Systemic delivery of paclitaxel by find-me nanoparticles activates anti-tumor immunity and eliminates tumors

• Published in: ACS nano 2024-01, Vol.18 (4), p.3681-3698
• Main Authors: Kwon, Soonbum, Meng, Fanfei, Tamam, Hassan, Gadalla, Hytham H., Wang, Jianping, Dong, Boyang, Hopf Jannasch, Amber S., Ratliff, Timothy L., Yeo, Yoon
• Format: Article
• Language: English
• ISSN: 1936-0851; 1936-086X
• DOI: 10.1021/acsnano.3c11445

Local delivery of immune-activating agents has shown promise in overcoming immunosuppressive tumor microenvironment (TME) and stimulating anti-tumor immune responses in tumors. However, systemic therapy is ultimately needed to treat tumors that are not readily locatable or accessible. To enable systemic delivery of immune-activating agents, we employ poly(lactic-co-glycolide) (PLGA) nanoparticles (NPs) with a track record in systemic application. The surface of PLGA NPs is decorated with adenosine triphosphate (ATP), a damage-associated molecular pattern to recruit antigen-presenting cells (APCs). The ATP-conjugated PLGA NPs (NP pD -ATP) are loaded with paclitaxel (PTX), a chemotherapeutic agent inducing immunogenic cell death to generate tumor antigens in situ . We show that the NP pD -ATP retains ATP activity in hostile TME and provides a stable “find-me” signal to recruit APCs. Therefore, the PTX-loaded NP pD -ATP helps populate anti-tumor immune cells in TME and attenuate the growth of CT26 and B16F10 tumors better than a mixture of PTX-loaded NP pD and ATP. Combined with anti-PD-1 antibody, PTX-loaded NP pD -ATP achieves complete regression of CT26 tumors followed by anti-tumor immune memory. This study demonstrates the feasibility of systemic immunotherapy using a PLGA NP formulation that delivers ICD-inducing chemotherapy and an immunostimulatory signal.