Overcoming photodynamic resistance and tumor targeting dual-therapy mediated by indocyanine green conjugated gold nanospheres
Autor: | Jian You, Xiaomeng Guo, Hanbo Zhang, Qingpo Li, Lihua Luo, Yong-Zhong Du, Wei Li, Chunqi Zhu, Fenfen Kong, Jie Yang |
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Rok vydání: | 2016 |
Předmět: |
Indocyanine Green
Abcg2 medicine.medical_treatment media_common.quotation_subject Cell Pharmaceutical Science Photodynamic therapy Nanotechnology 02 engineering and technology 010402 general chemistry 01 natural sciences chemistry.chemical_compound Mice Drug Delivery Systems Cell Line Tumor Neoplasms medicine Animals Humans Internalization Coloring Agents media_common Mice Inbred BALB C biology Chemistry Photothermal effect Hyperthermia Induced Photothermal therapy 021001 nanoscience & nanotechnology Combined Modality Therapy eye diseases 0104 chemical sciences medicine.anatomical_structure Photochemotherapy Cancer cell biology.protein Cancer research Gold 0210 nano-technology Peptides Reactive Oxygen Species Indocyanine green Nanospheres |
Zdroj: | Journal of controlled release : official journal of the Controlled Release Society. 258 |
ISSN: | 1873-4995 |
Popis: | Photodynamic therapy (PDT) and photothermal therapy (PTT) have captured much attention due to the great potential to cure malignant tumor. Nevertheless, photodynamic resistance of cancer cells has limited the further efficacy of PDT. Unfortunately, the resistance mechanism and efforts to overcome the resistance still have been rarely reported so far. Here, we report a nanosystem with specific tumor targeting for combined PDT and PTT mediated by near-infrared (NIR) light, which was established by covalently conjugating indocyanine green (ICG) and TNYL peptide onto the surface of hollow gold nanospheres (HAuNS). Our nanosystem (TNYL-ICG-HAuNS) was proved to possess significantly increased light stability, reactive oxygen species (ROS) production and photothermal effect under NIR light irradiation, thus presenting a remarkably enhanced antitumor efficacy. The up-regulation of nuclear factor erythroid 2-related factor 2 (NFE2L2, Nrf2) in cancer cells during PDT induced a significant increase of ABCG2, NQO-1 and HIF-1α expression, causing PDT resistance of the cells. Interestingly, ABCG2 expression could almost keep a normal level in the whole PDT process mediated by TNYL-ICG-HAuNS. After repeated irradiations, TNYL-ICG-HAuNS could still produce almost constant ROS in cells while the Nrf2 expression reduced significantly. Furthermore, PDT resistance induced an obvious decrease of the internalization of free ICG, but didn't influence the cell uptake of TNYL-ICG-HAuNS. Our data explained that TNYL-ICG-HAuNS could overcome the photodynamic resistance of cancer cells, acting as a promising modality for simultaneous photothermal and photodynamic cancer therapy. |
Databáze: | OpenAIRE |
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