Phospholipid–Block Copolymer Hybrid Vesicles with Lysosomal Escape Ability

Abstract

The success of nanoparticulate formulations in drug delivery depends on various aspects including their toxicity, internalization, and intracellular location. Vesicular assemblies consisting of phospholipids and amphiphilic block copolymers are an emerging platform, which combines the benefits from liposomes and polymersomes while overcoming their challenges. We report the synthesis of poly(cholesteryl methacrylate)- block-poly(2-(dimethylamino) ethyl methacrylate) (pCMA- b-pDMAEMA) block copolymers and their assembly with phospholipids into hybrid vesicles. Their geometry, their ζ-potential, and their ability to adsorb onto polymer-coated surfaces were assessed. Giant unilamellar vesicles were employed to confirm the presence of both the phospholipids and the block copolymer in the same membrane. Furthermore, the cytotoxicity of selected hybrid vesicles was determined in RAW 264.7 mouse macrophages, primary rat Kupffer cells, and human macrophages. The internalization and lysosomal escape ability of the hybrid vesicles were confirmed using RAW 264.7 mouse macrophages. Taken together, our findings illustrate that the reported hybrid vesicles are a promising complementary drug delivery platform for existing liposomes and polymersomes.

Biomolecule–polymer hybrid compartments: combining the best of both worlds

“…93 Compared to liposomes they also showed an enhanced lysosomal escape. 95 Instead of using lipid-polymer conjugates, both types of macromolecules eventually also form hybrid vesicles if they are just blended. The successful formation of such hybrid assemblies that bring together the biocompatibility and softness of liposomes and robustness and chemical versatility of polymersomes depends on the correct choice of the amphiphilic building blocks.…”

Interface Engineering in Multiphase Systems toward Synthetic Cells and Organelles: From Soft Matter Fundamentals to Biomedical Applications

“…Synthetic cells that can sense and respond to physical stimuli, sense and recognize chemical signals have been achieved. [364][365][366] Currently, to respond to biochemical signal by synthesizing molecules from surroundings and secreting remains challenging.…”

Hybrid giant lipid vesicles incorporating a PMMA-based copolymer

“…These hybrid vesicles have higher permeability to small dyes like carboxyfluorescein or calcein with respect to polymersomes [11][12][13] and it has been recently shown that the hybrid vesicles permeability could be increased by adding phospholipase A2 that can selectively degrade lipids [14]. Examples of hybrid nanoscale polymersomes have been proposed for applications in nanomedicine and seemed to improve the targeting efficiency [15,16]. Interestingly, hybrid vesicles at the micron scale are valid alternatives to giant liposomes as simplified cell models for a deeper understanding of fundamental biological processes [17,18].…”

“…Zong et al [16] to confirm the presence of both phospholipids and the block copolymer in the same membrane, pCMA constitutes the hydrophobic block, while the pH-sensitive pDMAEMA constitutes the hydrophilic block. These GUVs were electroformed and the maximum polymer content was 70% w/w (corresponding to 3.6 mol % using Mn=47.5 kD as reported in Table of the cited work).…”

“…Also, hybrid nano-vesicles were formed by this copolymer mixed with phospholipids containing palmitoyl and oleyl as fatty acyl groups and different charged headgroups (i.e. phosphatidylcholine, ethylphosphocholine and phosphatidylserine) showed a prevalent cytosolic localization when incubated with mouse macrophages, indicating a good potential for applications in drug delivery [16].…”