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J. Control. Release, Volume 369, May 2024, Pages 351-362 | https://doi.org/10.1016/j.jconrel.2024.03.046 Tumor-targeted and stimulus-responsive polymeric prodrug nanoparticles to enhance the anticancer therapeutic efficacy of doxorubicin

Nuri Kim ^a, Soonyoung Kwon^a, Gayoung Kwon ^a, Nanhee Song ^a, Hanui Jo ^a, Chunho Kim ^b, Sangjun Park ^b, Dongwon Lee ^a,c

^aDepartment of Bionanotechnology and Bioconvergence Engineering, Jeonbuk National University, Jeonju, Jeonbuk 54896, Republic of Korea

^bResearch Institute of Radiological & Medical Sciences, Korea Institute of Radiological & Medical Sciences, Nowongu, Seoul 01812, Republic of Korea

^cDepartment of Polymer⋅ Nano Science and Technology, Jeonbuk National University, Jeonju, Jeonbuk 54896, Republic of Korea

Corresponding author : Dongwon Lee

Abstract

Polymeric prodrug nanoparticles have gained increasing attention in the field of anticancer drug delivery because of their dual functions as a drug carrier and a therapeutic agent. Doxorubicin (DOX) is a highly effective chemotherapeutic agent for various cancers but causes cardiotoxicity. In this work, we developed polymeric prodrug (pHU) nanoparticles that serve as both a drug carrier of DOX and a therapeutic agent. The composition of pHU includes antiangiogenic hydroxybenzyl alcohol (HBA) and ursodeoxycholic acid (UDCA), covalently incorporated through hydrogen peroxide (H ₂O ₂)-responsive peroxalate. To enhance cancer cell specificity, pHU nanoparticles were surface decorated with taurodeoxycholic acid (TUDCA) to facilitate p-selectin-mediated cancer targeting. TUDCA-coated and DOX-loaded pHU nanoparticles (t-pHUDs) exhibited controlled release of DOX triggered by H ₂O ₂, characteristic of the tumor microenvironment. t-pHUDs also effectively suppressed cancer cell migration and vascular endothelial growth factor (VEGF) expression in response to H ₂O ₂. In animal studies, t-pHUDs exhibited highly potent anticancer activity. Notably, t-pHUDs, with their ability to accumulate preferentially in tumors due to the p-selectin targeting, surpassed the therapeutic efficacy of equivalent DOX and pHU nanoparticles alone. What is more, t-pHUDs significantly suppressed VEGF expression in tumors and mitigated hepato- and cardiotoxicity of DOX. Given their cancer targeting ability, enhanced therapeutic efficacy and minimized off-target toxicity, t-pHUDs present an innovative and targeted approach with great translational potential as an anticancer therapeutic agent.

논문정보

형식Research article
게재일2024년 05월 (BRIC 등록일 2024-04-15)
연구진국내 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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