A Nanosystem of Amphiphilic Oligopeptide-Drug Conjugate Actualizing Both αvβ3 Targeting and Reduction-Triggered Release for Maytansinoid.

ABSTRACT: To design a prodrug-based self-assembling nanosystem with both ligand targeting and stimuli-responsive features, and elucidate the superiority of each targeting strategy and the synergistic effect between them, we synthesized four small molecule amphiphilic peptide-drug conjugates (APDCs) using maytansinoid (DM1) as a cytotoxic agent, cRGDfK as a homing peptide, and disulfide (SS) or thioether (SMCC) as linker. Owing to their amphiphilicity, the APDCs could self-assemble into nanoparticles (APDC@NPs) which were evaluated in vitro in three different cell lines and in vivo in tumor-bearing C57BL/6 mice. The RSSD@NPs showed the strongest interaction with αvβ3 integrin, highest cell uptake and intracellular free drug level, and best antitumor efficacy in vitro and in vi

SUBMITTER: Liang Y 

PROVIDER: S-EPMC5595133 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature