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Lactobionic/Folate Dual-Targeted Amphiphilic Maltodextrin-Based Micelles for Targeted Codelivery of Sulfasalazine and Resveratrol to Hepatocellular Carcinoma.
Lactobionic/Folate Dual-Targeted Amphiphilic Maltodextrin-Based Micelles for Targeted Codelivery of Sulfasalazine and Resveratrol to Hepatocellular Carcinoma.
- Source :
-
Bioconjugate chemistry [Bioconjug Chem] 2018 Sep 19; Vol. 29 (9), pp. 3026-3041. Date of Electronic Publication: 2018 Aug 27. - Publication Year :
- 2018
-
Abstract
- In this study, promising approaches of dual-targeted micelles and drug-polymer conjugation were combined to enable injection of poorly soluble anticancer drugs together with site-specific drug release. Ursodeoxycholic acid (UDCA) as a hepatoprotective agent was grafted to maltodextrin (MD) via carbodiimide coupling to develop amphiphilic maltodextrin-ursodeoxycholic acid (MDCA)-based micelles. Sulfasalazine (SSZ), as a novel anticancer agent, was conjugated via a tumor-cleavable ester bond to MD backbone to obtain tumor-specific release, whereas resveratrol (RSV) was physically entrapped within the hydrophobic micellar core. For maximal tumor-targeting, both folic acid (FA) and lactobionic acid (LA) were coupled to the surface of micelles to obtain dual-targeted micelles. The decrease of critical micelle concentration (CMC) from 0.012 to 0.006 mg/mL declares the significance of a dual hydrophobicized core of micelles by both UDCA and SSZ. The dual-targeted micelles showed a great hemocompatibility, as well as enhanced cytotoxicity and internalization into HepG-2 liver cancer cells via binding to overexpressed folate and asialoglycoprotein receptors. In vivo, the micelles demonstrated superior antitumor effects revealed as reduction in the liver/body weight ratio, inhibition of angiogenesis, and enhanced apoptosis. Overall, combined strategies of dual active targeted micelles with bioresponsive drug conjugation could be utilized as a promising approach for tumor-targeted drug delivery.
- Subjects :
- Animals
Antineoplastic Agents therapeutic use
Carcinoma, Hepatocellular pathology
Hep G2 Cells
Humans
Liver Neoplasms pathology
Mice
Resveratrol therapeutic use
Sulfasalazine therapeutic use
Xenograft Model Antitumor Assays
Antineoplastic Agents administration & dosage
Carcinoma, Hepatocellular drug therapy
Disaccharides chemistry
Drug Delivery Systems
Folic Acid chemistry
Liver Neoplasms drug therapy
Micelles
Polysaccharides chemistry
Resveratrol administration & dosage
Sulfasalazine administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1520-4812
- Volume :
- 29
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Bioconjugate chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 30110148
- Full Text :
- https://doi.org/10.1021/acs.bioconjchem.8b00428