Bao-Toan Nguyen Dang (계명대학교)

한빛사논문

조회155

Bao-Toan Nguyen DangBao-Toan Nguyen Dang

계명대학교

J. Control. Release, Jun 26 2024, S0168-3659(24)00422-X | https://doi.org/10.1016/j.jconrel.2024.06.062 Targeting tumor-associated macrophage with mannosylated nanotherapeutics delivering TLR7/8 agonist enhances cancer immunotherapy

Bao-Toan Nguyen Dang ^a,b, Ramesh Duwa^c,d, Sooyeun Lee ^a, Taeg Kyu Kwon ^e, Jae-Hoon Chang ^f, Jee-Heon Jeong ^b, Simmyung Yook^c,g

^aCollege of Pharmacy, Keimyung University, Daegu 42601, Republic of Korea

^bDepartment of Precision Medicine, School of Medicine, Sungkyunkwan University, Suwon 16419, Republic of Korea

^cDepartment of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon 16419, Republic of Korea

^dDepartment of Radiology, Molecular Imaging Program at Stanford (MIPS), School of Medicine, Stanford University, Stanford, CA 94305, USA

^eDepartment of Immunology, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea

^fCollege of Pharmacy, Yeungnam University, Gyeongbuk 38541, Republic of Korea

^gSchool of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea

Correspondence to: Jee-Heon Jeong, Simmyung Yook

Abstract

Tumor-associated macrophages (TAMs) constitute 50-80% of stromal cells in most solid tumors with high mortality and poor prognosis. Tumor-infiltrating dendritic cells (TIDCs) and TAMs are key components mediating immune responses within the tumor microenvironment (TME). Considering their refractory properties, simultaneous remodeling of TAMs and TIDCs is a potential strategy of boosting tumor immunity and restoring immunosurveillance. In this study, mannose-decorated poly(lactic-co-glycolic acid) nanoparticles loading with R848 (Man-pD-PLGA-NP@R848) were prepared to dually target TAMs and TIDCs for efficient tumor immunotherapy. The three-dimensional (3D) cell culture model can simulate tumor growth as influenced by the TME and its 3D structural arrangement. Consequently, cancer spheroids enriched with tumor-associated macrophages (TAMs) were fabricated to assess the therapeutic effectiveness of Man-pD-PLGA-NP@R848. In the TME, Man-pD-PLGA-NP@R848 targeted both TAMs and TIDCs in a mannose receptor-mediated manner. Subsequently, Man-pD-PLGA-NP@R848 released R848 to activate Toll-like receptors 7 and 8, following dual-reprograming of TIDCs and TAMs. Man-pD-PLGA-NP@R848 could uniquely reprogram TAMs into antitumoral phenotypes, decrease angiogenesis, reprogram the immunosuppressive TME from "cold tumor" into "hot tumor", with high CD4+ and CD8+ T cell infiltration, and consequently hinder tumor development in B16F10 tumor-bearing mice. Therefore, dual-reprograming of TIDCs and TAMs with the Man-pD-PLGA-NP@R848 is a promising cancer immunotherapy strategy.

논문정보

형식Research article
게재일2024년 06월 (BRIC 등록일 2024-06-30)
연구진국내 연구진
분야 의약학 > 약학

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