Syringeable immunotherapeutic nanogel reshapes tumor microenvironment and prevents tumor metastasis and recurrence.

The low response rate of current cancer immunotherapy suggests the presence of few antigen-specific T cells and a high number of immunosuppressive factors in tumor microenvironment (TME). Here, we develop a syringeable immunomodulatory multidomain nanogel (iGel) that overcomes the limitation by reprogramming of the pro-tumoral TME to antitumoral immune niches. Local and extended release of immunomodulatory drugs from iGel deplete immunosuppressive cells, while inducing immunogenic cell death and increased immunogenicity. When iGel is applied as a local postsurgical treatment, both systemic antitumor immunity and a memory T cell response are generated, and the recurrence and metastasis of tumors to lungs and other organs are significantly inhibited. Reshaping of the TME using iGel also reverts non-responding groups to checkpoint blockade therapies into responding groups. The iGel is expected as an immunotherapeutic platform that can reshape immunosuppressive TMEs and synergize cancer immunotherapy with checkpoint therapies, with minimized systemic toxicity.

Spatiotemporal Programing for the On-Demand Release of Bupivacaine Based on an Injectable Composite Hydrogel.

We report a programed drug delivery system that can tailor the release of anesthetic bupivacaine in a spatiotemporally controlled manner. The drug delivery system was developed through the combination of a collagen-based injectable hydrogel and 2 types of poly(lactic-co-glycolic acid) (PLGA) particles. As a rapid-release platform (90% release after 24 h), bupivacaine hydrochloride was incorporated into collagen/poly(γ-glutamic acid) hydrogel, which exhibited gel formation at body temperature. PLGA microparticles (diameter 1-3 µm) containing bupivacaine base showed a very slow release of bupivacaine (95% after 240 h), whereas PLGA nanoparticles (124 ± 30 nm) containing bupivacaine base demonstrated an intermediate release rate (95% after 160 h). By changing the relative composition ratio between the 3 components in these injectable composite hydrogels, the release of bupivacaine could be easily controlled from very rapid (within 1 day) to very delayed (up to 9 days). The experimental results on the release data (cumulative release, time point release, average release rate) were coincident with the release profile generated by computer simulation. These injectable composite hydrogels with systematically tunable mixing ratios are expected to serve as a promising technology for the on-demand release of bupivacaine in pain management.