Self-assembling Dextran prodrug for redox- and pH-responsive co-delivery of therapeutics in cancer cells

被引：28

作者：

Curcio, Manuela ^{[1
]}

Cirillo, Giuseppe ^{[1
]}

Paoli, Alessandro ^{[1
]}

Naimo, Giuseppina Daniela ^{[1
]}

Mauro, Loredana ^{[1
]}

Amantea, Diana ^{[1
]}

Leggio, Antonella ^{[1
]}

Nicoletta, Fiore Pasquale ^{[1
]}

Lemma, Francesca ^{[1
]}

机构：

[1] Univ Calabria, Dept Pharm & Hlth & Nutr Sci, I-87036 Arcavacata Di Rende, CS, Italy

来源：

COLLOIDS AND SURFACES B-BIOINTERFACES | 2020年 / 185卷

关键词：

Self-assembling prodrugs; Dextran derivative; Stimuli-responsive carrier; Anticancer activity; DOXORUBICIN; NANOPARTICLES; MICELLES; RELEASE; ACID; POLYMERSOMES; LIPOSOMES; VERSATILE;

D O I：

10.1016/j.colsurfb.2019.110537

中图分类号：

Q6 [生物物理学];

学科分类号：

071011 ;

摘要：

Self-assembling prodrug containing pH- and redox-responsive functional groups was prepared by covalent conjugation of Doxorubicin (Dox) and lipoic acid (LA) to a polyaldehyde Dextran (PAD). The resultant amphiphilic DoxPADLA forms, in a single step, hemocompatible vesicular systems able to respond to intracellular signals without using external crosslinking agents. Camptothecin (CPT) was encapsulated exploiting the hydrophobic interactions with the vesicle membrane, and release experiments, carried out in media mimicking the physiological and endolysosomial compartments, in the absence or presence of Glutathione, proved the ability of the system to modulate drug release in relation to the variation of pH and redox potential. Cytotoxicity assays and confocal experiments demonstrated the efficacy of the vesicle formulation in enhancing the synergistic anticancer effect of the delivered Dox and CPT and a rapid and significant internalization of the carrier in cancer cells.

引用

页数：8

共 52 条

[21] Biodegradable amphiphilic block copolymers bearing protected hydroxyl groups: Synthesis and characterization [J].