Details

Autor(en) / Beteiligte

• Jin, Rong
• Guo, Xuelian
• Dong, Lingli
• Xie, Enyuan
• Cao, Aoneng

Titel

Amphipathic dextran-doxorubicin prodrug micelles for solid tumor therapy

Ist Teil von

• Colloids and surfaces, B, Biointerfaces, 2017-10, Vol.158, p.47-56

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2017

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• [Display omitted] Self-assembly behavior of Dex-DCA-DOX prodrugs and their micelles for pH-triggered intracellular DOX delivery. •A series of dextran-based prodrugs (denoted as Dex-DCA-DOX) were designed.•The Dex-DCA-DOX prodrugs can self-assemble to form nanosized micelles.•These Dex-DCA-DOX prodrug micelles showed pH-triggered DOX release.•These micelles exhibited improved anti-cancer efficacy but low systemic toxicity. A group of micelles self-assembled from deoxycholic acid-doxorubicin-conjugated dextran (denoted as Dex-DCA-DOX) prodrugs were designed and prepared for pH-triggered drug release and cancer chemotherapy. These prodrugs could be successfully produced by chemically coupling hydrophobic deoxycholic acid (DCA) to dextran hydrazine (denoted as Dex-NHNH2) and hydrazone linker formation between doxorubicin (DOX) and Dex-NHNH2. These Dex-DCA-DOX prodrugs self-assembled to form micelles under physiological conditions with varied particle sizes depending on molecular weight of dextran, degree of substitution (DS) of DCA and DOX. After optimization, Dex10k-DCA9-DOX5.5 conjugate comprising dextran of 10kDa, DCA of DS 9 and DOX loading content of 5.5wt%, formed the micelles with the smallest size (110nm). These prodrug micelles could slowly liberate DOX under physiological conditions but efficiently released the drug at an acidified endosomal pH by the hydrolysis of acid-labile hydrazone linker. In vitro cytotoxicity experiment indicated that Dex10k-DCA9-DOX5.5 micelles exerted marked antitumor activity against MCF-7 and SKOV-3 cancer cells. Besides, intravenous administration of the micelles afforded growth inhibition of SKOV-3 tumor bearing in nude mice at a dosage of 2.5mg per kg with anti-cancer efficacy comparable to free DOX-chemotherapy but low systemic toxicity. This study highlights the feasibility of bio-safe and efficient dextran-based prodrug micelles designed for cancer chemotherapy.