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  • Salvinorin A P H Tran T T Tran B J Lee

    2019-10-22

    [63] P.H. Tran, T.T. Tran, B.J. Lee, Biodistribution and pharmacokinetics in rats and antitumor effect in various types of tumor-bearing mice of novel self-assembled gelatin-oleic Salvinorin A nanoparticles containing paclitaxel, J. Biomed. Nanotechnoly. 10 (2014) 154–165.
    [64] X.Y. Zhang, Y.D. Zhang, Enhanced antiproliferative and apoptosis effect of pacli-taxel-loaded polymeric micelles against non-small cell lung cancers, Tumour Biol. 36 (2015) 4949–4959.
    Contents lists available at ScienceDirect
    Carbohydrate Polymers
    journal homepage: www.elsevier.com/locate/carbpol
    A novel pH-sensitive targeting polysaccharide-gold nanorod conjugate for T combined photothermal-chemotherapy of breast cancer
    Guanghui Houa, Junmin Qiana, , Weijun Xua, Tiantian Suna, Yaping Wanga, Jinlei Wanga, Lijie Jia, Aili Suob,
    a State Key Laboratory for Mechanical Behavior of Materials, Xi’an Jiaotong University, Xi’an, 710049, China
    b Department of Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, China
    Keywords:
    Gold nanorod
    Hydroxyethyl chitosan
    Combined photothermal-chemotherapy Breast cancer 
    Chemo-photothermal combination therapy is a promising strategy for cancer treatment. In this study, to achieve the combined photothermal-chemotherapy of breast cancer, a pH-sensitive oxidized hyaluronic acid-decorated dihydroxyphenyl/hydrazide bifunctionalized hydroxyethyl chitosan (DHHC)-gold nanorod (GNR) conjugate was developed. DHHC was synthesized by successive dihydroxyphenylation and hydrazidation of hydroxyethyl chitosan through carbodiimide reaction and click chemistry, respectively. The conjugate was obtained by che-mically bonding DHHC onto GNR via Au-catechol bonds. Doxorubicin (DOX) was loaded onto the conjugate via an acid-labile hydrazone linkage with a drug loading content of 5.1%. DOX-loaded conjugate displayed good stability in neutral aqueous solutions and exhibited pH-responsive drug release and surface charge reversal behaviors. In vitro biological studies indicated that the conjugate could be effectively internalized by breast cancer MCF-7 cells and synergistic therapeutic effects were demonstrated, suggesting its great potential in combined photothermal-chemotherapy of breast cancer.
    1. Introduction
    The effective treatment of malignant tumors is still a huge challenge due to the uncontrolled malignant hyperplasia and rapid cancer me-tastasis. Recent studies suggest that the combination of chemotherapy and photothermal therapy can achieve better therapeutic efficacy than single-modality therapy because of its additive or synergistic effect (Chen, Liang, Wang, & Liu, 2015; Li et al., 2015; Wang, Chen et al., 2014). Gold nanorod (GNR), one of the most effective photothermal agents, has attracted extensive attention in cancer treatment due to its adjustable longitudinal surface plasmon resonance (LSPR) and high light-to-heat conversion efficiency (Luo et al., 2016, Li et al., 2013). The LSPR peak of GNR can be easily adjusted to the NIR region by changing its aspect ratio to convert NIR light energy into heat energy. Further-more, rod-shaped nanoparticles possess a prolonged circulation time in blood (Barua et al., 2013; Wang, Xu et al., 2014; Xu et al., 2017). Thus, GNR-based chemo-photothermal combination therapy is a desirable strategy to treat cancer. Unfortunately, the low specific surface area of GNR limits the loading amount of anti-cancer drug (Cheng et al., 2013; Lu et al., 2014). Furthermore, GNR synthesized by seed-growth method is capped by deleterious but necessary surfactant
    cetyltrimethylammonium bromide (CTAB) and shows poor stability under physiological conditions. (Niidome et al., 2006). This short-coming severely restricts its biomedical applications. To address the above-mentioned problem, various materials have been employed to decorate GNR, such as polyethylene glycol (PEG) (Li et al., 2013; Tao et al., 2014), polyethyleneimine (Wang et al., 2015), poly(sodium-p-styrenesulfonate) (And & Hafner, 2005; Liu, Zhao, Wang, & Chang, 2015) and mesoporous silica (Liu et al., 2013; Zhang, Qian, Wang, Wang, & He, 2013). These modified GNRs can support drugs and achieve combined photothermal chemotherapy. However, there still exist some shortcomings. For example, although hydrophilic PEG or negatively-charged polymer shells can ensure the stability of GNR under physiological conditions and avoid unwanted serum protein ad-sorption and clearance by reticulo-endothelial system (Blanco, Shen, & Ferrari, 2015), they inhibit the cellular internalization of nanoparticles due to either the shielding effect of PEG or the electrostatic repulsion between anionic polymer and negatively-charged plasma membranes (Guan et al., 2017). In contrast, positively-charged polymers can non-specifically interact with most serum proteins and cells, resulting in low drug accumulation in tumors and obvious toxic side effects towards normal tissues (Han et al., 2015). Additionally, chemotherapeutic drugs