癌症治疗中棘手的复发和转移带来的挑战导致了各种形式的光动力疗法（PDT）的发展。然而，传统的药物递送系统，如病毒载体、脂质体和聚合物，常常面临药物释放不同步、载体不稳定和循环过程中药物泄漏等问题。为了解决这些问题，我们开发了一种双前药纳米凝胶（PVBN），由与 BSA（牛血清白蛋白）结合的 Pyro（焦脱镁叶绿酸 a）和 SAHA（伏立诺他）组成，有助于药物在溶酶体内同步和自发地原位释放。详细结果表明，PVBN处理的肿瘤细胞表现出ROS和乙酰H3水平升高，导致坏死、凋亡和细胞周期停滞，其中PDT在协同治疗效果中发挥主导作用。此外，PVBN 的抗肿瘤功效在携带黑色素瘤的小鼠中得到验证，它显着抑制肿瘤生长和肺转移。总体而言，我们的双前药纳米凝胶由 SAHA 和 Pyro 与 BSA 结合形成并在溶酶体内释放药物，代表了一种新颖且有前途的增强光化疗临床疗效的策略。版权所有 © 2024 Elsevier B.V. 保留所有权利。

The challenges posed by intractable relapse and metastasis in cancer treatment have led to the development of various forms of photodynamic therapy (PDT). However, traditional drug delivery systems, such as virus vectors, liposomes, and polymers, often suffer from issues like desynchronized drug release, carrier instability, and drug leakage during circulation. To address these problems, we have developed a dual-prodrug nanogel (PVBN) consisting of Pyro (Pyropheophorbide a) and SAHA (Vorinostat) bound to BSA (Bovine Serum Albumin), which facilitates synchronous and spontaneous drug release in situ within the lysosome. Detailed results indicate that PVBN-treated tumor cells exhibit elevated levels of ROS and Acetyl-H3, leading to necrosis, apoptosis, and cell cycle arrest, with PDT playing a dominant role in the synergistic therapeutic effect. Furthermore, the anti-tumor efficacy of PVBN was validated in melanoma-bearing mice, where it significantly inhibited tumor growth and pulmonary metastasis. Overall, our dual-prodrug nanogel, formed by the binding of SAHA and Pyro to BSA and releasing drugs within the lysosome, represents a novel and promising strategy for enhancing the clinical efficacy of photochemotherapy.Copyright © 2024 Elsevier B.V. All rights reserved.