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Phospholipid-Block Copolymer Hybrid Vesicles with Lysosomal Escape Ability
Wei Zong1,2, Bo Thingholm2, Fabian Itel2
1State Key Laboratory of Urban Water Resource and Environment, School of Chemistry and Chemical Engineering , Harbin Institute of Technology , 92 West Da-Zhi Street , Harbin 150001 , China.
Langmuir : the ACS Journal of Surfaces and Colloids
|May 20, 2018
Summary
New hybrid vesicles combining phospholipids and block copolymers show promise for drug delivery. These novel nanoparticles demonstrate low toxicity and effective cellular uptake and escape, offering a new platform for advanced therapies.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Drug Delivery Systems
Background:
- Nanoparticulate formulation success hinges on toxicity, cellular internalization, and intracellular fate.
- Liposomes and polymersomes are established drug delivery platforms with inherent limitations.
- Hybrid vesicles offer a potential solution by integrating the advantages of both liposomes and polymersomes.
Purpose of the Study:
- To synthesize and characterize novel hybrid vesicles composed of phospholipids and poly(cholesteryl methacrylate)- block-poly(2-(dimethylamino) ethyl methacrylate) (pCMA-b-pDMAEMA) block copolymers.
- To evaluate the physicochemical properties, cytotoxicity, cellular internalization, and lysosomal escape of these hybrid vesicles.
- To assess the potential of these hybrid vesicles as a complementary drug delivery platform.
Main Methods:
- Synthesis of pCMA-b-pDMAEMA block copolymers and their assembly with phospholipids into hybrid vesicles.
- Characterization of vesicle geometry, ζ-potential, and surface adsorption properties.
- Cytotoxicity assessment in RAW 264.7 mouse macrophages, primary rat Kupffer cells, and human macrophages.
- Evaluation of cellular internalization and lysosomal escape using fluorescence microscopy in RAW 264.7 cells.
Main Results:
- Successful synthesis and assembly of hybrid vesicles confirmed by giant unilamellar vesicle experiments.
- Hybrid vesicles exhibited favorable physicochemical properties and low cytotoxicity across tested macrophage models.
- Demonstrated efficient cellular internalization and significant lysosomal escape capabilities in macrophages.
Conclusions:
- The developed hybrid vesicles represent a promising advancement in nanoparticulate drug delivery.
- These hybrid vesicles offer a versatile platform that complements existing liposomal and polymer-based systems.
- The findings support the potential application of these novel vesicles in targeted and effective therapeutic strategies.
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