Smart Nanotransformers with Unique Enzyme-Inducible Structural Changes and Drug Release Properties. Academic Article uri icon

Overview

abstract

  • We previously reported a high aspect ratio peptide nanofiber that could be effectively delivered to tumors with minimal nonspecific uptake by other organs. The peptidic nature offers the design flexibility of smart formulation with unique responsiveness. Two new formulations that behave congruously as nanotransformers (NTFs) are reported herein. NTF1 and NTF2 could biomechanically remodel upon enzyme activation to generate a degradable and an aggregable effect, respectively, within the lysosomal compartment. These NTFs were further evaluated as carriers of mertansine (DM1), a microtubule inhibitor. DM1-loaded NTF1 could be degraded by cathepsin B (CathB) to release the same active metabolite, as previously described in the lysosomal degradation of antibody-DM1 conjugate. In contrast, CathB only partially digested DM1-loaded NTF2 and induced aggregate formation to become a storage reservoir with slow payload release property. The DM1-loaded NTF1 exhibited a comparable cytotoxicity to the free drug and was more effective than the NTF2 formulation in eradicating triple negative breast cancer. Our data suggested that biological transformers with distinct enzyme-induced structural changes and payload release profiles could be designed for the intracellular delivery of cytotoxic and imaging agents.

publication date

  • May 24, 2016

Research

keywords

  • Cathepsin B
  • Drug Carriers
  • Maytansine
  • Nanofibers
  • Oligopeptides
  • Tubulin Modulators

Identity

PubMed Central ID

  • PMC5594411

Scopus Document Identifier

  • 84974846207

Digital Object Identifier (DOI)

  • 10.1021/acs.biomac.6b00227

PubMed ID

  • 27180972

Additional Document Info

volume

  • 17

issue

  • 6