4.8 Article

Release of Photoactivatable Drugs from Plasmonic Nanoparticles for Targeted Cancer Therapy

Journal

ACS NANO
Volume 5, Issue 10, Pages 7796-7804

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/nn201592s

Keywords

aptamer; gold nanoparticle; controlled drug release; targeted cancer therapy; photothermal effect

Funding

  1. National Tsing Hua University [99N2947E1, 99N82531E1]
  2. National Science Council of Taiwan, ROC [98-2113-M-007-003, 99-2113-M-007-006-MY2, 99-2627-M-007-010]

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Chemotherapy Is an important modality In cancer treatment. The major challenges of recent works are to improve drug loading, increase selectivity to target cells, and control the precise release of drugs. In the present study, we devised a smart drug carder, an aptamer/hairpin DNA gold nanopaticle (apt/hp-Au NP) conjugate for targeted delivery of drugs. The DNA aptamer sgc8c, which possesses strong affinity for protein tyrosine kinase 7 (PTK7), abundantly expressed on the surface of CCRF-CEM (T-cell acute lymphoblastic leukemia) cells, was assembled onto the surface of Au NPs. The repeated d(CGATCG) sequence within the hpDNA on the Au NP surface was used for the loading of the anticancer drug doxorubidn (Dot). After optimization, 25 (+/- 3) sgc8c and 305 (+/- 9) Dot molecules were successfully loaded onto the AuNP (13 nm) surface. The binding capability of apt/hp-Au NP conjugates toward targeted cells was Investigated by flow cytometry and atomic absorption spectroscopy, which showed that the aptamer-functionalized nanoconjugates were selective for targeting of cancer cells. A cell toxicity (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, MTT) assay also demonstrated that these drugloaded nanoconjugates could kill targeted cancer cells more effectively than nontargeted (control) cells. Most importantly, when illuminated with plasmon-resonant light (532 nm), Dox:nanoconjugates displayed enhanced antitumor efficacy with few side effects. The marked release of Dox from these nanoconjugates In living cells was monitored by increasing fluorescence signals upon light exposure. In vitro studies confirmed that aptamer-functionalized hp-Au NPs can be used as carriers for targeted delivery of drugs with remote control capability by laser Irradiation with high spatial/temporal resolution.

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