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利用胆固醇功能化环糊精纳米海绵增强癌细胞中的药物递送

Leveraging Cholesterol-Functionalized Cyclodextrin Nanosponges for Enhanced Drug Delivery in Cancer Cells.

作者信息

Krabicová Ilona, Khazaei Monfared Yousef, Caldera Fabrizio, Mahmoudian Mohammad, Hobbs Christopher, Santalucia Rosangela, Appleton Silvia Lucia, Matencio Adrián, Zakeri-Milani Parvin, Trotta Francesco

机构信息

Department of Chemistry, Faculty of Science, Humanities and Education, Technical University of Liberec, 461 17 Liberec, Czech Republic.

Department of Chemistry, University of Turin, 10125 Turin, Italy.

出版信息

Int J Mol Sci. 2025 Jan 30;26(3):1213. doi: 10.3390/ijms26031213.

DOI:10.3390/ijms26031213
PMID:39940979
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11818590/
Abstract

Cholesterol, the essential building block of cellular membranes, has proven to be a useful tool for increasing the biocompatibility and bioavailability of drug delivery systems in cancer treatment. Resveratrol, a natural polyphenolic compound with promising anticancer properties, faces significant limitations due to its low solubility and bioavailability, hindering its clinical utility. Therefore, in the present study, we aimed to design cholesterol-functionalized cyclodextrin nanosponges (Chol-NSs) with a tunable cholesterol content to optimize resveratrol encapsulation and delivery. Both formulations, free carbonyl diimidazole (CDI) NSs and functionalized Chol-NSs, demonstrated high drug loading and encapsulation efficiency. In vitro experiments revealed that cholesterol incorporation significantly improved the cellular uptake of nanocarriers and potentiated the cytotoxic effects of resveratrol on breast cancer cells. Importantly, both free CDI NSs and functionalized Chol-NSs, even at varying cholesterol percentages, demonstrated a safe profile against both fibroblast and breast cancer cell lines. These results indicate that cholesterol-functionalized nanosponges represent a promising platform for the effective and safe delivery of natural compounds in cancer therapy.

摘要

胆固醇作为细胞膜的重要组成部分，已被证明是提高癌症治疗中药物递送系统生物相容性和生物利用度的有用工具。白藜芦醇是一种具有潜在抗癌特性的天然多酚化合物，由于其低溶解度和生物利用度而面临重大限制，阻碍了其临床应用。因此，在本研究中，我们旨在设计具有可调节胆固醇含量的胆固醇功能化环糊精纳米海绵（Chol-NSs），以优化白藜芦醇的包封和递送。游离羰基二咪唑（CDI）纳米海绵和功能化Chol-NSs这两种制剂均显示出高载药量和包封效率。体外实验表明，胆固醇的掺入显著提高了纳米载体的细胞摄取，并增强了白藜芦醇对乳腺癌细胞的细胞毒性作用。重要的是，游离CDI纳米海绵和功能化Chol-NSs，即使在不同的胆固醇百分比下，对成纤维细胞和乳腺癌细胞系均显示出安全的特性。这些结果表明，胆固醇功能化纳米海绵是癌症治疗中有效和安全递送天然化合物的有前景的平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57f7/11818590/1923f58d5712/ijms-26-01213-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57f7/11818590/a135a8c154f8/ijms-26-01213-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57f7/11818590/e33f905b3903/ijms-26-01213-sch001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57f7/11818590/bfdcd782445e/ijms-26-01213-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57f7/11818590/7f413588433b/ijms-26-01213-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57f7/11818590/d7fa65df5799/ijms-26-01213-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57f7/11818590/5f0496fd6f28/ijms-26-01213-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57f7/11818590/1923f58d5712/ijms-26-01213-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57f7/11818590/a135a8c154f8/ijms-26-01213-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57f7/11818590/e33f905b3903/ijms-26-01213-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57f7/11818590/7e15c5ceb558/ijms-26-01213-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57f7/11818590/12cabafd4b35/ijms-26-01213-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57f7/11818590/bfdcd782445e/ijms-26-01213-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57f7/11818590/7f413588433b/ijms-26-01213-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57f7/11818590/d7fa65df5799/ijms-26-01213-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57f7/11818590/5f0496fd6f28/ijms-26-01213-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57f7/11818590/1923f58d5712/ijms-26-01213-g008.jpg

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