Modulating Elasticity of Liposome for Enhanced Cancer Immunotherapy.

Cancer immunotherapy has emerged as a promising approach to cancer treatment in recent years. The physical and chemical properties of nanocarriers are critical factors that regulate the immune activation of antigen-presenting cells (APCs) in the tumor microenvironment (TME). Herein, we extensively investigated the behavior of liposome nanoparticles (Lipo-NPs) with different elasticities, focusing on their interaction with immune cells and their transport mechanisms from tumors to tumor-draining lymph nodes (tdLNs). Successfully preparing Lipo-NPs with distinct elastic properties, their varied behaviors were observed, concerning immune cell interaction. Soft Lipo-NPs exhibited an affinity to cell membranes, while those with medium elasticity facilitated the cargo delivery to macrophages through membrane fusion. Conversely, hard Lipo-NPs enter macrophages via classical cellular uptake pathways. Additionally, it was noted that softer Lipo-NPs displayed superior transport to tdLNs in vivo, attributed to their deformable nature with lower elasticity. As a result, the medium elastic Lipo-NPs with agonists (cGAMP), by activating the STING pathway and enhancing transport to tdLNs, promoted abundant infiltration of tumor-infiltrating lymphocytes (TILs), leading to notable antitumor effects and extended survival in a melanoma mouse model. Furthermore, this study highlighted the potential synergistic effect of medium elasticity Lipo-NPs with immune checkpoint blockade (ICB) therapy in preventing tumor immune evasion. These findings hold promise for guiding immune-targeted delivery systems in cancer immunotherapy, particularly in vaccine design for tdLNs targeting and eradicating metastasis within tdLNs.

Human extracellular matrix (ECM)-like collagen and its bioactivity.

Collagen, the most abundant structural protein in the human extracellular matrix (ECM), provides essential support for tissues and guides tissue development. Despite its widespread use in tissue engineering, there remains uncertainty regarding the optimal selection of collagen sources. Animal-derived sources pose challenges such as immunogenicity, while the recombinant system is hindered by diminished bioactivity. In this study, we hypothesized that human ECM-like collagen (hCol) could offer an alternative for tissue engineering. In this study, a facile platform was provided for generating hCol derived from mesenchymal stem cells with a hierarchical structure and biochemical properties resembling native collagen. Our results further demonstrated that hCol could facilitate basal biological behaviors of human adipose-derived stem cells, including viability, proliferation, migration and adipocyte-like phenotype. Additionally, it could promote cutaneous wound closure. Due to its high similarity to native collagen and good bioactivity, hCol holds promise as a prospective candidate for in vitro and in vivo applications in tissue engineering.

Simulation of hydraulic-mechanical-chemical coupled acid fracturing of rock with lattice bonds.

The acid fracturing is a very important stimulation technique for carbonate reservoir. The hydraulic-mechanical-chemical effect is tightly coupled in this fracture process. In this paper, the discretized virtual internal bond is extended to simulate this coupling process in which the rock matrix is considered to consist of many discrete bond cells with finite number of bonds. Each bond is taken as transport channel of acid fluid, the reaction site of chemical dissolution and the mechanical linkage. When acid fluid flows through a bond, the bond will be dissolved. As result, both the bond porosity and permeability are increased, and the mechanical properties are weakened. By this method, the hydraulic, mechanical and chemical fields are coupled together on the micro bond. The acidization, the chemical-induced mechanical weakening and the fracture propagation can be well reproduced. This method transforms the complicated 3D multi-physical coupling problem into the 1D bond problem, which significantly simplifies the simulation of multi-field coupling process. It provides a feasible approach to simulate the HMC coupled acid fracturing process.

Virus-Like Nanotherapeutic for Spatiotemporally Enhancing Antigen Presentation and Cross-Presentation toward Potential Personalized Immunotherapy.

One of the major causes of immunotherapy resistance is the loss of major histocompatibility complex class I (MHC-I) molecules in tumor cells or the downregulation of the class I antigen presentation pathway. In this study, a novel virus-like nanotherapeutic (siRNA@HCM) is developed via encapsulating nanosized siRNA nanoparticles in a hybrid membrane comprising a personalized tumor cell membrane and a universal 293T membrane expressing the mutant vesicular stomatitis virus glycoprotein (mVSV-G). Upon intravenous administration, siRNA@HCM accumulates at the tumor site and provides two potent driving forces for antitumor immunity. First, mVSV-G induces the fusion of siRNA@HCM with tumor cell membranes and directly injects siRNAs into the cytoplasm, significantly improving tumor intrinsic MHC-I antigen presentation. Moreover, mVSV-G can promote the maturation of dendritic cells, thereby achieving highly efficient antigen cross-presentation. The results demonstrate that spatiotemporally enhancing tumor intrinsic antigen presentation and cross-presentation via siRNA@HCM can achieve satisfactory antitumor efficacy and excellent biocompatibility. Immune infiltration analysis shows that siRNA@HCM treatment turns cold tumors into hot tumors. In addition, it significantly promotes the therapeutic effect of programmed death-1 inhibitor. In summary, virus-like nanotherapeutics present a promising approach to enhance the antitumor immune response, with distinct advantages for potential personalized therapy and clinical applications.

Screening and anti-glioma activity of Chiloscyllium plagiosum anti-human IL-13Rα2 single-domain antibody.

Glioblastoma is a common and fatal malignant tumour of the central nervous system, with high invasiveness. Conventional treatments for this disease, including comprehensive treatment of surgical resection combined with chemoradiotherapy, are ineffective, with low survival rate and extremely poor prognosis. Targeted therapy is promising in overcoming the difficulties in brain tumour treatment and IL-13Rα2 is a widely watched target. The development of new therapies for glioma, however, is challenged by factors, such as the unique location and immune microenvironment of gliomas. The unique advantages of single-domain antibodies (sdAbs) may provide a novel potential treatment for brain tumours. In this study, Chiloscyllium plagiosum was immunized with recombinant IL-13Rα2 protein to produce sdAb and sdAb sequences were screened by multi-omics. The targeted sdAb genes obtained were efficiently expressed in the Escherichia coli prokaryotic expression system, showing a significant binding capacity to IL-13Rα2 in vitro. The cell proliferation and migration inhibitory effects of recombinant variable domain of the new antigen receptor (VNAR) on glioma cells were detected by CCK-8 and cell scratch assays. The sdAb obtained in this study showed high in vitro activity and favourable cell proliferation inhibitory effect on glioma cells, with potential clinical application value. The present study also provides a new direction and experimental basis for the development of targeted therapies for glioma.

Constructing Spatiotemporally Controllable Biocatalytic Cascade in RBC Nanovesicles for Precise Tumor Therapy Based on Reversibly Induced Glucose Oxidase-Magnetoferritin Dimers.

Chemodynamic therapy is a promising tumor treatment strategy. However, it remains a great challenge to overcome the unavoidable off-target damage to normal tissues. In this work, it is discovered that magnetoferritin (M-HFn, biomimic peroxidase) can form nanocomplexes with glucose oxidase (GOD) in the presence of glucose, thus inhibiting the enzyme activity of GOD. Interestingly, GOD&M-HFn (G-M) nanocomplexes can dissociate under near-infrared (NIR) laser, reactivating the enzyme cascade. Based on this new finding, a spatiotemporally controllable biocatalytic cascade in red blood cell (RBC) nanovesicles (G-M@RBC-A) is fabricated for precise tumor therapy, which in situ inhibits enzyme cascade between GOD and M-HFn during blood circulation and reactivates the cascade activity in tumor site by NIR laser irradiation. In RBC nanovesicles, GOD is grabbed by M-HFn to form G-M nanocomplexes in the presence of glucose, thus inhibiting the Fenton reaction and reducing side effects. However, after NIR laser irradiation, G-M nanocomplexes are spatiotemporally dissociated and the cascade activity is reactivated in the tumor site, initiating reactive oxygen species damage to cancer cells in vivo. Therefore, this work provides new insight into the fabrication of spatiotemporally controllable biocatalytic cascade for precise cancer therapy in the future.

Controlling the Internal Structures of Polymeric Microspheres via the Introduction of a Water-Soluble Organic Solvent.

Polymeric microspheres with different internal structures have been widely used because of their characteristics in the structures. This paper reports a method of controlling the internal structures of polymeric microspheres via the introduction of a water-soluble organic solvent to the continuous phase in the foam phase preparation of porous polymeric microspheres. The introduction of a water-soluble organic solvent enables the control of polymeric microspheres' internal structures, from porous to hollow. Because a water-soluble organic solvent is introduced, the organic solvent may be diffused toward the interface because of the affinity between the organic solvent and the oil droplets, resulting an accumulation of organic solvent molecules at the interface to form an organic solvent layer. The presence of this layer may decrease the evaporation rate of the internal organic solvent in an oil droplet, which extends the time for the mingling of porogen droplets to form a few large pores or even an extremely large single pore inside. This method is also capable of altering the thickness of hollow microspheres' shells in a desired way, with improved efficiency, yield and the capacity for continuous use on an industrial scale.