Light scattering evidence of selective protein fouling on biocompatible block copolymer micelles.
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.
Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, 09210-170 Santo André, Brazil. fernando.giacomelli@ufabc.edu.br
Fernando C
FC
Giacomelli
Petr
P
Stepánek
Vanessa
V
Schmidt
Eliézer
E
Jäger
Alessandro
A
Jäger
Cristiano
C
Giacomelli
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D002417:Cattle; D045304:Cytochromes c / Q000737:chemistry / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008027:Light; D008823:Micelles; D009113:Muramidase / Q000737:chemistry / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D011109:Polymethacrylic Acids / Q000737:chemistry; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D012542:Scattering, Radiation; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000378:metabolism
D001672:Biocompatible Materials; D008823:Micelles; D011108:Polymers; D011109:Polymethacrylic Acids; D011506:Proteins; C511861:poly(2-(diisopropylamino)ethyl methacrylate); D012710:Serum Albumin, Bovine; D045304:Cytochromes c; D009113:Muramidase