Title | Smart Nanotransformers with Unique Enzyme-Inducible Structural Changes and Drug Release Properties. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Bellat V, Lee HHee, Vahdat L, Law B |
Journal | Biomacromolecules |
Volume | 17 |
Issue | 6 |
Pagination | 2040-9 |
Date Published | 2016 06 13 |
ISSN | 1526-4602 |
Keywords | Breast Neoplasms, Cathepsin B, Cell Culture Techniques, Cell Line, Tumor, Cell Survival, Drug Carriers, Drug Liberation, Female, Humans, Maytansine, Microscopy, Fluorescence, Nanofibers, Oligopeptides, Tubulin Modulators |
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. |
DOI | 10.1021/acs.biomac.6b00227 |
Alternate Journal | Biomacromolecules |
PubMed ID | 27180972 |
PubMed Central ID | PMC5594411 |
Grant List | UL1 TR000457 / TR / NCATS NIH HHS / United States |
Related Institute:
Molecular Imaging Innovations Institute (MI3)