Nanoparticles (NPs) are being used extensively for tumor drug delivery. These devices offer the advantage of their size, protection of the encapsulated species, and biodegradability to prevent accumulation in the interstitium. Our laboratory has synthesized polylactide fumarate (PLAF, PLGF) macromers capable of self-assembling into biodegradable and biocompatible NPs with average particle size of 280 nm. To assess the possibility of further decreasing the particle size and distribution of PLGF NPs, the polymers were conjugated with the peptide sequence Cys-Val-Val-Val-Val-Val-Val-Lys-Lys (CV6K2), which is known to self-assemble in aqueous solution into vesicles of about 50-60 nm in size. The results indicate that the PLGF-CV6K2 conjugates are capable of self-assembling into NPs of 100 nm in diameter. The NPs are proposed as having a bilayer structure, with peptide chains facing the aqueous environment and the polymer chains compacted in an internal hydrophobic layer. Degradation kinetics and release profiles show that the NPs could effectively retain and release Paclitaxel up to 30 days until completely degraded. The NPs act as reservoirs for sustained release of the active agent by diffusion and degradation of the matrix when taken up by tumor cells.