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Published on: May 2, 2019
ROS-Responsive Ferrocenyl Amphiphilic PAMAM Dendrimers for On-Demand Delivery of siRNA Therapeutics to Cancer Cells
Peng Chen1, Zhihui Wang1, Xinmo Wang1
1Center of Advanced Pharmaceuticals and Biomaterials, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China.
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 (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-C, 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-C 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.
Insights
Researchers developed novel ferrocenyl amphiphilic dendrimers for targeted siRNA delivery. These dendrimers respond to high ROS in cancer cells, enabling efficient gene silencing and on-demand drug release.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Drug Delivery Systems
Background:
- Small interfering RNA (siRNA) therapeutics offer high specificity and potency for treating diseases.
- Effective clinical implementation of siRNA relies on safe and on-demand delivery to target cells.
- Current delivery systems face challenges in achieving targeted and responsive release.
Purpose of the Study:
- To develop a novel class of ferrocenyl amphiphilic dendrimers (Fc-AmDs) for on-demand siRNA delivery.
- To engineer dendrimers that are responsive to the high reactive oxygen species (ROS) content characteristic of cancer cells.
- To create a safe and efficient delivery system for cancer-specific siRNA therapeutics.
Main Methods:
- Synthesis of a family of ferrocenyl amphiphilic dendrimers (Fc-AmDs) with ROS-sensitive ferrocene moieties and poly(amidoamine) dendrons.
- Evaluation of Fc-AmDs for their safety profiles and ROS-responsive properties.
- Assessment of Fc-C, a specific Fc-AmD, for its efficacy in siRNA delivery, complex disassembly, and gene silencing in cancer cells.
Main Results:
- Ferrocenyl amphiphilic dendrimers (Fc-AmDs) were successfully synthesized, exhibiting ROS-responsive properties and favorable safety profiles.
- The dendrimer Fc-C demonstrated superior siRNA delivery capabilities due to an optimal balance of hydrophobicity and hydrophilicity.
- Fc-C facilitated specific and efficient disassembly of siRNA complexes within ROS-rich cancer cells, leading to effective gene silencing.
Conclusions:
- Fc-C represents a novel, on-demand delivery system for cancer cell-specific siRNA delivery, integrating properties of lipid and dendrimer vectors.
- The ROS-responsive nature of Fc-C enables targeted siRNA release and gene silencing in the tumor microenvironment.
- This study opens new avenues for designing self-assembly nanosystems for on-demand drug delivery applications.
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