Dual-targeted and esterase-responsive cyclodextrin-based host-guest nanocomposites for enhanced antitumor therapy

IF 5.4 2区医学 Q1 BIOPHYSICS Colloids and Surfaces B: Biointerfaces Pub Date : 2024-11-08 DOI:10.1016/j.colsurfb.2024.114371

Li Qin , Jianfei Tu , Jiawei Zhao , Yuanke Zhang , Tiancheng Li , Yuqi Zhang , Peng Zhang , Guixia Ling , Jiansong Ji

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Abstract

Conventional chemotherapy drugs are difficult to effectively target tumor tissue, leading to poor treatment outcomes and side effects. Actively targeted and stimuli-responsive nanomedicine greatly improves this situation, allowing for more precise drug accumulation at tumor sites. Herein, carboxymethyl-β-cyclodextrin (CMCD) - based host-guest nanocomposites (NPs) encapsulating hydroxycamptothecin (HCPT) were fabricated, which responded to esterase and had the function of targeting CD 44 receptors and the nucleus. PS-CMCD was firstly synthesized through an amide reaction of protamine (PS) and CMCD to enhance the function of penetrating membrane and nuclear localization. PS-CMCD/HCPT/HA NPs were then prepared by the host-guest complexation of PS-CMCD and HCPT and followed by surface modification of hyaluronic acid (HA) with CD44 receptor-targeting properties. The successful inclusion was also validated through computer simulation. The obtained nanocomposites displayed the esterase-responsive release behaviors of HCPT. Moreover, the synthesized PS-CMCD/HCPT/HA NPs enhanced the intracellular drug uptake due to the tumor cell- and nuclear-mediated targeting. In addition, in vivo application exhibited that PS-CMCD/HCPT/HA NPs realized good antitumor effects. These findings suggested its potential for targeted delivery and more effective tumor therapy.

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用于增强抗肿瘤治疗的双靶向和酯酶响应环糊精基主客纳米复合材料

传统化疗药物难以有效靶向肿瘤组织，导致治疗效果不佳和副作用。而具有主动靶向性和刺激响应性的纳米药物可大大改善这一状况，使药物更精确地在肿瘤部位蓄积。本文制备了基于羧甲基-β-环糊精（CMCD）的主-客纳米复合材料（NPs），其中封装了羟基喜树碱（HCPT），对酯酶有反应，并具有靶向CD 44受体和细胞核的功能。首先通过原胺（PS）和CMCD的酰胺反应合成了PS-CMCD，以增强其穿膜和核定位功能。PS-CMCD/HCPT/HA NPs的制备是通过PS-CMCD和HCPT的主客体复合物，然后在表面修饰具有CD44受体靶向特性的透明质酸（HA）。计算机模拟也验证了这种成功的结合。所获得的纳米复合材料显示了 HCPT 的酯酶响应释放行为。此外，合成的 PS-CMCD/HCPT/HA NPs 通过肿瘤细胞和核介导的靶向作用提高了细胞内的药物吸收。此外，体内应用表明 PS-CMCD/HCPT/HA NPs 具有良好的抗肿瘤效果。这些研究结果表明，PS-CMCD/HCTT/HA NPs具有靶向递送和更有效治疗肿瘤的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Colloids and Surfaces B: Biointerfaces 生物-材料科学：生物材料

CiteScore

11.10

自引率

3.40%

发文量

730

审稿时长

42 days

期刊介绍： Colloids and Surfaces B: Biointerfaces is an international journal devoted to fundamental and applied research on colloid and interfacial phenomena in relation to systems of biological origin, having particular relevance to the medical, pharmaceutical, biotechnological, food and cosmetic fields. Submissions that: (1) deal solely with biological phenomena and do not describe the physico-chemical or colloid-chemical background and/or mechanism of the phenomena, and (2) deal solely with colloid/interfacial phenomena and do not have appropriate biological content or relevance, are outside the scope of the journal and will not be considered for publication. The journal publishes regular research papers, reviews, short communications and invited perspective articles, called BioInterface Perspectives. The BioInterface Perspective provide researchers the opportunity to review their own work, as well as provide insight into the work of others that inspired and influenced the author. Regular articles should have a maximum total length of 6,000 words. In addition, a (combined) maximum of 8 normal-sized figures and/or tables is allowed (so for instance 3 tables and 5 figures). For multiple-panel figures each set of two panels equates to one figure. Short communications should not exceed half of the above. It is required to give on the article cover page a short statistical summary of the article listing the total number of words and tables/figures.