期刊
ACS NANO
卷 5, 期 2, 页码 738-747出版社
AMER CHEMICAL SOC
DOI: 10.1021/nn102278w
关键词
polymeric nanoparticles; click chemistry; cellular uptake; pharmacokinetics
类别
资金
- National Institutes of Health [HHSN268201000046C]
- National Science Foundation [DMR05-20415]
- National Cancer Institute [CA86307]
A series of multivalent, functional polymer nanoparticles with diagnostic/imaging units and targeting ligands for molecular targeting were synthesized with the loading of the chainend-functionalized GRGDS peptide targeting sequence (model system based on integrin alpha(v)beta(3)) ranging from 0 to 50%. Accurate structural and functional group control in these systems was achieved through a modular approach involving the use of multiple functionalized macromonomer/monomer units combined with living free radical polymerization. In cellulo results show an increase in uptake In alpha(v)beta(3) integrin-positive U87MG glioblastoma cells with increasing RGD loading and a possible upper limit on the effectiveness of the number of RGD peptides for targeting alpha(v)beta(3) Integrin. Significantly, this increased targeting efficiency is coupled with in vivo biodistribution results, which show decreased blood circulation and increased liver uptake with increasing RGD loading. The results demonstrate the importance of controlling ligand loading in order to achieve optimal performance for therapeutic and imaging applications for multivalent nanoparticle-based systems.
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