Journal
BIOMATERIALS
Volume 35, Issue 24, Pages 6576-6584Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2014.04.043
Keywords
Dendrimer; Gold nanorods; Photothermal therapy; Chemotherapy; Doxorubicin
Funding
- Ministry of Education, Science, Sports, and Culture in Japan [23240075, 26242049]
- Grants-in-Aid for Scientific Research [25750177, 26242049, 23240075] Funding Source: KAKEN
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We prepared pH-sensitive drug dendrimer conjugate-hybridized gold nanorod as a promising platform for combined cancer photothermal-chemotherapy under in vitro and in vivo conditions. Poly(ethylene glycol)-attached PAMAM G4 dendrimers (PEG PAMAM) were first covalently linked on the surface of mercaptohexadecanoic acid-functionalized gold nanorod (MHA-AuNR), with subsequent conjugation of anti-cancer drug doxorubicin (DOX) to dendrimer layer using an acid-labile-hydrazone linkage to afford PEG-DOX-PAMAM-AuNR particles. The particles with a high PEG PAMAM dendrimer coverage density (0.28 per nm(2) AuNR) showed uniform sizes and excellent colloidal stability. In vitro drug release studies demonstrated that DOX released from PEG DOX PAMAM AuNR was negligible under normal physiological pH, but it was enhanced significantly at a weak acidic pH value. The efficient intracellular acid-triggered DOX release inside of lysosomes was confirmed using confocal laser scanning microscopy analysis. Furthermore, the combined photothermal-chemo treatment of cancer cells using PEG DOX PAMAM AuNR for synergistic hyperthermia ablation and chemotherapy was demonstrated both in vitro and in vivo to exhibit higher therapeutic efficacy than either single treatment alone, underscoring the great potential of PEG DOX PAMAM AuNR particles for cancer therapy. (C) 2014 Elsevier Ltd. All rights reserved.
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