Phospholipid—polymer amphiphile hybrid assemblies and their interaction with macrophages

Abstract

Recently, the combination of lipids and block copolymers has become an alternative to liposomes and polymersomes as nano-sized drug carriers. We synthesize novel block copolymers consisting of poly(cholesteryl acrylate) as the hydrophobic core and poly(N-isopropylacrylamide) (PNIPAAm) as the hydrophilic extensions. Their successful phospholipid-assisted assembly into vesicles is demonstrated using the evaporation-hydration method. The preserved thermo-responsive property of the lipid-polymer hybrids is shown by a temperature dependent adsorption behaviour of the vesicles to poly(l lysine) coated surfaces. As expected, the vesicle adsorption is found to be higher at elevated temperatures. The cellular uptake efficiency of hybrids is assessed using macrophages with applied shear stress. The amount of adhering macrophages is affected by the time and level of applied shear stress. Further, it is found that shorter PNIPAAm extensions lead to higher uptake of the assemblies by the macrophages with applied shear stress. No inherent cytotoxicity is observed at the tested conditions. Taken together, this first example of responsive lipid-polymer hybrids, and their positive biological evaluation makes them promising nano-sized drug carrier candidates.

Subcompartmentalized Nanoreactors as Artificial Organelle with Intracellular Activity

“…Applied Shear Stress : Assessing the interaction of drug carriers and cells, using predominantly endothelial cells, with applied shear stress starts to be recognized as an important factor as recently reviewed by Godoy‐Gallardo et al Endothelial cells line our blood vessel and are therefore permanently exposed to blood flow. Furthermore, circulating macrophages experience the same mechanical forces, and its relevance has recently been reported by us and others . Since every potential artificial organelle administered intravenously will be exposed to the blood stream and the induced mechanical forces such as shear stress, the uptake of P PDA , P PEG , and P RGD by endothelial cells, and macrophages were reassessed with applied shear stress ( τ 4 = 4 dyn cm −2 ) using a commercial microfluidic setup.…”

The combination of block copolymers and phospholipids to form giant hybrid unilamellar vesicles (GHUVs) does not systematically lead to “intermediate” membrane properties

“…In this still restricted but emerging field of hybrid vesicles/membranes, so far diblock copolymers were most often used, but interest on triblock copolymer architecture is growing. 15 In this context, it is important that the exact role of copolymer architecture on membrane structuration and properties is deciphered, both at the micro and nanoscale. Further studies on GHUVs and LHUVs using diblock copolymers with same chemical nature (PDMS and PEO) are under way.…”

“…2,3 A significant number of studies have focused on their use in different fields, such as drug delivery [4][5][6][7] , drug targeting, 8 nanoreactors, 7,9,10 biomolecular recognition and interaction with nanoparticles [11][12][13][14] , or their interaction with biological media. 15 So far, only a relatively moderate part of the work published on the subject has focused on the selfassembly problematic: how can we modulate the phase separation process during the self-assembly, preventing formation of separated liposomes and polymersomes, and obtain membranes with lipid domains of controlled size? The relation-ship between membrane composition (% polymer lipid, presence of domains) and properties like elasticity, permeability, tumor-targeting ability, is not clearly established so far, especially at the nanoscale in Large Hybrid Unilamellar Vesicles, LHUV, often used in the above mentioned studies.…”

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

“…Phospholipidblock copolymer conjugates were used for the preparation of hybrid vesicles that were particularly studied for their cellular interactions. 93,94 They demonstrated the relevance of shear stress in cell uptake and how shorter hydrophobic extensions are enhancing their internalization by macrophages. 93 Compared to liposomes they also showed an enhanced lysosomal escape.…”