Key Words:DELIVERY; NANOFORMULATIONS; BOND

Abstract:Given the over-production of glutathione (GSH) and hydrogen peroxide (H2O2) in tumor cells, redox-responsive linkers such as disulfide bonds have been widely used to develop site-specific prodrug system, but may suffer from their poor sensitivity that results in low efficacy. Herein, we report the development of a class of redox-triggered small molecule prodrugs (RhB-S(Se)-CPT), by conjugating zwitterionic rhodamine B (RhB) and camptothecin (CPT) with thio-/seleno-ether linkers. The amphiphilic prodrug can self-assemble into stable nanoparticles in water, and zwitterionic RhB is located on the surface of RhB-S(Se)-CPT nanoparticles, tracking the distribution and kinetics of drug delivery in real time, and reducing the non-specific binding to in vivo components, thus decreasing the side effects of nanomedicines. The thio-/seleno-ether linkers enable selective and rapid release of CPT in response to a redox heterogeneous intratumoral microenvironment. Interestingly, selenoether bonds exhibit significant advantages over thioether in terms of CPT release rate, intracellular toxicity and therapeutic efficacy against large tumors (similar to 200 mm(3)) in mice. These results provide insights to the rational design of subsequent redox-responsive nanoprodrug system, which may contribute to the material selection and structural design of next-generation nanomedicines for tumor theranostics.

Volume:387

Issue:wu

Translation or Not:no