Efficient intracellular delivery of functional proteins using cationic polymer core/shell nanoparticles.
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.
Lee
Ashlynn L Z
AL
Institute of Bioengineering and Nanotechnology, The Nanos 04-01, Singapore.
Wang
Yong
Y
Ye
Wen-Hui
WH
Yoon
Ho Sup
HS
Chan
Sui Yung
SY
Yang
Yi-Yan
YY
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D001693:Biological Transport, Active; D002412:Cations; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems; D004563:Electrochemistry; D006367:HeLa Cells; D006801:Humans; D008422:Materials Testing; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D010316:Particle Size; D037121:Plant Lectins / Q000008:administration & dosage / Q000493:pharmacokinetics; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D011506:Proteins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013347:Subcellular Fractions / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D001672:Biocompatible Materials; D002412:Cations; D037121:Plant Lectins; D011108:Polymers; D011506:Proteins