In situ forming oxygen/ROS-responsive niche-like hydrogel enabling gelation-triggered chemotherapy and inhibition of metastasis

Though the development of the diverse hypoxia-activated prodrugs(HAPs)has made great progresses in the last several decades,current cancer therapy based on HAPs still suffers many obstacles,e.g.,poor therapeutic outcome owing to hard deep reaching to hypoxic region,and the occurrence of metastasis due to hypoxia.Inspired by engineered niches,a novel functional chitosan polymer(CS-FTP)is synthesized for construction of a hydrogel-based bio-niche(CS-FTP-gel)in aiming at remodeling tumor hypoxic microenvironment.The CS-FTP polymers are crosslinked to form a niche-like hydrogel via enzyme-mediated oxygen-consumable dimerization after injected into tumor,in which a HAP(i.e.,AQ4N)could be physically encapsulated,resulting in enhanced tumor hypoxia to facilitate AQ4N-AQ4 toxic transformation for maximizing efficacy of chemotherapy.Furthermore,Pazopanib(PAZ)conjugated onto the CS backbone via ROS-sensitive linker undergoes a stimuli-responsive release behavior to promote antiangiogenesis for tumor starvation,eventually contributing to the inhibition of lung metastasis and synergistic action with AQ4N-based chemotherapy for an orthotopic 4T1 breast tumor model.This study provides a promising strategy for hypoxia-based chemotherapy and demonstrates an encouraging clinical potential for multifunctional hydrogel applicable for antitumor treatment.

A novel o-nitrobenzyl-based photocleavable antitumor prodrug with the capability of releasing 5-fluorourail

An o-nitrobenzyl-based photocleavable antitumor prodrug with a terminal carboxyl group was designed and synthesized.The photolysis properties of the prodrug were investigated by means of1H NMR,HPLC,UV,and MTT methods.The results showed that the toxicity of the anticancer drug was effectively shielded before release.However,the prodrug effectively regained the antitumor capability against cancer cells by release of 5-fluorouracil when it was exposed to ultraviolet irradiation.

Tunable light emission from carbon dots by controlling surface defects

Carbon dots(CDs)are metal-free fluorescent materials that can be used in optical and electronic devices,but few studies have focused on one-step synthesis routes for CDs with tunable color and high photoluminescence quantum yield(PLQY).Herein,CDs with tunable light emission were synthesized using a novel amide-assisted solvothermal approach.The as-prepared CDs were well dispersed and homogeneous,with average diameters of approximately 2.0–4.0 nm,depending on the dopants.Owing to the surface states with different ratios of nitrogen-and oxygen-related species,different CDs can exhibit blue,green,red,or white emission with relatively high PLQYs of 61.6%,41.3%,29.1%and 19.7%,respectively.XPS measurements,in conjunction with DFT calculations,indicate that nitrogen substitution(pyridinic/pyrrolic nitrogen)dominates the blue emission,while introducing oxygen functional groups lowered the LUMO energy level,which resulted in redder emission.In addition,the CDs are demonstrated as a bioimaging probe in both in vitro and in vivo assays,and the white light CDs have been demonstrated to be potential fluorescent materials for white-light-emitting diode(WLED).

Design strategy of optical probes for tumor hypoxia imaging

Clinical manifestations of tumors indicate that malignant phenotypes developing in the hypoxic microenvironment lead to resistance to cancer treatment, rendering chemotherapy, radiotherapy, and photodynamic therapy less sensitive and effective in patients with tumor. Visualizing the oxygen level in the tumor environment has garnered much attention due to its implications in precision tumor therapy. Following the rapid development of biomaterials in nanotechnology, various nanomaterials have been designed to visualize the oxygen levels in tumors. Here, we review recent research on detecting oxygen levels in solid tumors for tumor hypoxia imaging. To monitor the hypoxic level of tumors, two main strategies were investigated: directly detecting oxygen levels in tumors and monitoring the hypoxia-assisted reduced microenvironment. We believe that hypoxia as a tumor-specific microenvironment can be a breakthrough in the clinical treatment of tumors.