Immunomodulatory Prodrug Micelles Imitate Mild Heat Effects to Reshape Tumor Microenvironment for Enhanced Cancer Immunotherapy.

Physical stimulation with mild heat possesses the notable ability to induce immunomodulation within the tumor microenvironment (TME). It transforms the immunosuppressive TME into an immune-active state, making tumors more receptive to immune checkpoint inhibitor (ICI) therapy. Transient receptor potential vanilloid 1 (TRPV1), which can be activated by mild heat, holds the potential to induce these alterations in the TME. However, achieving precise temperature control within tumors while protecting neighboring tissues remains a significant challenge when using external heat sources. Taking inspiration from the heat sensation elicited by capsaicin-containing products activating TRPV1, this study employs capsaicin to chemically stimulate TRPV1, imitating immunomodulatory benefits akin to those induced by mild heat. This involves developing a glutathione (GSH)-responsive immunomodulatory prodrug micelle system to deliver capsaicin and an ICI (BMS202) concurrently. Following intravenous administration, the prodrug micelles accumulate at the tumor site through the enhanced permeability and retention effect. Within the GSH-rich TME, the micelles disintegrate and release capsaicin and BMS202. The released capsaicin activates TRPV1 expressed in the TME, enhancing programmed death ligand 1 expression on tumor cell surfaces and promoting T cell recruitment into the TME, rendering it more immunologically active. Meanwhile, the liberated BMS202 blocks immune checkpoints on tumor cells and T cells, activating the recruited T cells and ultimately eradicating the tumors. This innovative strategy represents a comprehensive approach to fine-tune the TME, significantly amplifying the effectiveness of cancer immunotherapy by exploiting the TRPV1 pathway and enabling in situ control of immunomodulation within the TME.

Modified Coprecipitation Synthesis of Nickel-Rich NMC (Li1.0Ni0.6Mn0.2Co0.2O2) for Lithium-Ion Batteries: A Simple, Cost-Effective, Environmentally Friendly Method.

Lithium-ion batteries lay the foundation for satisfying the fast-growing demand of portable electronics and electric vehicles. However, due to the complexity of material syntheses, high fabrication temperature condition, and toxic gas emission, high volume manufacturing of lithium-ion batteries is still challenging. Here, we propose a modified coprecipitation method to synthesize Li1.0Ni0.6Mn0.2Co0.2O2 (NMC622-MCP) as a cathode material in a simple, cost-effective, and environmentally friendly approach. We demonstrate that the proposed method can be operated in a lower temperature environment, with respect to the requirement of conventional synthesis methods. Furthermore, only CO2 gas is emitted during synthesis. We also employed first-principles simulations to evaluate the crystallinity of the synthesized materials via X-ray diffractometer patterns. During charge/discharge processes, the obtained cathode materials induce outstanding electrochemical performance with a maximum specific capacity of up to 206.9 mAh g-1 at 0.05 C and a retention capacity of 83.22% after 100 cycles. Thus, the simple, cost-effective, environmentally friendly, and highly electrochemical performance of the newly acquired material envisages the modified coprecipitation method as a promising tool to manufacture cathode materials for lithium-ion batteries.

Enhanced Raman scattering based on a ZnO/Ag nanostructured substrate: an in-depth study of the SERS mechanism.

Combining semiconductor and noble metal nanostructures into a hybrid system has shown many complementary advantages in the optical properties, making them more attractive in practical applications. Herein, we prepared a semiconductor/noble metal hybrid system composed of Ag nanoparticles decorated on ZnO nanoplates acting as a surface-enhanced Raman scattering (SERS) substrate for probing methyl red. The tuning of the optical characteristics of the hybrid system was demonstrated through the changes in the absorption, fluorescence, and Raman spectra. The formation of the local electromagnetic field at the heterostructure interface plays a pivotal role in its SERS activity. Thanks to density functional theory calculations, methyl red's vibrational modes and symmetry properties were assigned to be consistent with the contribution of the neutral trans conformer and protonated state. Then, using Herzberg-Teller-surface selection rules, these assignments strongly support the realization that the SERS mechanism based on the ZnO/Ag substrate has a significant electromagnetic contribution versus the Ag substrate in which charge transfer plays a pivotal role. To the best of our knowledge, this is the first investigation that has clarified the mechanism and advantage of semiconductor/metal (ZnO/Ag nanostructures) even over noble metals (Ag nanoparticles) in SERS applications. Moreover, the SERS behavior based on the ZnO/Ag substrate was also examined and the results indicated high sensitivity and good repeatability.