Molecular Targeting‐Mediated Mild‐Temperature Photothermal Therapy with a Smart Albumin‐Based Nanodrug

• Published in: Small (Weinheim an der Bergstrasse, Germany) Vol. 15; no. 33; pp. e1900501 - n/a
• Main Authors: Gao, Ge, Jiang, Yao‐Wen, Sun, Wei, Guo, Yuxin, Jia, Hao‐Ran, Yu, Xin‐Wang, Pan, Guang‐Yu, Wu, Fu‐Gen
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01-08-2019
• Subjects: Ablation; Accumulation; Anticancer properties; Charge reversal; Chemotherapy; combination therapy; Cyanine dyes; degradability; Disruption; Heat shock proteins; Hyperthermia; Infrared lasers; Liver; mild‐temperature photothermal therapy; Mitochondria; molecularly targeted therapy; Nanoparticles; Nanotechnology; Organs; pH‐responsive charge reversal; Serum albumin; Tumors; combination therapy; degradability; mild-temperature photothermal therapy; pH-responsive charge reversal; molecularly targeted therapy
• ISSN: 1613-6810; 1613-6829
• DOI: 10.1002/smll.201900501

Photothermal therapy (PTT) usually requires hyperthermia >50 °C for effective tumor ablation, which inevitably induces heating damage to the surrounding normal tissues/organs. Moreover, low tumor retention and high liver accumulation are the two main obstacles that significantly limit the efficacy and safety of many nanomedicines. To solve these problems, a smart albumin‐based tumor microenvironment‐responsive nanoagent is designed via the self‐assembly of human serum albumin (HSA), dc‐IR825 (a cyanine dye and a photothermal agent), and gambogic acid (GA, a heat shock protein 90 (HSP90) inhibitor and an anticancer agent) to realize molecular targeting‐mediated mild‐temperature PTT. The formed HSA/dc‐IR825/GA nanoparticles (NPs) can escape from mitochondria to the cytosol through mitochondrial disruption under near‐infrared (NIR) laser irradiation. Moreover, the GA molecules block the hyperthermia‐induced overexpression of HSP90, achieving the reduced thermoresistance of tumor cells and effective PTT at a mild temperature (<45 °C). Furthermore, HSA/dc‐IR825/GA NPs show pH‐responsive charge reversal, effective tumor accumulation, and negligible liver deposition, ultimately facilitating synergistic mild‐temperature PTT and chemotherapy. Taken together, the NIR‐activated NPs allow the release of molecular drugs more precisely, ablate tumors more effectively, and inhibit cancer metastasis more persistently, which will advance the development of novel mild‐temperature PTT‐based combination strategies.
A smart albumin‐based theranostic nanoagent composed of human serum albumin, dc‐IR825 (a cyanine dye and a photothermal agent), and gambogic acid (an HSP90 inhibitor and an effective anticancer drug) is fabricated, which can achieve the synergistic molecular targeting‐mediated mild‐temperature photothermal therapy and chemotherapy of cancer.