Fabrication of nanoparticles from a synthesized peptide amphiphile as a versatile therapeutic cargo for high antiproliferative activity in tumor cells

Abstract

Nanoparticles with encapsulated small molecules have attained vital importance in anticancer research. Peptide-based nanoparticles show their versatility in drug delivery due to their excellent biocompatibility and nontoxic nature. We demonstrate here the design and fabrication of peptide-based nanoparticles as dual-therapeutic cargo for the controlled release of hydrophilic 5-Fluorouracil (5Fu) and hydrophobic camptothecin (CPT), simultaneously. The covalent conjugation of 5Fu with the peptide, through a stimuli-responsive linker, provided better control over the release of 5Fu and dramatically reduced the possibility of leaching of the small molecule. As anticipated, the peptide-5Fu nanoparticles were efficient to encapsulate a second chemotherapeutic molecule CPT in its hydrophobic region. The stimuli-responsive release of 5Fu was carefully monitored by HPLC, NMR, and UV-visible spectroscopy. On the other hand, the release of the hydrophobic drug CPT from the nanoparticles was determined to be in a diffusion-controlled fashion. Assessment of performance in human cervical HeLa cell lines demonstrated the peptide-drug nanoparticles to be highly nontoxic. Whereas, the simultaneous release of the two antitumor agents, in a controlled manner, resulting in rapid antiproliferation of the tumor cells.

Keywords: 5-Fluorouracil; Camptothecin; Drug conjugate; Dual delivery; Nanoparticles; Peptides; Photo-responsive; Self-assembly.