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권순범Soonbum Kwon

Purdue University

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ACS Nano, Jan 16 2024, | https://doi.org/10.1021/acsnano.3c11445 Systemic Delivery of Paclitaxel by Find-Me Nanoparticles Activates Antitumor Immunity and Eliminates Tumors

Soonbum Kwon ¹, Fanfei Meng ¹, Hassan Tamam ^1,2, Hytham H Gadalla^1,3, Jianping Wang ¹, Boyang Dong ¹, Amber S Hopf Jannasch ⁴, Timothy L Ratliff ^5,6, Yoon Yeo ^1,5,7

¹Department of Industrial and Molecular Pharmaceutics, Purdue University, 575 Stadium Mall Drive, West Lafayette, Indiana 47907, United States.

²Department of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.

³Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.

⁴Metabolite Profiling Facility, Bindley Bioscience Center, Purdue University, 1203 Mitch Daniels Boulevard, West Lafayette, Indiana 47907, United States.

⁵Purdue University Institute for Cancer Research, 201 South University Street, West Lafayette, Indiana 47907, United States.

⁶Department of Comparative Pathobiology, Purdue University, 625 Harrison Street, West Lafayette, Indiana 47907, United States.

⁷Weldon School of Biomedical Engineering, Purdue University, 206 S Martin Jischke Drive, West Lafayette, Indiana 47907, United States.

Corresponding Author : Yoon Yeo

Abstract

Local delivery of immune-activating agents has shown promise in overcoming an immunosuppressive tumor microenvironment (TME) and stimulating antitumor 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 antitumor 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 antitumor immune memory. This study demonstrates the feasibility of systemic immunotherapy using a PLGA NP formulation that delivers ICD-inducing chemotherapy and an immunostimulatory signal.

논문정보

형식Research article
게재일2024년 01월 (BRIC 등록일 2024-01-18)
연구진국외 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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