneration of infected bone defects. Our study provides a novel and promising strategy for the treatment of infected bone defects.

Tumor Microenvironment-Adaptive Nanoplatform Synergistically Enhances Cascaded Chemodynamic Therapy.

Chemodynamic therapy (CDT), a noninvasive strategy, has emerged as a promising alternative to conventional chemotherapy for treating tumors. However, its therapeutic effect is limited by the amount of H2O2, pH value, the hypoxic environment of tumors, and it has suboptimal tumor-targeting ability. In this study, tumor cell membrane-camouflaged mesoporous Fe3O4 nanoparticles loaded with perfluoropentane (PFP) and glucose oxidase (GOx) are used as a tumor microenvironment-adaptive nanoplatform (M-mFeP@O2-G), which synergistically enhances the antitumor effect of CDT. Mesoporous Fe3O4 nanoparticles are selected as inducers for photothermal and Fenton reactions and as nanocarriers. GOx depletes glucose within tumor cells for starving the cells, while producing H2O2 for subsequent ·OH generation. Moreover, PFP, which can carry O2, relieves hypoxia in tumor cells and provides O2 for the cascade reaction. Finally, the nanoparticles are camouflaged with osteosarcoma cell membranes, endowing the nanoparticles with homologous targeting and immune escape abilities. Both in vivo and in vitro evaluations reveal high synergistic therapeutic efficacy of M-mFeP@O2-G, with a desirable tumor-inhibition rate (90.50%), which indicates the great potential of this platform for clinical treating cancer.

Microbiome in cancer: An exploration of carcinogenesis, immune responses and immunotherapy.

Cancer is a major disease endangering human health. More and more studies have shown that microorganisms play an extremely important role in the occurrence, development and treatment of tumors. As a very promising tumor treatment strategy, immunotherapy has also been proved to have a great relationship with microorganisms. Here, the authors review the contribution of the microbiota to cancer and the research on its impact on cancer immunotherapy. We also highlight the possible mechanism of their interaction and outlined the potential application of microbiota in tumor immunotherapy.

Osteogenic growth peptide (OGP)-loaded amphiphilic peptide (NapFFY) supramolecular hydrogel promotes osteogenesis and bone tissue reconstruction.

Efficient bone reconstruction after bone injury remains a great challenge. Injectable supramolecular hydrogels based on amphiphilic peptide have been widely used due to their good biocompatability, non-immunogenicity, and manipulable physicochemical properties by sequence design. Herein, we used a well-studied hydrogelator, NapFFY, to coassemble with osteogenic growth peptide (OGP) to prepare a supramolecular hydrogel, NapFFY-OGP. Both in vitro and in vivo studies demonstrate that OGP was ideally synchronously, and continuously released from the hydrogel to effectively promote the regeneration and reconstruction of skull bone defects. More specifically, after the embedding the rat skull defect area with NapFFY-OGP hydrogels, a bone regeneration rate of 37.54% bone volume fraction (BV/TV) was achieved compared to that of NapFFY hydrogel group (25.09%). NapFFY-OGP hydrogel shows great promise in the clinic repair of bone defects in the future.