Efficient Colon Cancer Immunogene Therapy by Hydrogel Ball Loaded With Two Types of Cell Membrane-Coated...

Biomimetic technology has high potential for enhancing cancer immunogene therapy. Cell membrane-coated nanoparticles (CMNPs) obtain extra targeting, recognition, and signaling transduction functions. However, a single kind of CMNPs is limited when facing complicated tumor immunogene therapy. Here reported the collaboration of two types of CMNPs using a double-layered spherical scaffold. This scaffold was prepared by stacking photosensitive hydrogels with two concentrations. After implantation, the two layers degraded successively within 5-8 days, enabling sequential and controlled release of payloads. Based on this, a MG-709 double-layered formulation which co-delivered cancer cell membrane-coated nanoparticle/siRNA complex (siStat3@CMP) in the outer layer, and DC membrane-coated nanoparticle/cancer cell lysate complex (DMLD) in the inner layer. The results demonstrated that siStat3@CMP was released first and exerted its apoptosis-inducing effect, resulting in the release of tumor-associated antigens (TAAs). Subsequently, TAAs as well as immune cells migrated into the inner layer, where they worked together with DMLD to ignite immune responses. The activated immune cells were then released to perform immunotherapeutic effects. Facilitated by this mechanism, in situ implantation of the MG-709 scaffold efficiently suppressed the development of multiple colorectal cancer models. The study provides a new solution for the collaboration of CMNPs in tumor immunogene therapy.