Tannic acid/doxorubicin hybrid nano-assemblies decorated with D-α-tocopheryl polyethylene glycol succinate-conjugated pemetrexed to treat non-small cell lung cancer

IF 5.5 3区工程技术 Q1 ENGINEERING, CHEMICAL

Journal of the Taiwan Institute of Chemical Engineers Pub Date : 2025-04-07 DOI:10.1016/j.jtice.2025.106115

Wei-Jen Huang , Wen-Hsuan Chiang , Hsiang-Yun Chih , I-Ju Liu , Jeng-Sen Tseng , Tsung-Ying Yang

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引用次数: 0

Abstract

Background

The resistance of non-small cell lung cancer (NSCLC) to certain chemotherapy reagents is one of the hurdles to potent lung cancer treatment.

Methods

To amplify the cytotoxicity of doxorubicin (DOX), a frequently utilized chemotherapy drug, against NSCLC, the DOX-encapsulated hybrid nano-assemblies with folate receptor-targeting ability were fabricated using a one-step and organic solvent-free method. The amphiphilic d-α-tocopheryl polyethylene glycol succinate (TPGS) was conjugated with pemetrexed (PEM, folate analog) by esterification. Through the electrostatic and π-π stacking interactions between tannic acid (TA) and DOX, the TA/DOX nano-assemblies were attained and then coated with TPGS-PEM conjugates to obtain TA/DOX@TPGS-PEM nano-assemblies (TDTPNs).

Significant findings

The TDTPNs exhibited a high DOX payload (15.4 wt %) and a well-dispersed spherical shape. Also, the TDTPNs displayed satisfied colloidal stability in the serum-rich milieu and prevented premature DOX leakage. Through folate receptor-mediated endocytosis, the TDTPNs were efficiently internalized by LL/2 cells. Compared to free DOX molecules, the TDTPNs promoted intracellular DOX accumulation upon TPGS-mediated P-glycoprotein inactivation, thus effectively killing LL/2 cells. Furthermore, the TDTPNs exhibited cytotoxicity on LL/2 and PC9 cells superior to TA/DOX@TPGS nano-assemblies (without PEM decoration). These findings indicate that the TDTPNs showed promising potential for enhancing DOX chemotherapy against NSCLC.

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单宁酸/阿霉素杂化纳米复合物修饰D-α-生育酚聚乙二醇琥珀酸偶联培美曲塞治疗非小细胞肺癌

背景非小细胞肺癌（NSCLC）对某些化疗药物的耐药性是有效治疗肺癌的障碍之一。方法为了增强化疗药物多柔比星（DOX）对非小细胞肺癌的细胞毒性，采用一步法制备了具有叶酸受体靶向能力的多柔比星包封的杂化纳米组件。两亲性d-α-生育酚聚乙二醇琥珀酸酯（TPGS）通过酯化反应与培美曲塞（PEM，叶酸类似物）偶联。通过单宁酸（TA）与DOX之间的静电和π-π堆叠相互作用，得到TA/DOX纳米组件，然后涂覆TPGS-PEM共轭物，得到TA/DOX@TPGS-PEM纳米组件（TDTPNs）。TDTPNs表现出高DOX有效载荷（15.4 wt %）和良好分散的球形。此外，TDTPNs在富含血清的环境中表现出良好的胶体稳定性，并防止过早的DOX泄漏。通过叶酸受体介导的内吞作用，TDTPNs被LL/2细胞有效内化。与游离DOX分子相比，TDTPNs通过tpgs介导的p -糖蛋白失活促进细胞内DOX积累，从而有效杀死LL/2细胞。此外，TDTPNs对LL/2和PC9细胞的细胞毒性优于TA/DOX@TPGS纳米组件（没有PEM装饰）。这些发现表明，TDTPNs具有增强DOX化疗治疗NSCLC的潜力。

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来源期刊

Journal of the Taiwan Institute of Chemical Engineers 工程技术-工程：化工

CiteScore

9.10

自引率

14.00%

发文量

362

审稿时长

35 days

期刊介绍： Journal of the Taiwan Institute of Chemical Engineers (formerly known as Journal of the Chinese Institute of Chemical Engineers) publishes original works, from fundamental principles to practical applications, in the broad field of chemical engineering with special focus on three aspects: Chemical and Biomolecular Science and Technology, Energy and Environmental Science and Technology, and Materials Science and Technology. Authors should choose for their manuscript an appropriate aspect section and a few related classifications when submitting to the journal online.