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

被引：4

作者：

Chen, Peng ^{[1
]}

Wang, Zhihui ^{[1
]}

Wang, Xinmo ^{[1
]}

Gong, Junni ^{[1
]}

Sheng, Ju ^{[1
]}

Pan, Yufei ^{[1
]}

Zhu, Dandan ^{[1
]}

Liu, Xiaoxuan ^{[1
]}

机构：

[1] China Pharmaceut Univ, Ctr Adv Pharmaceut & Biomat, State Key Lab Nat Med, Nanjing 211198, Peoples R China

来源：

PHARMACEUTICS | 2024年 / 16卷 / 07期

基金：

中国国家自然科学基金;

关键词：

amphiphilic dendrimer; ROS responsive; siRNA therapeutics; siRNA delivery; SMALL INTERFERING RNA; POTENT;

D O I：

10.3390/pharmaceutics16070936

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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 (Fc-AmDs) 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, Fc-C8-AmD 8A, 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, Fc-C8-AmD 8A 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.

引用

页数：16

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