Efficient intracellular delivery of functional proteins using cationic polymer core/shell nanoparticles

Abstract Cationic core/shell nanoparticles self-assembled from biodegradable, cationic and amphiphilic copolymer poly{ N -methyldietheneamine sebacate)- co -[(cholesteryl oxocarbonylamido ethyl) methyl bis(ethylene) ammonium bromide] sebacate}, P(MDS- co -CES), were fabricated and employed to delive...

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Bibliographic Details
Published in:Biomaterials 2008-03, Vol.29 (9), p.1224-1232
Main Authors: Lee, Ashlynn L.Z, Wang, Yong, Ye, Wen-Hui, Yoon, Ho Sup, Chan, Sui Yung, Yang, Yi-Yan
Format: Article
Language:English
Subjects:
Advanced Basic Science
Antineoplastic Agents, Phytogenic - administration & dosage
Antineoplastic Agents, Phytogenic - pharmacokinetics
Biocompatible Materials - chemical synthesis
Biocompatible Materials - chemistry
Biocompatible Materials - pharmacokinetics
Biocompatible Materials - toxicity
Biological Transport, Active
Cationic core/shell nanoparticles
Cations
Cell Line
Cell Survival - drug effects
Dentistry
Drug Delivery Systems
Electrochemistry
HeLa Cells
Humans
Intracellular delivery
Lectin
Materials Testing
Nanoparticles - chemistry
Nanoparticles - toxicity
Particle Size
Plant Lectins - administration & dosage
Plant Lectins - pharmacokinetics
Polymers - chemical synthesis
Polymers - chemistry
Polymers - pharmacokinetics
Proteins
Proteins - administration & dosage
Proteins - pharmacokinetics
Subcellular Fractions - metabolism
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Summary:Abstract Cationic core/shell nanoparticles self-assembled from biodegradable, cationic and amphiphilic copolymer poly{ N -methyldietheneamine sebacate)- co -[(cholesteryl oxocarbonylamido ethyl) methyl bis(ethylene) ammonium bromide] sebacate}, P(MDS- co -CES), were fabricated and employed to deliver lectin A-chain, an anticancer glycoprotein. Lectin A-chain was efficiently bound onto the surfaces of the nanoparticles at high mass ratios of nanoparticles to lectin A-chain. The nanoparticle/lectin A-chain complexes had an average size of approximately 150 nm with zeta potential of about +30 mV at the mass ratio of 50 or above while the BioPorter/lectin A-chain complexes had a larger particle size and relatively lower zeta potential (150 nm vs. 455 nm; +30 mV vs. +20 mV). Therefore, the cellular uptake of nanoparticle/lectin A-chain complexes was much greater than that of BioPorter/lectin A-chain complexes. The results obtained from cytotoxicity tests show that lectin A-chain delivered by the nanoparticles was significantly more toxic against MDA-MB-231, HeLa, HepG2 and 4T1 cell lines when compared to BioPorter, and IC50 of lectin A-chain delivered by the nanoparticles was 0.2, 0.5, 10 and 50 mg/l, respectively, while that of lectin A-chain delivered by BioPorter was higher than 100 mg/l in all cell lines tested. These nano-sized particles may provide an efficient approach for intracellular delivery of biologically active proteins.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2007.11.021