10.1021/acs.chemmater.7b02513.s001
Liangliang Dai
Liangliang
Dai
Ruisi Cai
Ruisi
Cai
Menghuan Li
Menghuan
Li
Zhong Luo
Zhong
Luo
Yonglin Yu
Yonglin
Yu
Weizhen Chen
Weizhen
Chen
Xinkun Shen
Xinkun
Shen
Yuxia Pei
Yuxia
Pei
Xiaojing Zhao
Xiaojing
Zhao
Kaiyong Cai
Kaiyong
Cai
Dual-Targeted Cascade-Responsive Prodrug Micelle System
for Tumor Therapy <i>in Vivo</i>
American Chemical Society
2017
polymer micelles
Tumor Therapy
first-stage destabilization
cationic porphyrin
GSH
CPT
study reports
delivery efficiency
side effects
activates mitochondria apoptotic pathway
light irradiation
mitochondria-targeting photosensitizer
antitumor drugs
tumor site
endo
PDEA block
tumor cells
prodrug micelles
subcellular levels
vivo studies
micellar nanosystem
micellar drug delivery system
combinational antitumor efficacy
mitochondria-targeted tumor therapy
cytoplasm
antitumor efficacy
folate receptor-mediated pathway
Dual-Targeted Cascade-Responsive Prodrug Micelle System
laser irradiation
MTPP
ROS generation
BOH block
2017-08-11 17:51:25
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Dual-Targeted_Cascade-Responsive_Prodrug_Micelle_System_for_Tumor_Therapy_i_in_Vivo_i_/5305330
This
study reports a cascade-responsive disassemble micellar drug
delivery system with dual-targeting potential (cell and mitochondria
targeting), which optimizes the distribution of antitumor drugs on
systemic, local, and subcellular levels to enhance antitumor efficacy.
A new cationic porphyrin derivative 5-(3-hydroxy-<i>p</i>-(4-trimethylammonium)Âbutoxyphenyl)-10,15,20-triphenylporphyrin chlorine
(MTPP) is synthesized as a mitochondria-targeting photosensitizer.
After accumulating at a tumor site, the micellar nanosystem is endocytosed
by tumor cells facilitated by the folate receptor-mediated pathway.
Then, the hydrophobic PDEA block would be protonated in intracellular
acidic endo-/lysosomes and promote the escape of prodrug micelles
from endo-/lysosome to cytoplasm, resulting in the first-stage destabilization
of micelles. Subsequently, the CPT is released in response to high
concentration of GSH in cytoplasm, which would greatly increase the
hydrophilicity of the BOH block and initiate the complete disassembly
of the polymer micelles owing to the damage of the hydrophilic–hydrophobic
balance. Additionally, the released MTPP is selectively accumulated
in mitochondria and activates mitochondria apoptotic pathway upon
light irradiation as a result of ROS generation. Both <i>in vitro</i> and <i>in vivo</i> studies indicate that the polymeric
micelle not only effectively improves the targeted delivery efficiency
but also dramatically enhances the combinational antitumor efficacy
while reducing the side effects associated with the laser irradiation
and mitochondria-targeted tumor therapy.