Injectable phage-loaded silk microparticles achieve efficient tumor immunotherapy

Tumor immunotherapy has attracted considerable attention owing to its potential to activate the immune system to target and attack cancer cells. However, the clinical effectiveness of immunotherapy is often restricted by the rapid clearance of drugs and their insufficient retention at the tumor site. Here, we overcome this challenge by combining silk fibroin microparticles (SMPs), a biocompatible drug carrier, and a PD-L1 binding phage (HH phage), which displays PD-L1 binding peptides on the sidewall to block PD-1/PD-L1 immune checkpoints. This combination aims to enhance intratumor drug retention and improve tumor therapy. Briefly, we functionalized silk fibroin microparticles (SMPs) with the engineered phage to generate HH-SMPs via electrostatic adsorption. After intra-tumoral injection, HH-SMPs enable controlled and sustained release of the therapeutic phages, which contributes to effective tumor therapy. In contrast to free HH phage which is rapidly cleared, this delivery system markedly increases the local concentration of phages in the tumor and substantially prolongs their intratumoral retention time. Consequently, HH-SMPs demonstrate a notably enhanced tumor-suppressive effect against LLC tumors in vivo. In addition, HH-SMPs exhibit good biocompatibility both in cell culture and in animals. Our study suggests that the HH-SMPs delivery system provides a promising approach to improving therapeutic outcomes in cancer treatment.