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J. Control. Release, Available online 24 February 2025 | https://doi.org/10.1016/j.jconrel.2025.02.072 Breaking barriers: Nitric oxide-releasing nanocomplexes for collagen degradation and enhanced αPD-L1 immunotherapy in deep tumor

Jihye Lee¹, Hyoeun Cho¹, Jieun Kim, Junha Lim, Yeoul Kang, Won Jong Kim

Department of Chemistry, POSTECH-CATHOLIC Biomedical Engineering Institute (POSTECH), Pohang 37673, South Korea

¹These authors contributed equally.
Corresponding author : Won Jong Kim

Abstract

Overcoming the physical barrier of the extracellular matrix (ECM) surrounding tumors is a critical challenge in achieving effective immune checkpoint blockade (ICB). The dense ECM impedes the infiltration of immune checkpoint inhibitors (ICIs) and cytotoxic T lymphocytes (CTLs) into tumor tissues. To address this, we design a nanocomplex incorporating a reactive oxygen species (ROS)-responsive nitric oxide (NO) prodrug around TANNylated αPD-L1. Within the tumor microenvironment (TME), this nanocomplex accumulates and selectively releases NO in response to ROS. The released NO activates matrix metalloproteinases (MMPs) in the ECM, leading to collagen degradation. Following this, the pH-responsive release of αPD-L1 in the deeper tumor regions ensures effective delivery, allowing CTLs to penetrate the tumor more efficiently by bypassing the ECM barrier, thereby enhancing immunotherapy. Overall, this study applies a nanocomplex capable of releasing NO and αPD-L1 in the tumor to a solid tumor model, successfully inhibiting tumor growth by altering the immunosuppressive environment through improved penetration.

논문정보

형식Research article
게재일2025년 02월 (BRIC 등록일 2025-02-26)
연구진국내 연구진
분야 바이오·의료융합 > 바이오소재

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