Melt polycondensation approach is developed for new classes of reduction responsive disulfide containing functional polyesters based on L-cystine amino acid resources under solvent free process. L-Cystine was converted into multi-functional ester-urethane monomer and subjected to thermoselective transesterification at 120 degrees C with commercial diols in the presence of Ti(OBu)(4) to produce polyesters with urethane side chains. The polymers were produced in moderate to high molecular weights and the polymers were found to be thermally stable up to 250 degrees C. The beta-sheet hydrogen bonding interaction among the side chain urethane unit facilitated the self-assembly of the polyester into amyloid-like fibrils. The deprotection of urethane unit into amine functionality modified the polymers into water soluble cationic polyester spherical nano-particles. The reduction degradation of disulfide bond was studied using DTT as a reducing agent and the high molecular weight polymers chains were found be chopped into low molecular weight oligomers. The cytotoxicity of cationic disulfide nanoparticle was studied in MCF-7 cells and they were found to be biocompatible and non-toxic to cells upto 50 mu g/mL. The custom designed reduction degradable and highly biocompatible disulfide polyesters from L-cystine are useful for futuristic biomedical applications. (C) 2016 Wiley Periodicals, Inc.