Preparation of biodegradable peptide nanospheres with hetero PEG brush surfaces

Controlled hetero poly(ethylene glycol) (PEG) brushes composed of higher and lower molecular weight PEG chains are for the first time prepared onto biodegradable peptide nanospheres. Hence, the PEG chains are easily detached and re-attached based on the thiol-disulfide chemistry of the interfacial disulfide bonds of PEG-SS-peptide nanospheres. The density of the 1(st) PEG with a molecular weight of 2000 (M¯w = 2k) is controlled by altering the reduction conditions. Subsequently, 2(nd) PEG chains with a higher M¯w (from 5000 to 20 000) are constructed by oxidative reactions. Hetero PEG2k 60%/PEG5k 40% demonstrates about 2.5-fold greater protein resistance than homo PEG2k 100% or PEG5k 40%, and exceptional dispersion stability in serum for over three weeks. Hetero PEG brush peptide nanospheres will be useful as bioinert drug carriers for biomedical applications.