An FGFR1-Binding Peptide Modified Liposome for siRNA Delivery in Lung Cancer
Zhipeng Dong1, Yunxue Yin1, Jun Luo1
1Key Laboratory of Biomedical Functional Materials, School of Sciences, China Pharmaceutical University, Nanjing 211198, China.
Abstract:
Liposome modification by targeting ligands has been used to mediate specific interactions and drug delivery to target cells. In this study, a new peptide ligand, CP7, was found to be able to effectively bind to FGFR1 through reverse molecular docking and could cooperate with VEGFR3 to achieve targeting of A549 cells. CP7 was modified on the surface of the liposome to construct a targeted and safe nanovehicle for the delivery of a therapeutic gene, Mcl-1 siRNA. Due to the specific binding between CP7 and A549 cells, siRNA-loaded liposome-PEG-CP7 showed increased cellular uptake in vitro, resulting in significant apoptosis of tumor cells through silencing of the Mcl-1 gene, which is associated with apoptosis and angiogenesis. This gene delivery system also showed significantly better antitumor activity in tumor-bearing mice in vivo. All of these suggested that siRNA-loaded liposome-PEG-CP7 could be a promising gene drug delivery system with good bioavailability and minimal side effects for treatment.
Insights
A novel peptide ligand, CP7, facilitates targeted delivery of Mcl-1 siRNA using liposomes, enhancing cancer treatment. This targeted nanodrug delivery system effectively silenced Mcl-1, inducing tumor cell apoptosis and improving antitumor activity in vivo.
Area of Science:
- Biotechnology
- Nanomedicine
- Molecular Biology
Background:
- Liposome modification with targeting ligands enhances specific drug delivery to target cells.
- Identifying novel peptide ligands is crucial for developing targeted nanocarriers.
- Understanding gene-drug interactions is key for effective cancer therapeutics.
Purpose of the Study:
- To develop a novel targeted nanocarrier for gene delivery using a new peptide ligand, CP7.
- To evaluate the efficacy of CP7-modified liposomes for delivering Mcl-1 siRNA to A549 lung cancer cells.
- To assess the in vitro and in vivo antitumor activity of the developed gene delivery system.
Main Methods:
- Reverse molecular docking was used to identify CP7's binding affinity to FGFR1.
- CP7 was conjugated to liposomes for targeted delivery of Mcl-1 siRNA.
- In vitro cellular uptake and apoptosis assays were performed on A549 cells.
- In vivo antitumor efficacy was evaluated in tumor-bearing mice models.
Main Results:
- CP7 demonstrated effective binding to FGFR1 and cooperated with VEGFR3 for A549 cell targeting.
- siRNA-loaded liposome-PEG-CP7 exhibited enhanced cellular uptake and induced significant apoptosis in A549 cells.
- The gene delivery system showed superior antitumor activity in vivo with minimal side effects.
Conclusions:
- CP7-modified liposomes represent a promising targeted gene delivery system for cancer therapy.
- Mcl-1 siRNA delivery via liposome-PEG-CP7 effectively induces tumor cell apoptosis and inhibits tumor growth.
- This nanovehicle offers good bioavailability and reduced side effects, indicating its potential clinical application.
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