磁性纳米粒子介导的多模式癌症疗法:热疗、可控药物释放和基于抗体的精准治疗

IF 3.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Advanced Therapeutics Pub Date : 2024-07-29 DOI:10.1002/adtp.202400168
S. S. Pawar, O. Selyshchev, L. Rasabathina, O. Hellwig, V. V. Kedage, D.R.T. Zahn, V. Stephan, B. Kersting, G. Salvan, A. D. Chougale, P.B. Patil
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摘要

癌症疗法研究进展迅速,需要探索创新方法来进一步提高治疗效果。本文报告了一种结合生物活性靶向、磁热和药物控释的多模式癌症治疗方法。为此,通过将 CA 15-3 抗体与负载多柔比星的功能化磁性纳米粒子(MNPs)共轭,生物工程设计了一种纳米制剂 MNP-Chi-Dox-Ab。溶液热合成的 MNPs 具有均匀的球形形状和大小,并被热-pH 响应壳聚糖功能化。与生理 pH 值和温度下的药物释放率相比,该纳米制剂在 pH 值为 5 和温度为 42 ℃ 时的药物释放率更高(≈65%)。此外,在交变磁场中,药物释放量提高了 74%。在 MCF-7 乳腺癌细胞中进行的细胞毒性研究证实了纳米制剂的主动靶向潜力。不含生物活性分子(抗-CA 15-3)的纳米制剂只有 18% 的癌细胞死亡,而缀合了抗-CA 15-3 的纳米制剂则有 43% 的细胞死亡。流式细胞术研究表明,与生理温度相比,超高温(42 °C)下的细胞凋亡数量有所增加。这些结果表明,MNP-Chi-Dox-Ab 纳米制剂是一种很有前景的多模式平台,它将活性靶向、药物控释和热疗结合在一起,可用于乳腺癌的协同治疗。
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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Magnetic Nanoparticle-Mediated Multimodal Cancer Therapy: Hyperthermia, Controlled Drug Release, and Antibody-Based Precision

Research in cancer therapies is rapidly advancing and demands the exploration of innovative approaches to further improve the efficacy of treatment. Here a multimodal approach for cancer therapy is reported which combines bioactive targeting, magnetic hyperthermia, and controlled drug release. For this, a nanoformulation MNP-Chi-Dox-Ab, is bioengineered by conjugating CA 15-3 antibodies to doxorubicin-loaded functionalized magnetic nanoparticles (MNPs). Solvothermally synthesized MNPs of uniform spherical shape and size are functionalized with thermo-pH-responsive chitosan. The nanoformulation showed higher drug release of ≈65% at pH 5 and 42 °C temperature compared to the release at physiological pH and temperature. Furthermore, in an alternating magnetic field drug release is enhanced to 74%. Cytotoxicity studies in MCF-7 breast cancer cells confirm the active targeting potential of the nanoformulation. For the nanoformulation without bioactive molecule (anti-CA 15-3) only 18% cancer cell death is noted whereas with the conjugation of anti-CA 15-3, 43% cell death is recorded. Flow cytometry studies revealed an increased apoptotic population at hyperthermic temperature (42 °C) compared to the physiological temperature. These results suggest that MNP-Chi-Dox-Ab nanoformulation represents a promising multimodal platform for synergistic breast cancer therapy by combining active targeting, controlled drug release, and hyperthermia.

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来源期刊
Advanced Therapeutics
Advanced Therapeutics Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
7.10
自引率
2.20%
发文量
130
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