Abstract：
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.
摘要：
癌症治疗中顽固性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,传统的药物输送系统，如病毒载体，脂质体，和聚合物，经常遭受诸如去同步药物释放之类的问题，载波不稳定性，和药物在循环过程中泄漏。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（Pyrophohorbidea）和SAHA（Vorinostat）组成，这有助于在溶酶体内原位同步和自发的药物释放。详细的结果表明，PVBN处理的肿瘤细胞表现出升高水平的ROS和乙酰-H3，导致坏死，凋亡，和细胞周期停滞，PDT在协同治疗作用中起主导作用。此外，PVBN的抗肿瘤功效在携带黑色素瘤的小鼠中得到验证，显著抑制肿瘤生长和肺转移.总的来说,我们的双前药纳米凝胶，通过SAHA和Pyro与BSA结合并在溶酶体内释放药物而形成，代表了提高光化学疗法临床疗效的新颖且有前途的策略。
