Glutathione detonated and pH responsive nano-clusters of Au nanorods with a high dose of DOX for treatment of multidrug resistant cancer. (15th July 2018)

• Record Type: Journal Article
• Authors: Wang, Yun; Wang, Feihu; Liu, Ying; Xu, Shaohui; Shen, Yuanyuan; Feng, Nianping; Guo, Shengrong
• Is Part Of: Acta biomaterialia. Volume 75(2018)
• Page Start: 334
• Page End: 345
• Publication Date: 2018-07-15
• Subjects: AuNR or DOX-AuNR-PCDA-PEG-Biotin Au nanorods conjugated with doxorubicin and amphiphilic poly(curcumin-co-dithiodipropionic acid)-b-biotinylated poly(ethylene glycol) -- AuNR Cluster the nano-cluster of Au nanorods conjugated with doxorubicin and amphiphilic poly(curcumin-co-dithiodipropionic acid)-b-biotinylated poly(ethylene glycol) -- DOX doxorubicin -- CUR curcumin -- PCDA poly(curcumin-co-dithiodipropionic acid) -- AuNR-CTAB cetyltrimethylammonium bromide-protected Au nanorods -- PPB or PCDA-PEG-Biotin poly(curcumin-co-dithiodipropionic acid)-b-biotinylated poly(ethylene glycol) -- GSH glutathione -- MDR multidrug resistance -- P-gp P-glycoprotein -- LA-Hyd-DOX hydrazone of α-lipoyl hydrazine and doxorubicin; Au nanorods -- Nano-clusters -- Doxorubicin -- Glutathione responsive disintegration -- MCF-7/ADR cells; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1016/j.actbio.2018.06.012
• Languages: English
• ISSNs: 1742-7061

Abstract

Graphical abstract: Abstract: Effects of nanosized drug delivery systems on cancer are often compromised due to their low drug loadings, premature drug release and multi-drug resistance (MDR). Herein, we reported a glutathione detonated and pH responsive nano-cluster of Au nanorods (AuNRs) with chemotherapeutic doxorubicin (DOX) and pre-chemosensitizer polycurcumin to treat MCF-7/ADR cells. The nano-cluster was prepared by self-assembling of AuNRs conjugated with DOX and amphiphilic poly(curcumin-co-dithiodipropionic acid)-b-biotinylated poly(ethylene glycol) via an emulsion/solvent evaporation technique, termed AuNR Cluster. The AuNR Cluster had a high drug loading (31.5% DOX), presenting much better aqueous solubility and stability at physiological pH than their individual AuNRs. The AuNR Cluster could be detonated to be their individual AuNRs at an intracellular concentration level of glutathione (GSH) (5 mM) and triggered to release DOX at an acidic pH (pH 6.8 or 5.0), which effectively facilitated cellular uptake of DOX (607 vs 356 a.u. for AuNRs at 12 h) and inhibited DOX efflux (471.33 vs 39.17 a.u. for free DOX at 24 h). The IC50 value of DOX against MCF-7/ADR cells for AuNR Cluster was 4.15 µg/mL, much lower than that for free DOX (90.97 µg/mL). The AuNR Cluster took much more photothermal effects than their corresponding AuNRs and presented enhanced anti-tumor effect (IC50 : 2.61 µg/mL) under 808 nm laser irradiation. Statement of Significance: Nano-sized drug delivery systems for anti-MDR cancer is still a challenging task. Herein, AuNR Cluster was self-assembled by individual AuNRs via emulsion/solvent evaporation technique, having a structure consisting of hydrophobic DOX/PCDA-AuNR core and hydrophilic biotin-PEG chain shell. AuNR Cluster is detonated to disintegrate and yield its individual AuNRs at an intracellular concentration level of glutathione (5 mM) and triggered to release DOX at an acidic pH (6.8 or 5.0). In comparison with its individual AuNRs, AuNR Cluster has better water solubility and stability, greater photothermal effects under NIR irradiation, bigger cytotoxicity against MCF-7/ADR cells. AuNR Cluster is expected to be a potential nanomedicine for treatment of MDR cancer.