Overcoming photodynamic resistance and tumor targeting dual-therapy mediated by indocyanine green conjugated gold nanospheres

• Published in: Journal of controlled release 2017-07, Vol.258, p.171-181
• Main Authors: Li, Wei, Guo, Xiaomeng, Kong, Fenfen, Zhang, Hanbo, Luo, Lihua, Li, Qingpo, Zhu, Chunqi, Yang, Jie, Du, Yongzhong, You, Jian
• Format: Article
• Language: English
• Subjects: Animals; Cell Line, Tumor; Coloring Agents - administration & dosage; Coloring Agents - chemistry; Coloring Agents - therapeutic use; Combined Modality Therapy - methods; Drug Delivery Systems; Gold - chemistry; Hollow gold nanospheres; Humans; Hyperthermia, Induced - methods; Indocyanine green; Indocyanine Green - administration & dosage; Indocyanine Green - chemistry; Indocyanine Green - therapeutic use; Mice; Mice, Inbred BALB C; Nanospheres - chemistry; Neoplasms - metabolism; Neoplasms - therapy; Peptides - administration & dosage; Peptides - chemistry; Peptides - therapeutic use; Photochemotherapy - methods; Photodynamic resistance; Photodynamic therapy; Photothermal therapy; Reactive Oxygen Species - metabolism
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2017.05.015

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. A tumor targeting dual-therapy nanosystem overcoming photodynamic resistance mediated by indocyanine green conjugated gold nanospheres. [Display omitted]