A dual-targeted hyaluronic acid-gold nanorod platform with triple-stimuli responsiveness for photodynamic/photothermal therapy of breast cancer. (1st January 2019)

• Record Type: Journal Article
• Authors: Xu, Weijun; Qian, Junmin; Hou, Guanghui; Wang, Yaping; Wang, Jinlei; Sun, Tiantian; Ji, Lijie; Suo, Aili; Yao, Yu
• Is Part Of: Acta biomaterialia. Volume 83(2019)
• Page Start: 400
• Page End: 413
• Publication Date: 2019-01-01
• Subjects: Photodynamic and photothermal dual-therapy -- Triple-responsive drug release -- Targeted delivery -- Gold nanorod -- Hyaluronic acid; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1016/j.actbio.2018.11.026
• Languages: English
• ISSNs: 1742-7061

Abstract

Graphical abstract: Abstract: Multi-stimuli-responsive theranostic nanoplatform integrating functions of both imaging and multimodal therapeutics holds great promise for improving diagnosis and therapeutic efficacy. In this study, we reported a pH, glutathione (GSH) and hyaluronidase (HAase) triple-responsive nanoplatform for HER2 and CD44 dual-targeted and fluorescence imaging-guided PDT/PTT dual-therapy against HER2-overexpressed breast cancer. The nanoplatform was fabricated by functionalizing gold nanorods (GNRs) with hyaluronic acid (HA) bearing pendant hydrazide and thiol groups via Au-S bonds, and subsequently chemically conjugating 5-aminolevulinic acid (ALA), Cy7.5 and anti-HER2 antibody onto HA moiety for PDT, fluorescence imaging and active targeting, respectively. The resulting versatile nanoplatform GNR-HA −ALA/Cy7.5 -HER2 had uniform sizes, favorable dispersibility, as well as pH, GSH and HAase triple-responsive drug release manner. In vitro studies demonstrated that HER2 and CD44 receptor-mediated dual-targeting strategy could significantly enhance the cellular uptake of GNR-HA −ALA/Cy7.5 -HER2. Under near-infrared (NIR) irradiation, MCF-7 cells could efficiently generate reactive oxygen species (ROS) and heat, and be more efficiently killed by a combination of PDT and PTT as compared with individual therapy. Pharmacokinetic and biodistribution studies showed that the nanoplatform possessed a circulation half-life of 1.9 h and could be specifically delivered to tumor tissues with an accumulation ratio of 12.8%. Upon the fluorescence imaging-guided PDT/PTT treatments, the tumors were completely eliminated without obvious side effects. The results suggest that the GNR-HA −ALA/Cy7.5 -HER2 holds great potential for breast cancer therapy. Statement of significance: A combination of photodynamic therapy (PDT) and photothermal therapy (PTT) is emerging as a promising cancer treatment strategy. However, its therapeutic efficacy is compromised by the nonspecific delivery and unintended release of photo-responsive agents. Herein, we developed a multifunctional theranostic nanoplatform GNR-HA −ALA/Cy7.5 -HER2 with pH, glutathione and hyaluronidase triple-responsive drug release for HER2 and CD44 dual-targeted and fluorescence imaging-guided PDT/PTT therapy against breast cancer. We demonstrated that HER2 and CD44 receptors-mediated dual-targeting strategy significantly enhanced the cellular uptake of GNR-HA −ALA/Cy7.5 -HER2. We also demonstrated that the combined PDT/PTT treatment had significantly superior antitumor effect than PDT or PTT alone both in vitro and in vivo . Therefore, GNR-HA −ALA/Cy7.5 -HER2 could serve as a promising nanoplatform for HER2-positive breast cancer therapy.