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Reductively degradable α-amino acid-based poly(ester amide)-graft-galactose copolymers: facile synthesis, self-assembly, and hepatoma-targeting doxorubicin delivery.
- Source :
-
Biomaterials science [Biomater Sci] 2015 Jul; Vol. 3 (7), pp. 1134-46. Date of Electronic Publication: 2015 Apr 08. - Publication Year :
- 2015
-
Abstract
- Novel reductively degradable α-amino acid-based poly(ester amide)-graft-galactose (SSPEA-Gal) copolymers were designed and developed to form smart nano-vehicles for active hepatoma-targeting doxorubicin (DOX) delivery. SSPEA-Gal copolymers were readily synthesized via solution polycondensation reaction of di-p-toluenesulfonic acid salts of bis-l-phenylalanine 2,2-thiodiethanol diester and bis-vinyl sulfone functionalized cysteine hexanediol diester with dinitrophenyl ester of adipic acid, followed by conjugating with thiol-functionalized galactose (Gal-SH) via the Michael addition reaction. SSPEA-Gal formed unimodal nanoparticles (PDI = 0.10 - 0.12) in water, in which average particle sizes decreased from 138 to 91 nm with increasing Gal contents from 31.6 wt% to 42.5 wt%. Notably, in vitro drug release studies showed that over 80% DOX was released from SSPEA-Gal nanoparticles within 12 h under an intracellular mimicking reductive conditions, while low DOX release (<20%) was observed for reduction-insensitive PEA-Gal nanoparticles under otherwise the same conditions and SSPEA-Gal nanoparticles under non-reductive conditions. Notably, SSPEA-Gal nanoparticles exhibited high specificity to asialoglycoprotein receptor (ASGP-R)-overexpressing HepG2 cells. MTT assays using HepG2 cells showed that DOX-loaded SSPEA-Gal had a low half maximal inhibitory concentration (IC50) of 1.37 μg mL(-1), approaching that of free DOX. Flow cytometry and confocal laser scanning microscopy studies confirmed the efficient uptake of DOX-loaded SSPEA-Gal nanoparticles by HepG2 cells as well as fast intracellular DOX release. Importantly, SSPEA-Gal and PEA-Gal nanoparticles were non-cytotoxic to HepG2 and MCF-7 cells up to a tested concentration of 1.0 mg mL(-1). These tumor-targeting and reduction-responsive degradable nanoparticles have appeared as an interesting multi-functional platform for advanced drug delivery.
- Subjects :
- Antineoplastic Agents metabolism
Antineoplastic Agents pharmacology
Asialoglycoprotein Receptor metabolism
Carcinoma, Hepatocellular chemistry
Carcinoma, Hepatocellular metabolism
Doxorubicin administration & dosage
Doxorubicin metabolism
Doxorubicin pharmacology
Drug Carriers chemistry
Drug Delivery Systems
Drug Liberation
Galactose chemistry
Hep G2 Cells
Humans
MCF-7 Cells
Micelles
Phenylalanine pharmacology
Polymers chemistry
Asialoglycoprotein Receptor chemistry
Carcinoma, Hepatocellular drug therapy
Doxorubicin chemistry
Drug Carriers administration & dosage
Galactose pharmacology
Nanoparticles chemistry
Phenylalanine chemistry
Polyamines chemistry
Polyesters chemistry
Polymers pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 2047-4849
- Volume :
- 3
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Biomaterials science
- Publication Type :
- Academic Journal
- Accession number :
- 26221946
- Full Text :
- https://doi.org/10.1039/c4bm00436a