Light-Induced ROS Generation and 2-DG-Activated Endoplasmic Reticulum Stress by Antitumor Nanosystems: An Effective Combination Therapy by Regulating the Tumor Microenvironment.

A multimodal cancer therapeutic nanoplatform is reported. It demonstrates a promising approach to synergistically regulating the tumor microenvironment. The combination of intracellular reactive oxygen species (ROS) generated by irradiation of photosensitizer and endoplasmic reticulum (ER) stress induced by 2-deoxy-glucose (2-DG) has a profound effect on necrotic or apoptotic cell death. Especially, targeting metabolic pathway by 2-DG is a promising strategy to promote the effect of photodynamic therapy and chemotherapy. The nanoplatform can readily release its cargoes inside cancer cells and combines the advantages of ROS-sensitive releasing chemotherapeutic drugs, upregulating apoptosis pathways under ER stress, light-induced generation of cytotoxic ROS, achieving tumor accumulation, and in vivo fluorescence imaging capability. This work highlights the importance of considering multiple intracellular stresses as design parameters for nanoscale functional materials in cell biology, immune response, as well as medical treatments of cancer, Alzheimer's disease, etc.

Folate-Modified Photoelectric Responsive Polymer Microarray as Bionic Artificial Retina to Restore Visual Function.

A high-optical-resolution artificial retina system that accurately communicates with the optic nerve is the main challenge in the modern biological science and bionic field. Here, we developed a bionic artificial retina possessing phototransduction "cells" with measurements even smaller than that of the neural cells. Using the technique of micrometer processing, we constructed a pyramid-shape periodic microarray of a photoreceptor. Each "sensing cell" took advantage of polythiophene derivative/fullerene derivative (PCBM) as a photoelectric converter. Because folic acid played an essential role in eye growth, we particularly modified the polythiophene derivatives with folic acid tags. Therefore, the artificial retina could enlarge the contact area and even recognize the nerve cells to improve the consequence of nerve stimulation. We implanted the artificial retina into blinded rats' eyes. Electrophysiological analysis revealed its recovery of photosensitive function 3 months after surgery. Our work provides an innovative idea for fabricating a high-resolution bionic artificial retina system. It shows great potential in artificial intelligence and biomedicine.

Conductive Hydrogel for a Photothermal-Responsive Stretchable Artificial Nerve and Coalescing with a Damaged Peripheral Nerve.

Modern development of flexible electronics has made use of bioelectronic materials as artificial tissue in vivo. As hydrogels are more similar to nerve tissue, functional hydrogels have become a promising candidate for bioelectronics. Meanwhile, interfacing functional hydrogels and living tissues is at the forefront of bioelectronics. The peripheral nerve injury often leads to paralysis, chronic pain, neurologic disorders, and even disability, because it has affected the bioelectrical signal transmission between the brain and the rest of body. Here, a kind of light-stimuli-responsive and stretchable conducting polymer hydrogel (CPH) is developed to explore artificial nerve. The conductivity of CPH can be enhanced when illuminated by near-infrared light, which can promote the conduction of the bioelectrical signal. When CPH is mechanically elongated, it still has high durability of conductivity and, thus, can accommodate unexpected strain of nerve tissues in motion. Thereby, CPH can better serve as an implant of the serious peripheral nerve injury in vivo, especially in the case that the length of the missing nerve exceeds 10 mm.