Bortezomib-loaded hybrid liposome inducing pyroptosis for targeted therapy against colorectal cancer.

Colorectal cancer (CRC) is a highly invasive malignant tumor. At present, the combination of surgery with chemotherapy constitutes the predominant strategy in the treatment of CRC. The serious side effects of chemotherapy profoundly impair patients' quality of life. It is of great importance to develop novel approach to reduce side effects and increase anti-tumor efficacy in CRC treatment. Bortezomib (Btz), a reversible proteasome inhibitor, possessing both chemotherapeutic and immunotherapeutic effects by inducing cell pyroptotic. However, the application of Btz is impeded by their lack of tumor-targeting capability and lipid solubility. To address these restrictions and develop an ideal drug carrier, we performed a biohybrid approach by fusing liposomes with artificial extracellular vesicles engineered from cancer cells to generate hybrid liposomes (HV@Btz) for the targeted delivery of Btz. In contrast to liposomes, HV@Btz possessed higher cellular uptake efficiency and strong cytotoxicity against CT26 cells by inducing cell pyroptotic. Additionally, HV@Btz had superior tumor-targeting ability and prolonged circulation time. HV@Btz significantly suppressed tumor growth and triggered robust anti-tumor immune response with minimum systemic toxicity in both subcutaneous and orthotopic CRC-bearing mice. This study demonstrated that HV@Btz could serve as a scalable approach by inducing cell pyroptotic for the management of colorectal cancer.