Dual-Targeted Cascade-Responsive Prodrug Micelle System
for Tumor Therapy in Vivo
Posted on 2017-08-11 - 17:51
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-p-(4-trimethylammonium)butoxyphenyl)-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 in vitro and in vivo 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.
CITE THIS COLLECTION
DataCite
3 Biotech
3D Printing in Medicine
3D Research
3D-Printed Materials and Systems
4OR
AAPG Bulletin
AAPS Open
AAPS PharmSciTech
Abhandlungen aus dem Mathematischen Seminar der Universität Hamburg
ABI Technik (German)
Academic Medicine
Academic Pediatrics
Academic Psychiatry
Academic Questions
Academy of Management Discoveries
Academy of Management Journal
Academy of Management Learning and Education
Academy of Management Perspectives
Academy of Management Proceedings
Academy of Management Review
Dai, Liangliang; Cai, Ruisi; Li, Menghuan; Luo, Zhong; Yu, Yonglin; Chen, Weizhen; et al. (2017). Dual-Targeted Cascade-Responsive Prodrug Micelle System
for Tumor Therapy in Vivo. ACS Publications. Collection. https://doi.org/10.1021/acs.chemmater.7b02513
or
Select your citation style and then place your mouse over the citation text to select it.
SHARE
Usage metrics
Read the peer-reviewed publication
AUTHORS (10)
LD
Liangliang Dai
RC
Ruisi Cai
ML
Menghuan Li
ZL
Zhong Luo
YY
Yonglin Yu
WC
Weizhen Chen
XS
Xinkun Shen
YP
Yuxia Pei
XZ
Xiaojing Zhao
KC
Kaiyong Cai
KEYWORDS
polymer micellesTumor Therapyfirst-stage destabilizationcationic porphyrinGSHCPTstudy reportsdelivery efficiencyside effectsactivates mitochondria apoptotic pathwaylight irradiationmitochondria-targeting photosensitizerantitumor drugstumor siteendoPDEA blocktumor cellsprodrug micellessubcellular levelsvivo studiesmicellar nanosystemmicellar drug delivery systemcombinational antitumor efficacymitochondria-targeted tumor therapycytoplasmantitumor efficacyfolate receptor-mediated pathwayDual-Targeted Cascade-Responsive Prodrug Micelle Systemlaser irradiationMTPPROS generationBOH block