Wu Qiwei, Ma Xiaodong, Zhou Wenhui, Yu Rong, Rosenholm Jessica M, Tian Weizhong, Zhang Lirong, Wang Dongqing, Zhang Hongbo
Department of Radiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, China.
Department of Medical Imaging, Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou 225300, China.
Pharmaceutics. 2022 Oct 25;14(11):2280. doi: 10.3390/pharmaceutics14112280.
Pancreatic carcinoma is an aggressive subtype of cancer with poor prognosis, known for its refractory nature. To address this challenge, we have established a stable nanoplatform that combines chemotherapy with photodynamic therapy (PDT) to achieve better curative efficacy. First, we designed and synthesized a disulfide-bonded paclitaxel (PTX)-based prodrug, which was further mixed with gemcitabine (GEM) and photosensitizer THPP in an optimized ratio. Subsequently, the mixture was added dropwise into amphiphilic polymer DSPE-PEG water solution to form micelles composed of DSPE-PEG nanoparticles (TPG NPs). The TPG NPs were around 135 nm, and showed great ability of DTT stimulated release of PTX and GEM. Moreover, the TPG NPs can be efficiently uptaken by pancreatic cancer PANC-1 cells and effectively kill them, especially when combined with 650 nm laser irradiation. Finally, the TPG NPs have shown enhanced long-term circulation ability and also exhibited efficient anti-tumor activity in combination with 650 nm laser irradiation in a pancreatic cancer mouse model. In summary, the designed TPG NPs possesses great potential for co-delivery of paclitaxel prodrug, GEM and THPP, which enables combined chemo-photodynamic therapy for cancer treatment. In addition, the stimulated release of PTX prodrug and GEM also allows for better targeting of tumor cells and the increased therapeutic effect against cancer cells. Overall, the TPG NPs can serve as a good candidate for pancreatic cancer treatment.
胰腺癌是一种侵袭性癌症亚型，预后较差，以其难治性著称。为应对这一挑战，我们建立了一种稳定的纳米平台，将化疗与光动力疗法（PDT）相结合以实现更好的治疗效果。首先，我们设计并合成了一种基于二硫键连接的紫杉醇（PTX）前药，将其与吉西他滨（GEM）和光敏剂四苯基卟啉（THPP）按优化比例进一步混合。随后，将该混合物逐滴加入两亲性聚合物二硬脂酰磷脂酰乙醇胺-聚乙二醇（DSPE-PEG）水溶液中，形成由DSPE-PEG纳米颗粒组成的胶束（TPG NPs）。TPG NPs粒径约为135 nm，表现出二硫苏糖醇（DTT）刺激释放PTX和GEM的强大能力。此外，TPG NPs能够被胰腺癌PANC-1细胞有效摄取并有效杀死它们，尤其是在结合650 nm激光照射时。最后，TPG NPs在胰腺癌小鼠模型中显示出增强的长期循环能力，并且在结合650 nm激光照射时也表现出高效的抗肿瘤活性。总之，所设计的TPG NPs在共递送紫杉醇前药、GEM和THPP方面具有巨大潜力，能够实现联合化学-光动力疗法治疗癌症。此外，PTX前药和GEM的刺激释放还能更好地靶向肿瘤细胞并增强对癌细胞的治疗效果。总体而言，TPG NPs可作为胰腺癌治疗的良好候选物。
