In this work, we prepared a novel
cancer chemotherapeutic nanocarrier through the self-assembly of a mussel-derived,
cancer-targeting
peptide with a pH-sensitive conjugation of
antitumor drugs. The biomimetic
peptide was designed with a fluorescent molecule
fluorescein isothiocyanate for imaging, a RGD sequence for
cancer-targeting and tetravalent
catechol groups for dynamic conjugation of the
antitumor drug bortezomib via pH-cleavable
boronic acid-
catechol esters. Our study demonstrated that the
peptide-based
prodrug nanocarrier dramatically the enhanced specific cellular uptake and cytotoxicity toward human
breast cancer cells in vitro in comparison with free
drug and nontargeting control nanoparticles. Likewise, the
prodrug nanocarrier showed improved therapeutic efficacy and low systematic toxicity in vivo. Considering highly biomimetic nature of the
peptide-based nanocarriers, rapid drug release from the dynamically conjugated
prodrugs, and convenience of introducing
cancer-targeting activity onto this nanosystem, we believe our work would provide new ideas for the development of intelligent and biocompatible drug delivery systems to improve the
chemotherapy efficacy in clinic. Furthermore, the pH-sensitive
drug conjugation mechanism on
peptide-based nanocarriers would provide a hint for the exploitation of dynamic
prodrug strategies and the development of highly biocompatible nanocarriers using biogenic materials, e.g., the proteinogenic nanomaterials decorated with drugs through dynamic covalent chemistry.