Facile Strategy by Hyaluronic Acid Functional Carbon Dot-Doxorubicin Nanoparticles for CD44 Targeted Drug Delivery and Enhanced Breast Cancer Therapy

Publication date: Available online 5 February 2020Source: International Journal of PharmaceuticsAuthor(s): Jianping Li, Man Li, Lifeng Tian, Yue Qiu, Qianwen Yu, Xuhui Wang, Rong Guo, Qin HeAbstractA facile approach was developed to synthesize an innovative hyaluronic acid-modified carbon dot-doxorubicin nanoparticles drug delivery platform. CD44 targeted HA-modified carbon dots (HA-CDs) were synthesized as carrier by one-step hydrothermal treatment within one hour with citric acid and branch-PEI as core carbon source. HA not only functioned as carbon dot component but also as hydrophilic group and targeting ligand of this system. The as-prepared HA-CDs were then loaded with doxorubicin (HA-CD@p-CBA-DOX) via an acid-cleavable bond, which released drug in a pH-responsive manner. In in vitro experiments, HA-CD@p-CBA-DOX displayed good hemocompatibility and serum stability, while exhibited high cytotoxicity on 4T1 cells. The confocal laser scanning microscopy and flow cytometry results demonstrated that DOX-loaded nanoparticles were internalized by 4T1 cells via HA-mediated CD44-targeting effect. The enhanced in vivo tumor accumulation of HA-CD@p-CBA-DOX was testified by live imaging. Compared with free DOX, superior in vivo anti-tumor efficacy of HA-CD@p-CBA-DOX was observed in both heterotopic and orthotopic 4T1 cell tumor models. Furthermore, blood hematology and blood biochemistry analysis demonstrated that HA-CD@p-CBA-DOX did not induce noticeable toxicity, which further co...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research