Plectin-1-targeted recognition for enhancing comprehensive therapy in pancreatic ductal adenocarcinoma,Nanoscale

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Plectin-1-targeted recognition for enhancing comprehensive therapy in pancreatic ductal adenocarcinoma
Nanoscale ( IF 5.8 ) Pub Date : 2024-09-11 , DOI: 10.1039/d4nr01587h
Qing Zhu _{1,

2} , Silue Zeng _{1,

2} , Junying Yang _{1,

2} , Jiaming Zhuo _{1,

2} , Peifeng Wang _{1,

2} , Sai Wen _{1,

2} , Chihua Fang _{1,

2}

Affiliation

Pancreatic ductal adenocarcinoma (PDAC) poses a formidable challenge due to its aggressive nature and poor prognosis. Gemcitabine (Gem), a primary therapeutic option, functions by inhibiting DNA synthesis and promoting apoptosis, thereby impeding the progression of PDAC. However, Gem is hindered by suboptimal pharmacokinetics and efficacy. In response to these challenges, we have developed a nanoparticle (NP) designed for specific recognition of plectin-1 in PDAC cell membranes. The NPs encapsulate Gem while demonstrating pH-responsive drug release characteristics in the acidic tumor microenvironment. This targeted approach enhances local drug delivery while alleviating concerns about systemic toxicity. Furthermore, the NPs are enriched with indocyanine green (ICG), renowned for its strong photothermal effects, thereby further enhancing therapeutic outcomes. This study presents an innovative therapeutic strategy for PDAC based on a plectin-1-targeted recognition delivery approach. The approach is applied to enhance chemotherapy, combined with photothermal therapy (PTT), inducing apoptosis in PDAC cell lines and improving the pharmacokinetics of Gem. In conclusion, the delivery strategy based on plectin-1-targeted recognition shows promising preclinical prospects for enhancing therapeutic efficacy in PDAC, offering valuable insights for future clinical applications.

中文翻译：

Plectin-1 靶向识别增强胰腺导管腺癌的综合治疗

胰腺导管腺癌（PDAC）由于其侵袭性和不良预后而构成了艰巨的挑战。吉西他滨（Gem）是一种主要的治疗选择，通过抑制 DNA 合成和促进细胞凋亡发挥作用，从而阻止 PDAC 的进展。然而，Gem 受到次优药代动力学和疗效的阻碍。为了应对这些挑战，我们开发了一种纳米颗粒（NP），旨在特异性识别 PDAC 细胞膜中的 plectin-1。NPs 封装了 Gem，同时在酸性肿瘤微环境中表现出 pH 反应性的药物释放特性。这种有针对性的方法增强了局部药物递送，同时减轻了对全身毒性的担忧。此外，NP 富含吲哚菁绿（ICG），以其强大的光热效应而闻名，从而进一步提高治疗效果。本研究提出了一种基于 plectin-1 靶向识别递送方法的 PDAC 创新治疗策略。该方法用于增强化疗，结合光热疗法（PTT），诱导 PDAC 细胞系细胞凋亡并改善 Gem 的药代动力学。总之，基于 plectin-1 靶向识别的递送策略在增强 PDAC 治疗效果方面显示出良好的临床前前景，为未来的临床应用提供了有价值的见解。

更新日期：2024-09-11

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