Strategies for Peptide-Mediated Cargo Delivery to Human Smooth Muscle Cells.
Strategies for Peptide-Mediated Cargo Delivery to Human Smooth Muscle Cells.
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肽介导的货物递送至人类平滑肌细胞的策略。
DOI：
10.1007/978-1-0716-1752-6_29
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Gurney L
中科院分区：
文献类型：
--
作者：
Gurney L
涉及平滑肌细胞功能障碍的疾病带来了重大的健康和社会经济负担，并且对标准治疗策略仍然具有顽固的抵抗力。例如许多心血管疾病和自发性早产，这种并发症影响着全世界 11% 的妊娠。这推动了对治疗这些疾病的新药物输送策略的持续探索。为此目的使用细胞穿透肽（CPP）仍然是一个有前途的探索途径，尽管尚未实现。在某种程度上，这可能与缺乏研究 CPP 作为药物输送载体对人类平滑肌细胞和组织的应用有关。我们试图通过报告检查不同 CPP 货物载体对人类子宫和血管平滑肌细胞的摄取的方法来解决这一知识差距。特别是，我们在此报告 (a) 四种不同的 CPP-荧光团缀合物，跨度为 1309–3435 Da，净电荷为 +2 至 +7，可以递送至人分离的子宫平滑肌细胞，而不诱导细胞毒性； (b) 此类 CPP 递送的货物可以是荧光部分和/或生物活性肽； (c)可以在短时间内将CPP递送至离体人体组织中的天然平滑肌细胞。进一步探索 CPP 作为促进靶向药物递送至天然人类平滑肌组织的工具，将有助于提高我们对涉及平滑肌功能障碍的重大疾病的科学机制的理解，并促进治疗研究。
Diseases involving dysfunction of smooth muscle cells present a major health and socioeconomic burden, and have remained stubbornly resistant to standard therapeutic strategies. Examples include many cardiovascular diseases and spontaneous preterm birth, a complication affecting up to 11% of all pregnancies worldwide. This fuels the continued search for new drug delivery strategies to treat these conditions. The use of cell penetrating peptides (CPPs) for this purpose remains a promising, if as yet unrealized, avenue to explore. In part, this may relate to a paucity of studies investigating the application of CPPs as drug delivery vectors tohumansmooth muscle cells and tissues. We have sought to address this knowledge gap by reporting methods for examining the uptake of different CPP-cargo vectors to human uterine and vascular smooth muscle cells. In particular, we report here (a) that four different CPP-fluorophore conjugates, spanning masses of 1309–3435 Da, and net charges of +2 to +7, can be delivered to human isolated uterine smooth muscle cells without inducing cell toxicity; (b) that the cargo delivered by such CPPs can be fluorescent moieties and/or biologically active peptides; (c) that CPP delivery in a short time frame to native smooth muscle cells in human tissues ex vivo can be achieved. Further exploration of CPPs as tools to facilitate targeted drug delivery to native human smooth muscle tissues will assist in improving our understanding of scientific mechanisms underlying major diseases involving smooth muscle dysfunction as well as facilitating therapeutic investigations.
DOI：
10.1093/med/9780198794684.003.0029
发表时间：
2018
期刊：
Oxford Textbook of Global Health of Women, Newborns, Children, and Adolescents
影响因子：
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作者：
S. Moxon;Samantha Sadoo;T. Lissauer
通讯作者：
T. Lissauer
剖腹产时进行人类子宫肌层取样安全吗？
影响因子：
9.8
作者：
S. McElvy;M. Miodovnik;L. Myatt;J. Khoury;T. Siddiqi
通讯作者：
T. Siddiqi