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利用同时响应温度和 pH 值的纳米杂化实现癌症化疗药物的载入和释放。

Loading and release of cancer chemotherapy drugs utilizing simultaneous temperature and pH-responsive nanohybrid.

机构信息

Computational Biology and Chemistry Group (CBCG), Universal Scientific Education and Research Network (USERN), Tehran, Iran.

Student Research Committee, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

BMC Pharmacol Toxicol. 2021 Jul 14;22(1):41. doi: 10.1186/s40360-021-00508-8.

Abstract

BACKGROUND

Recently, the development of nanocarriers and the improvement of their biochemical properties have became of great importance. Single-walled carbon nanotubes (SWCNT) have many applications in drug delivery systems (DDS) as a common carbon-based structure. In the current work, the penetration, co-loading, and co-release of Doxorubicin (DOX) and Paclitaxel (PAX), as two cancer chemotherapy agents, were investigated using a novel modified copolymer with functionalized SWCNT.

RESULTS

This study proposes a dual-responsive smart carrier that is sensitive to pH and temperature. The carrier consists of functionalized SWNT and Dimethyl acrylamide-trimethyl chitosan (DMAA-TMC) grafting on SWCNT. This suggested carrier was investigated by utilizing molecular simulations. Interaction energies between DOX, PAX, and carrier as well as the affinity of drugs to the nanocarrier were studied. The energy analysis of drug release and adsorption presented that DOX and PAX delivery using this carrier is selective and sensitive at healthy and cancerous conditions. The attraction of DMAA-TMC, as a biodegradable and biocompatible copolymer, with SWCNT showed that degradation mechanism in acidic environment deformed the copolymer. This leads to a smart release mechanism in an acidic cancerous tissue. Additionally, it improves hydrophilicity, optimum nano-particle size, and cell cytotoxicity concerns.

CONCLUSIONS

The simulation results manifested a significant contribution of DMAA-TMC in the adsorption and release of cancer chemotherapy drugs in normal and neoplastic tissues. The interaction of copolymer also improves the biocompatibility and biodegradability of the SWCNT. Smart drug delivery carrier can be a valuable nanohybrid for loading, transporting, and releasing of cancer chemotherapy drugs.

摘要

背景

最近,纳米载体的发展及其生化性能的提高变得至关重要。单壁碳纳米管(SWCNT)作为一种常见的碳基结构,在药物传递系统(DDS)中有许多应用。在目前的工作中,通过一种新型的功能化 SWCNT 改性共聚物,研究了阿霉素(DOX)和紫杉醇(PAX)这两种癌症化疗药物的渗透、共载和共释放。

结果

本研究提出了一种对 pH 值和温度双重敏感的智能载体。该载体由功能化的 SWNT 和 DMAA-TMC 接枝在 SWCNT 上组成。利用分子模拟研究了该载体。研究了 DOX、PAX 与载体之间的相互作用能以及药物与纳米载体的亲和力。药物释放和吸附的能量分析表明,该载体对健康和癌变条件下 DOX 和 PAX 的输送具有选择性和敏感性。DMAA-TMC 作为一种可生物降解和生物相容的共聚物与 SWCNT 的吸引力表明,在酸性环境中的降解机制使共聚物变形。这导致了在酸性癌组织中的智能释放机制。此外,它提高了亲水性、最佳纳米颗粒尺寸和细胞细胞毒性问题。

结论

模拟结果表明,DMAA-TMC 对正常和肿瘤组织中癌症化疗药物的吸附和释放有重要贡献。共聚物的相互作用也提高了 SWCNT 的生物相容性和生物降解性。智能药物输送载体可以作为负载、输送和释放癌症化疗药物的有价值的纳米杂化物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d7f/8278666/1f0a860bba36/40360_2021_508_Fig1_HTML.jpg

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