An Integrated Therapeutic Delivery System for Enhanced Treatment of Hepatocellular Carcinoma. (12th March 2018)

• Record Type: Journal Article
• Authors: Ye, Zhou; Wu, Wen‐Rui; Qin, Yu‐Fei; Hu, Jing; Liu, Chao; Seeberger, Peter H.; Yin, Jian
• Is Part Of: Advanced functional materials. Volume 28:Number 18(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-03-12
• Subjects: chemotherapy -- gene therapy -- hepatocellular carcinoma -- integrated delivery system -- targeting and tracking; Materials -- Periodicals; Chemical vapor deposition -- Periodicals; 620.11
• DOI: 10.1002/adfm.201706600
• Languages: English
• ISSNs: 1616-301X

Abstract

Abstract: Nanomaterials hold promise for the treatment of human carcinomas but integrating multiple functions into a single drug carrier system remains challenging. Herein, an integrated therapeutic delivery system for human hepatocellular carcinoma (HCC) treatment is reported, which is based on rhodamine B (RhB) end‐labeled cationic poly[2‐(dimethylamino)ethyl methacrylate] (PDMAEMA) and hydrophobic poly(3‐azido‐2‐hydroxypropyl methacrylate) (PGMA‐N3 ) segments equipped with a covalently bound galactose. This biocompatible and safe platform RhB‐PDMAEMA25‐c‐PGMA50‐Gal micelles (Gal‐micelles) offers four advantages: (1) Galactose ligands enhance cellular uptake by targeting the asialoglycoprotein receptor (ASGPR) that is overexpressed on HCC cell lines surfaces; (2) RhB end‐labeling facilitates real‐time imaging for tracking both in vitro and in vivo; (3) the acidic tumor microenvironment protonates the carrier system for efficient drug release as well as gene transfection, (4) codelivery of anticancer drug doxorubicin (DOX) and B‐cell lymphoma 2 small interfering RNA (Bcl‐2 siRNA) works synergistically against tumor growth in both subcutaneous and orthotopic HCC bearing mouse models. This integrated therapeutic delivery system holds potential for future clinical HCC treatment. Abstract : A novel integrated therapeutic delivery system for enhanced treatment of hepatocellular carcinoma in both subcutaneous and orthotopic tumor mouse models has been developed. Multiple functions are integrated into a single carrier, including codelivery and pH‐triggered release of drugs/small interfering RNA, hepatic targeting, fluorescent tracking, as well as biocompatibility and safety.