New Progress in Senescent Tumor Photoimmunotherapy from ECUST Published in Nature Communications
Recently, a research team led by Professor Wei’an Zhang from the School of Materials Science and Engineering at ECUST has made important progress in the treatment of senescent tumors. The findings were published in Nature Communications under the title “Chemical anchoring of immunotherapeutic drugs within senescent tumor cells overcomes senescence-driven immunotherapy resistance.”
The study is the first to report the biological phenomenon of overexpression of drug efflux pumps in senescent tumors. To address this issue, the researchers designed a drug delivery strategy based on chemical anchoring strategy, effectively overcoming drug efflux and enabling efficient regulation of the tumor immune microenvironment.
The researchers fabricated a self-assembled immunotherapeutic drug (DN-Ghcy) with dual targeting properties for both senescence and tumors. The drug was composed of a senescence-associated β-galactosidase (SA-β-gal)-activatable bio-orthogonal receptor (Ghcy) and an engineered immunostimulatory prodrug (DN). Within senescent tumor cells, DN-Ghcy was selectively immobilized via an SA-β-gal-catalyzed bio-orthogonal nano-receptor, significantly enhancing intracellular drug retention and bypassing transporter-mediated drug efflux.
Under near-infrared irradiation, DN-Ghcy concurrently mediated degradation of PD-L1, release of an indoleamine 2,3-dioxygenase (IDO) inhibitor, and disruption of lysosomal integrity. This strategy successfully reversed immunotherapy resistance in senescent tumors and established a promising therapeutic modality to overcome senescence-driven immunotherapy resistance.
ECUST is the sole corresponding institution of the paper. Professor Wei’an Zhang and Associate Professor Jia Tian are the corresponding authors, and Wenlong Huang, a PhD student from ECUST, is the first author. The research was supported by the National Natural Science Foundation of China (Key Program and General Program) and the Science and Technology Commission of Shanghai Municipality.