Folic Acid-Functionalized β-Cyclodextrin for Delivery of Organelle-Targeted Peptide Chemotherapeutics in Cancer.

IF 5.4 3区材料科学 Q2 CHEMISTRY, PHYSICAL

ACS Applied Energy Materials Pub Date : 2024-09-02 Epub Date: 2024-07-28 DOI:10.1021/acs.molpharmaceut.4c00400

Hae Won Ok, Seongeon Jin, Gaeun Park, Batakrishna Jana, Ja-Hyoung Ryu

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Abstract

Recent emphasis on the design of drug delivery systems typically involves the effective transport of a pharmaceutical substance to the disease site with the desired therapeutic efficacy and minimal cytotoxicity. Organelle-targeted peptides have become an integral part of designing an important class of prodrug/prodrug assemblies for new supramolecular therapeutics owing to their favorable biocompatibility, synthetic ease, tunability of their aggregation behavior, and desired functionalization for site-specificity. However, it is still limited due to the low selectivity. We designed a folic acid-functionalized β-cyclodextrin (FA-CD) as a delivery platform for specific and selective delivery of organelle-targeted (such as microtubule, lysosome, and mitochondria) peptide chemotherapeutics to the folate receptor (FR) overexpressing cancer cell lines. Low toxicity was found for the FA-CD and organelle-targeted peptide inclusion complex in FR-negative normal cells, but superior inhibition of tumor growth with no in vivo toxicity was found for the inclusion complex in the xenograft tumor model.

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叶酸功能化β-环糊精用于在癌症中输送细胞器靶向多肽化疗药物

近年来，药物输送系统的设计重点通常是将药物有效地输送到疾病部位，并达到预期的治疗效果和最小的细胞毒性。细胞器靶向肽具有良好的生物相容性、易于合成、聚合行为可调、可进行功能化以实现位点特异性等特点，因此已成为设计新型超分子疗法的一类重要原药/副药组合的组成部分。然而，由于选择性较低，它仍然受到限制。我们设计了一种叶酸官能化的β-环糊精（FA-CD）作为一种递送平台，用于向叶酸受体（FR）过表达的癌细胞系特异性和选择性地递送细胞器靶向（如微管、溶酶体和线粒体）多肽化疗药物。在叶酸受体阴性的正常细胞中，FA-CD 和细胞器靶向多肽包涵复合物的毒性较低，但在异种移植肿瘤模型中，包涵复合物对肿瘤生长有很好的抑制作用，且无体内毒性。

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来源期刊

ACS Applied Energy Materials Materials Science-Materials Chemistry

CiteScore

10.30

自引率

6.20%

发文量

1368

期刊介绍： ACS Applied Energy Materials is an interdisciplinary journal publishing original research covering all aspects of materials, engineering, chemistry, physics and biology relevant to energy conversion and storage. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrate knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important energy applications.