State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, And Collaborative Innovation Center of Biotherapy, Chengdu, 610041, PR China; Laboratory of Heart Valve Disease, West China Hospital, Sichuan University, Chengdu, 610041, PR China.
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, And Collaborative Innovation Center of Biotherapy, Chengdu, 610041, PR China; West China School of Nursing/West China Hospital, Sichuan University, Chengdu, 610041, PR China.
Biomaterials. 2023 Feb;293:121975. doi: 10.1016/j.biomaterials.2022.121975. Epub 2022 Dec 20.
Bladder cancer is one of the most common malignant tumors in the urinary system worldwide. The poor permeability and uncontrollable release of drug and hypoxia of tumor tissues were the main reasons leading to poor therapeutic effect of chemo-photodynamic therapy for bladder cancer. To solve the above problems, a tumor-targeting peptide Arg-Gly-Asp (RGD) modified platinum nanozyme (PtNP) co-loaded glutathione (GSH)-responsive prodrug nanoparticles (PTX-SS-HPPH/Pt@RGD-NP) was constructed. Firstly, a GSH-responsive prodrug (PTX-SS-HPPH) was prepared by introducing a disulfide bond between paclitaxel (PTX) and photosensitizer 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH), which could realize the GSH-responsive release of the drug at the tumor sites. Also, the distearoylphosphoethanolamine-poly (ethylene glycol)-RGD peptide (DSPE-PEG-RGD) modified the prodrug to enhance the targeting and permeability ability to bladder cancer cells. Besides, to alleviate the hypoxia of tumor tissues, PtNP was introduced to produce oxygen (O) and improve photodynamic therapy efficiency. The results showed that the PTX-SS-HPPH/Pt@RGD-NP could achieve GSH-responsive drug release in tumor microenvironment, enhance the drug accumulation time and permeability at tumor sites in T24 subcutaneous tumor model and T24 orthotopic bladder tumor model, and alleviate hypoxia in tumor tissues, thus realizing enhanced chemo-photodynamic therapy for bladder cancer, and providing new strategies and methods for clinical treatment of bladder cancer.
膀胱癌是全球泌尿系统最常见的恶性肿瘤之一。药物渗透性差、释放不可控以及肿瘤组织缺氧是导致膀胱癌化学-光动力疗法疗效不佳的主要原因。为了解决上述问题，构建了一种肿瘤靶向肽 Arg-Gly-Asp（RGD）修饰的载铂纳米酶（PtNP）共载谷胱甘肽（GSH）响应前药纳米颗粒（PTX-SS-HPPH/Pt@RGD-NP）。首先，通过在紫杉醇（PTX）和光敏剂 2-（1-己氧基乙基）-2-去乙烯基焦脱镁叶绿酸-a（HPPH）之间引入二硫键，制备了一种 GSH 响应前药（PTX-SS-HPPH），可以在肿瘤部位实现药物的 GSH 响应释放。此外，将二硬脂酰基磷脂酰乙醇胺-聚（乙二醇）-RGD 肽（DSPE-PEG-RGD）修饰前药以增强对膀胱癌细胞的靶向性和通透性。此外，为了缓解肿瘤组织缺氧，引入了 PtNP 以产生氧气（O）并提高光动力治疗效率。结果表明，PTX-SS-HPPH/Pt@RGD-NP 可以在肿瘤微环境中实现 GSH 响应药物释放，增强 T24 皮下肿瘤模型和 T24 原位膀胱癌模型中肿瘤部位的药物蓄积时间和通透性，并缓解肿瘤组织缺氧，从而实现膀胱癌的增强化学-光动力治疗，为膀胱癌的临床治疗提供了新的策略和方法。
