Efficient Click Synthesis of a Protonized and Reduction-Sensitive Amphiphilic Small-Molecule Prodrug Containing Camptothecin and Gemcitabine for a Drug Self-Delivery System.
Animals
Antineoplastic Agents
/ chemistry
Camptothecin
/ analogs & derivatives
Cell Survival
/ drug effects
Click Chemistry
/ methods
Deoxycytidine
/ analogs & derivatives
Drug Delivery Systems
/ methods
Drug Liberation
Drug Stability
Half-Life
Hep G2 Cells
Humans
Hydrogen-Ion Concentration
Hydrophobic and Hydrophilic Interactions
Male
Nanoparticles
/ chemistry
Prodrugs
/ chemistry
Rats
Rats, Sprague-Dawley
Tissue Distribution
Triazoles
/ chemistry
Gemcitabine
cancer therapy
drug self-delivery systems
drug−drug conjugate
nanomedicine
small-molecule prodrug
Journal
Molecular pharmaceutics
ISSN: 1543-8392
Titre abrégé: Mol Pharm
Pays: United States
ID NLM: 101197791
Informations de publication
Date de publication:
03 09 2019
03 09 2019
Historique:
pubmed:
28
7
2019
medline:
9
6
2020
entrez:
27
7
2019
Statut:
ppublish
Résumé
Drug self-delivery systems consisting of small-molecule active drugs with nanoscale features for intracellular delivery without the need for additional polymeric carriers have drawn much attention recently. In this work, we proposed a highly efficient strategy to fabricate protonized and reduction-responsive self-assembled drug nanoparticles from an amphiphilic small-molecule camptothecin-ss-1,2,3-triazole-gemcitabine conjugate (abbreviated as CPT-ss-triazole-GEM) for combination chemotherapy, which was prepared via a Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) "click" reaction. To obtain this drug-triazole-drug conjugate, we first prepared a CPT derivate containing a propargyl group linked with a disulfide group and a GEM derivate attached to an azide group. Subsequently, the two kinds of modified drugs were connected together through a CuAAC reaction between the alkynyl and azide groups to yield the CPT-ss-triazole-GEM prodrug. The characterizations of chemical structures of these intermediates and the final product were performed by
Identifiants
pubmed: 31348660
doi: 10.1021/acs.molpharmaceut.9b00349
doi:
Substances chimiques
Antineoplastic Agents
0
Prodrugs
0
Triazoles
0
Deoxycytidine
0W860991D6
Camptothecin
XT3Z54Z28A
Gemcitabine
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM