Premium
A Novel Self‐Assembled Mitochondria‐Targeting Protein Nanoparticle Acting as Theranostic Platform for Cancer
Author(s) -
Zhu XinJie,
Li RiFei,
Xu Liang,
Yin Hui,
Chen Long,
Yuan Ye,
Zhong Wu,
Lin Jian
Publication year - 2019
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.201803428
Subject(s) - paclitaxel , in vivo , biocompatibility , mitochondrion , cancer cell , nanoparticle , in vitro , chemistry , reactive oxygen species , nanomedicine , biophysics , nanotechnology , materials science , cancer , biochemistry , biology , genetics , microbiology and biotechnology , organic chemistry
Self‐assembled protein nanoparticles have attracted much attention in biomedicine because of their biocompatibility and biodegradability. Protein nanoparticles have become widely utilized as diagnostic or therapeutic agents for various cancers. However, there are no reports that protein nanoparticles can specifically target mitochondria. This targeting is desirable, since mitochondria are critical in the development of cancer cells. In this study, the discovery of a novel self‐assembled metal protein nanoparticle, designated GST‐MT‐3, is reported, which targets the mitochondria of cancer cells within 30 min in vitro and rapidly accumulates in tumors within 1 h in vivo. The nanoparticles chelate cobalt ions [GST‐MT‐3(Co 2+ )], which induces reactive oxygen species (ROS) production and reduces the mitochondrial membrane potential. These effects lead to antitumor activity in vivo. GST‐MT‐3(Co 2+ ) with covalently conjugated paclitaxel synergistically suppress tumors and prolong survival. Importantly, the effective dosage of paclitaxel is 50‐fold lower than that utilized in standard chemotherapy (0.2 vs 10 mg kg −1 ). To the best of the authors' knowledge, GST‐MT‐3 is the first reported protein nanoparticle that targets mitochondria. It has the potential to be an excellent platform for combination therapies.