Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea.
Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER) Kolkata, Mohanpur 741246, India.
Mol Pharm. 2024 Sep 2;21(9):4498-4509. doi: 10.1021/acs.molpharmaceut.4c00400. Epub 2024 Jul 28.
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.
近年来，药物传递系统的设计重点通常涉及将药物物质有效递送到疾病部位，以达到所需的治疗效果和最小的细胞毒性。由于其良好的生物相容性、易于合成、聚集行为的可调变性以及对靶向性的期望功能化，靶向细胞器的肽已成为设计新型超分子治疗药物的前药/前药组装体的重要组成部分。然而，由于选择性低，其应用仍然受到限制。我们设计了一种叶酸功能化的β-环糊精（FA-CD）作为递药平台，用于将靶向细胞器（如微管、溶酶体和线粒体）的肽化疗药物特异性和选择性地递送到叶酸受体（FR）过表达的癌细胞系。在 FR 阴性的正常细胞中，FA-CD 和靶向细胞器的肽包合物的毒性较低，但在异种移植肿瘤模型中，包合物对肿瘤生长的抑制作用优于体内毒性。
