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用于按需向癌细胞递送siRNA治疗剂的ROS响应型二茂铁基两亲性聚酰胺-胺树枝状大分子

ROS-Responsive Ferrocenyl Amphiphilic PAMAM Dendrimers for On-Demand Delivery of siRNA Therapeutics to Cancer Cells.

作者信息

Chen Peng, Wang Zhihui, Wang Xinmo, Gong Junni, Sheng Ju, Pan Yufei, Zhu Dandan, Liu Xiaoxuan

机构信息

Center of Advanced Pharmaceuticals and Biomaterials, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China.

出版信息

Pharmaceutics. 2024 Jul 13;16(7):936. doi: 10.3390/pharmaceutics16070936.

DOI:10.3390/pharmaceutics16070936
PMID:39065632
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11280363/
Abstract

Small interfering RNA (siRNA) therapeutics, characterized by high specificity, potency, and durability, hold great promise in the treatment of cancer and other diseases. However, the clinic implementation of siRNA therapeutics critically depends on the safe and on-demand delivery of siRNA to the target cells. Here, we reported a family of ferrocenyl amphiphilic dendrimers () for on-demand delivery of siRNA in response to the high ROS content in cancer cells. These dendrimers bear ROS-sensitive ferrocene moieties in the hydrophobic components and positively chargeable poly(amidoamine) dendrons as the hydrophilic entities, possessing favorable safety profiles and ROS responsive properties. One of these ferrocenyl amphiphilic dendrimers, , outperforms in siRNA delivery, benefiting from its optimal balance of hydrophobicity and hydrophilicity. Its ROS feature facilitates specific and efficient disassembly of its complex with siRNA in ROS-rich cancer cells for effective siRNA delivery and gene silencing. Moreover, also integrates the features and beneficial properties of both lipid and dendrimer vectors. Therefore, it represents a novel on-demand delivery system for cancer cell-specific siRNA delivery. This work opens new perspectives for designing self-assembly nanosystems for on-demand drug delivery.

摘要

小分子干扰RNA（siRNA）疗法具有高特异性、高效性和持久性等特点，在癌症和其他疾病的治疗中具有巨大潜力。然而，siRNA疗法的临床应用严重依赖于将siRNA安全且按需递送至靶细胞。在此，我们报道了一类二茂铁基两亲性树枝状大分子，用于响应癌细胞中高活性氧（ROS）含量而按需递送siRNA。这些树枝状大分子在疏水组分中带有对ROS敏感的二茂铁基团，并以带正电荷的聚（酰胺胺）树枝状支化物作为亲水性实体，具有良好的安全性和对ROS的响应特性。其中一种二茂铁基两亲性树枝状大分子在siRNA递送方面表现出色，这得益于其疏水性和亲水性的最佳平衡。其对ROS的特性有助于在富含ROS的癌细胞中特异性且高效地拆解其与siRNA的复合物，以实现有效的siRNA递送和基因沉默。此外，它还整合了脂质和树枝状大分子载体的特征及有益特性。因此，它代表了一种用于癌细胞特异性siRNA递送的新型按需递送系统。这项工作为设计用于按需药物递送的自组装纳米系统开辟了新的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b648/11280363/813d526ef75a/pharmaceutics-16-00936-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b648/11280363/3136cb7fb5d2/pharmaceutics-16-00936-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b648/11280363/9ead2ccd3cd9/pharmaceutics-16-00936-sch002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b648/11280363/c59684ebba09/pharmaceutics-16-00936-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b648/11280363/872c36fe7620/pharmaceutics-16-00936-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b648/11280363/8b5c8d45dcd6/pharmaceutics-16-00936-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b648/11280363/813d526ef75a/pharmaceutics-16-00936-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b648/11280363/3136cb7fb5d2/pharmaceutics-16-00936-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b648/11280363/9ead2ccd3cd9/pharmaceutics-16-00936-sch002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b648/11280363/c59684ebba09/pharmaceutics-16-00936-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b648/11280363/872c36fe7620/pharmaceutics-16-00936-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b648/11280363/8b5c8d45dcd6/pharmaceutics-16-00936-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b648/11280363/813d526ef75a/pharmaceutics-16-00936-g004.jpg

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