A tactical nanomissile mobilizing antitumor immunity enables neoadjuvant chemo-immunotherapy to minimize postsurgical tumor metastasis and recurrence

Neoadjuvant chemotherapy has become an indispensable weapon against high-risk resectable cancers, which benefits from tumor downstaging. However, the utility of chemotherapeutics alone as a neoadjuvant agent is incapable of generating durable therapeutic benefits to prevent postsurgical tumor metastasis and recurrence. Herein, a tactical nanomissile (TALE), equipped with a guidance system (PD-L1 monoclonal antibody), ammunition (mitoxantrone, Mit), and projectile bodies (tertiary amines modified azobenzene derivatives), is designed as a neoadjuvant chemo-immunotherapy setting, which aims at targeting tumor cells, and fast-releasing Mit owing to the intracellular azoreductase, thereby inducing immunogenic tumor cells death, and forming an in situ tumor vaccine containing damage-associated molecular patterns and multiple tumor antigen epitopes to mobilize the immune system. The formed in situ tumor vaccine can recruit and activate antigen-presenting cells, and ultimately increase the infiltration of CD8+ T cells while reversing the immunosuppression microenvironment. Moreover, this approach provokes a robust systemic immune response and immunological memory, as evidenced by preventing 83.3% of mice from postsurgical metastasis or recurrence in the B16-F10 tumor mouse model. Collectively, our results highlight the potential of TALE as a neoadjuvant chemo-immunotherapy paradigm that can not only debulk tumors but generate a long-term immunosurveillance to maximize the durable benefits of neoadjuvant chemotherapy.

Synthesis and characterization of thermosensitive hydrogel based on PEG-PCL-PEG block copolymers / 生物医学工程学杂志

In this paper, a series of low-molecular-weight PEG-PCL-PEG triblock copolymers were successfully synthesized by ring-opening polymerization method, and were characterized using 1H-NMR and FTIR. The aqueous solution displayed specific thermosensitive gel-sol transition when the concentration was above corresponding critical gel concentration (CGC). The gel-sol phase diagram was recorded using test tube-inverting method, which was depended on the hydrophilic/hydrophobic balance in macromolecular structure, as well as heating history. As a result, the gel-sol transition temperature range could be altered, which might be very useful for its application as injectable drug delivery system.