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Anionic Polymerization of an Amphiphilic Copolymer for Preparation of Block Copolymer Micelles Stabilized by π-π Stacking Interactions
Published on: October 10, 2016
Light scattering evidence of selective protein fouling on biocompatible block copolymer micelles
Fernando C Giacomelli1, Petr Stepánek, Vanessa Schmidt
1Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, 09210-170 Santo André, Brazil. fernando.giacomelli@ufabc.edu.br
Abstract:
Selective protein fouling on block copolymer micelles with well-known potential for tumour-targeting drug delivery was evidenced by using dynamic light scattering measurements. The stability and interaction of block copolymer micelles with model proteins (BSA, IgG, lysozyme and CytC) is reported for systems featuring a hydrophobic (poly[2-(diisopropylamino)-ethyl methacrylate]) (PDPA) core and hydrophilic coronas comprising poly(ethylene oxide)/poly(glycerol monomethacrylate) (PEO-b-PG2MA) or poly[2-(methacryloyloxy)ethyl phosphorylcholine] (PMPC). The results revealed that protein size and hydrophilic chain density play important roles in the observed interactions. The PEO(113)-b-PG2MA(30)-b-PDPA(50) nanoparticles are stable and protein adsorption is prevented at all investigated protein environments. The successful protein-repellent characteristic of these nanoparticles is attributed to a high hydrophilic surface chain density (>0.1 chains per nm(2)) and to the length of the hydrophilic chains. On the other hand, although PMPC also has protein-repellent characteristics, the low surface chain density of the hydrophilic shell is supposed to enable interactions with small proteins. The PMPC(40)-b-PDPA(70) micelles are stable in BSA and IgG environments due to weak repulsion forces between PMPC and the proteins, to the hydration layer, and particularly to a size-effect where the large BSA (R(H) = 4.2 nm) and IgG (R(H) = 7.0 nm) do not easily diffuse within the PMPC shell. Conversely, a clear interaction was observed with the 2.1 nm radius lysozyme. The lysozyme protein can diffuse within the PMPC micellar shell towards the PDPA hydrophobic core in a process favored by its smaller size and the low hydrophilic PMPC surface chain density (∼0.049 chains per nm(2)) as compared to PEO-b-PG2MA (∼0.110 chains per nm(2)). The same behavior was not evidenced with the 2.3 nm radius positively charged CytC, probably due to its higher surface hydrophilicity and the consequent chemical incompatibility with PDPA.
Insights
Block copolymer micelles show potential for drug delivery. High hydrophilic chain density prevents protein adsorption, while lower density allows interaction with smaller proteins, impacting nanoparticle stability and drug delivery applications.
Area of Science:
- Materials Science
- Biomedical Engineering
- Nanotechnology
Background:
- Block copolymer micelles are investigated for their potential in targeted drug delivery, particularly for tumors.
- Understanding protein-micelle interactions is crucial for ensuring the stability and efficacy of nanocarriers in biological environments.
- Selective protein fouling can affect the performance of drug delivery systems.
Purpose of the Study:
- To investigate the stability and protein interaction of block copolymer micelles with varying hydrophilic corona compositions.
- To determine the influence of protein size and hydrophilic chain density on protein fouling.
- To evaluate the potential of these micelles as protein-repellent nanocarriers for drug delivery.
Main Methods:
- Dynamic light scattering (DLS) measurements were employed to assess micelle stability and protein interactions.
- Model proteins including Bovine Serum Albumin (BSA), Immunoglobulin G (IgG), lysozyme, and Cytochrome C (CytC) were used.
- Block copolymer micelles with poly[2-(diisopropylamino)-ethyl methacrylate] (PDPA) hydrophobic cores and PEO-b-PG2MA or PMPC hydrophilic coronas were synthesized and studied.
Main Results:
- Poly(ethylene oxide)/poly(glycerol monomethacrylate) (PEO-b-PG2MA) micelles exhibited excellent protein repellency due to high hydrophilic chain density (>0.1 chains/nm²) and chain length.
- Poly[2-(methacryloyloxy)ethyl phosphorylcholine] (PMPC) micelles showed interactions with smaller proteins like lysozyme, attributed to lower surface chain density (∼0.049 chains/nm²) and protein size.
- BSA and IgG did not significantly interact with PMPC micelles due to repulsion, hydration layers, and size exclusion, while lysozyme diffused into the micellar shell.
Conclusions:
- Hydrophilic chain density and length are critical factors determining protein fouling on block copolymer micelles.
- PEO-b-PG2MA based micelles demonstrate superior protein-repellent properties, making them promising for drug delivery applications.
- PMPC micelles show selective protein interactions, suggesting potential for specific targeting or controlled release mechanisms.
