A synthetic peptide mediated active targeting of cisplatin liposomes to Tie2 expressing cells
Junhua Mai1, Shuxian Song, Mengjie Rui
1School of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, PR China.
Abstract:
Tie2 receptor is a receptor tyrosine kinase that plays important roles in vascular angiogenesis, and also highly expressed by a number of cancer cells. In this study, we reported an active targeting liposome system directed by a novel peptide ligand PH1 that can improve drug efficacies specifically to Tie2 expressing cells. The PH1 peptide (TMGFTAPRFPHY) was selected by phage display library screening combined with surface plasmon resonance binding assays. It was covalently conjugated to the distal end of DSPE-PEG(2000)-Maleimide lipid and loaded onto liposome membranes as the targeting ligand. These PH1-PEG-liposomes containing the anticancer drug cisplatin were showed to bind tightly to Tie2 positive cells, mediate active endocytosis of the drug containing liposomes, and result in much higher cell specific cytoxicities than mPEG coated liposomes. They can be used not only to target vascular endothelial cells for anti-angiogenesis effects, but also to improve drug delivery and release in Tie2 expressing cancer cells. Such liposome formulation may be developed into a very useful agent for metronomic chemotherapy.
Insights
Researchers developed a novel peptide-targeted liposome system to deliver chemotherapy drugs specifically to Tie2-expressing cancer cells, enhancing treatment efficacy and reducing side effects.
Area of Science:
- Biochemistry
- Nanotechnology
- Oncology
Background:
- The Tie2 receptor tyrosine kinase is crucial for vascular angiogenesis and is overexpressed in various cancer cells.
- Targeted drug delivery systems are needed to improve the efficacy of anticancer agents against Tie2-positive malignancies.
Purpose of the Study:
- To develop and evaluate an active targeting liposome system using a novel peptide ligand (PH1) for enhanced delivery of cisplatin to Tie2-expressing cells.
- To assess the in vitro efficacy and targeting capabilities of PH1-conjugated liposomes.
Main Methods:
- Selection of the PH1 peptide ligand through phage display and surface plasmon resonance assays.
- Covalent conjugation of PH1 peptide to DSPE-PEG(2000)-Maleimide lipids for liposome surface functionalization.
- Preparation and characterization of cisplatin-loaded PH1-PEG-liposomes.
- In vitro evaluation of liposome binding, cellular uptake, and cytotoxicity in Tie2-positive cancer cells.
Main Results:
- The PH1 peptide was successfully identified and conjugated to liposomes.
- PH1-PEG-liposomes demonstrated enhanced binding and active endocytosis by Tie2-positive cells compared to non-targeted liposomes.
- Cisplatin-loaded PH1-PEG-liposomes exhibited significantly higher specific cytotoxicity against Tie2-expressing cancer cells.
Conclusions:
- The PH1-peptide-targeted liposome system offers a promising strategy for active drug delivery to Tie2-expressing cells, including cancer cells and vascular endothelial cells.
- This targeted liposomal formulation can improve drug efficacy for anti-angiogenesis and metronomic chemotherapy, potentially leading to better therapeutic outcomes.
