Mechanistic Insight into Cell Growth, Internalization, and Cytotoxicity of PAMAM Dendrimers

被引:45
作者
Parimi, Srinivas [1 ]
Barnes, Timothy J. [1 ]
Callen, David F. [2 ,3 ]
Prestidge, Clive A. [1 ]
机构
[1] Univ S Australia, Ian Wark Res Inst, ARC Special Res Ctr Particle & Mat Interfaces, Mawson Lakes, SA 5095, Australia
[2] Univ Adelaide, Discipline Med, Breast Canc Genet Grp, Adelaide, SA 5000, Australia
[3] Inst Med & Vet Sci, Hanson Inst, Adelaide, SA 5000, Australia
基金
澳大利亚研究理事会;
关键词
SUPPORTED LIPID-BILAYERS; POLY(PROPYLENE IMINE) DENDRIMERS; POLY(AMIDOAMINE) DENDRIMERS; POLYAMIDOAMINE DENDRIMERS; TRANSEPITHELIAL TRANSPORT; POLYCATIONIC POLYMERS; PEGYLATED LIPOSOMES; MEMBRANE TRANSPORT; HOLE FORMATION; DRUG-DELIVERY;
D O I
10.1021/bm9010134
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We report oil the role of PAMAM dendrimer concentration and generation (102, G4, G6) oil cell growth and cytotoxicity in HEK293T and HeLa cell lines and make comparisons with dendrimer-induced leakage from liposomes to probe the mechanisms in action Specifically, we observed it striking transition from cell growth enhancement to,I reduction in cell viability at a critical PAMAM dendrimer concentration, that is, similar to 500 nM. Confocal microscopy studies show evidence of I transition from cell membrane adhesion to cell Internalization and cell nucleus interaction at equivalent dendrimer concentrations A dendrimer concentration window of 500-700 nM was identified for effective cell Internalization without significant cytotoxicity Though liposome leakage con-elated with cytotoxicity, no quantitative agreement was observed, that is, cells are 100 times (based on surface coverage) more resistant to dendrimers than liposomes These findings have significant implications In the design of effective drug/gene delivery vehicles based oil dendrimers
引用
收藏
页码:382 / 389
页数:8
相关论文
共 54 条
[1]   An intrinsically fluorescent dendrimer as a nanoprobe of cell transport [J].
Al-Jamal, Khuloud T. ;
Ruenraroengsak, Pakatip ;
Hartell, Nicholas ;
Florence, Alexander T. .
JOURNAL OF DRUG TARGETING, 2006, 14 (06) :405-412
[2]   COMPLEXATION OF LECITHIN WITH CATIONIC POLYELECTROLYTES - PLASTIC MEMBRANES AS MODELS FOR THE STRUCTURE OF THE CELL-MEMBRANE [J].
ANTONIETTI, M ;
KAUL, A ;
THUNEMANN, A .
LANGMUIR, 1995, 11 (07) :2633-2638
[3]   Naphthalene Sulfonate Functionalized Dendrimers at the Solid-Liquid Interface: Influence of Core Type, Ionic Strength, and Competitive Ionic Adsorbates [J].
Barnes, Timothy J. ;
Ametov, Igor ;
Prestidge, Clive A. .
LANGMUIR, 2008, 24 (21) :12398-12404
[4]   Dendrimer adsorption on charged particulate surfaces [J].
Barnes, Timothy J. ;
Ametov, Igor ;
Prestidge, Clive A. .
ASIA-PACIFIC JOURNAL OF CHEMICAL ENGINEERING, 2008, 3 (01) :13-17
[5]   Antibacterial activities of poly(amidoamine) dendrimers terminated with amino and poly(ethylene glycol) groups [J].
Calabretta, Michelle K. ;
Kumar, Amit ;
McDermott, Alison M. ;
Cai, Chengzhi .
BIOMACROMOLECULES, 2007, 8 (06) :1807-1811
[6]   Interactions between dendrimer biocides and bacterial membranes [J].
Chen, CZS ;
Cooper, SL .
BIOMATERIALS, 2002, 23 (16) :3359-3368
[7]  
Deshayes Sebastien, 2007, V386, P299, DOI 10.1007/978-1-59745-430-8_11
[8]   Implications of the Dominant Role of Transporters in Drug Uptake by Cells [J].
Dobson, Paul D. ;
Lanthaler, Karin ;
Oliver, Stephen G. ;
Kell, Douglas B. .
CURRENT TOPICS IN MEDICINAL CHEMISTRY, 2009, 9 (02) :163-181
[9]   Dendrimer biocompatibility and toxicity [J].
Duncan, R ;
Izzo, L .
ADVANCED DRUG DELIVERY REVIEWS, 2005, 57 (15) :2215-2237
[10]   Transepithelial transport of poly(amidoamine) dendrimers across Caco-2 cell monolayers [J].
El-Sayed, M ;
Ginski, M ;
Rhodes, C ;
Ghandehari, H .
JOURNAL OF CONTROLLED RELEASE, 2002, 81 (03) :355-365