Injectable Liquid Crystal Formation System for Reshaping Tumor Immunosuppressive Microenvironment to Boost Antitumor Immunity: Postoperative Chemoimmunotherapy. Issue 50 (18th November 2020)

• Record Type: Journal Article
• Authors: Hu, Mei; Zhang, Jiao; Yu, Yulin; Tu, Kun; Yang, Ting; Wang, Yi; Hu, Qian; Kong, Li; Zhang, Zhiping
• Is Part Of: Small. Volume 16:Issue 50(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-11-18
• Subjects: cancer chemoimmunotherapy -- in situ vaccine -- liquid crystal formation system -- postoperative treatment -- tumor microenvironment; Nanotechnology -- Periodicals; Nanoparticles -- Periodicals; Microtechnology -- Periodicals; 620.5
• DOI: 10.1002/smll.202004905
• Languages: English
• ISSNs: 1613-6810

Abstract

Abstract: Exploring optimal strategies to improve patient outcome postoperatively is still under challenge. Cancer immunotherapy has great potential to prevent the postoperative tumor recurrence and metastasis, which could be further strengthened by re‐education of tumor microenvironment (TME). Herein, a local and sustained drug delivery system of liquid crystal formation system (LCFS) co‐loaded with doxorubicin (DOX) and resiquimod (R848) (D/R@LCFS) is reported to confer effective chemoimmunotherapy with reduced systematic toxicity. After local administration, D/R@LCFS turns tumor into in situ vaccine via DOX‐triggered immunogenic cell death effect accompanied with immunostimulatory effect of R848. Meanwhile, combination treatment of D/R@LCFS facilitates the recruitment of effector CD8 + T cells and the polarization of myeloid‐derived suppressor cells and immunosuppressive type 2‐polarized macrophages to tumoricidal antigen‐presenting cells, favoring antigen‐specific T cell immune response and inducing more immunogenic phenotypes in tumors. The generated in situ vaccine as well as reshaped TME by D/R@LCFS elicited systematic immune response and long term immune‐memory effect in combination with immune checkpoint blockade to significantly prevent postoperative B16F10 or 4T1 tumor recurrence and metastasis. Therefore, this combination strategy of spatiotemporal TME modulation is expected to provide a clinical available option for effective postoperative chemoimmunotherapy. Abstract : This work demonstrates an injectable liquid crystal formation system (LCFS) co‐loaded with DOX and R848 (D/R@LCFS) for spatiotemporal modulation of tumor microenvironment (TME). Doxorubicin in gel could induce immunogenic cell death effect, while R848 could re‐educate immunosuppressive TME with boosted systematic antitumor immune response. When aPD‐1 is combined, postoperative tumor recurrence and metastasis could be effectively prevented.