title: Overcoming the Heat Endurance of Tumor Cells by Interfering with the Anaerobic Glycolysis Metabolism for Improved Photothermal Therapy.
abstract: In this study, we developed a general method to decorate plasmonic gold nanorods (GNRs) with a CD44-targeting functional polymer, containing a hyaluronic acid (HA)-targeting moiety and a small molecule Glut1 inhibitor of diclofenac (DC), to obtain GNR/HA-DC. This nanosystem exhibited the superiority of selectively sensitizing tumor cells for photothermal therapy (PTT) by inhibiting anaerobic glycolysis. Upon specifically targeting CD44, sequentially time-dependent DC release could be achieved by the trigger of hyaluronidase (HAase), which abundantly existed in tumor tissues. The released DC depleted the Glut1 level in tumor cells and induced a cascade effect on cellular metabolism by inhibiting glucose uptake, blocking glycolysis, decreasing ATP levels, hampering heat shock protein (HSP) expression, and ultimately leaving malignant cells out from the protection of HSPs to stress (e.g., heat), and then tumor cells were more easy to kill. Owing to the sensitization effect of GNR/HA-DC, CD44 overexpressed tumor cells could be significantly damaged by PTT with an enhanced therapeutic efficiency in vitro and in vivo.
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry and ‡The Institute for Advanced Studies, Wuhan University , Wuhan 430072, People's Republic of China.
authors.forename: Wei-Hai
authors.initials: WH
authors.lastname: Chen
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry and ‡The Institute for Advanced Studies, Wuhan University , Wuhan 430072, People's Republic of China.
authors.forename: Guo-Feng
authors.initials: GF
authors.lastname: Luo
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry and ‡The Institute for Advanced Studies, Wuhan University , Wuhan 430072, People's Republic of China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Lei
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry and ‡The Institute for Advanced Studies, Wuhan University , Wuhan 430072, People's Republic of China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Hong
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry and ‡The Institute for Advanced Studies, Wuhan University , Wuhan 430072, People's Republic of China.
authors.forename: Wen-Xiu
authors.initials: WX
authors.lastname: Qiu
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry and ‡The Institute for Advanced Studies, Wuhan University , Wuhan 430072, People's Republic of China.
authors.forename: Li-Han
authors.initials: LH
authors.lastname: Liu
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry and ‡The Institute for Advanced Studies, Wuhan University , Wuhan 430072, People's Republic of China.
authors.forename: Si-Xue
authors.initials: SX
authors.lastname: Cheng
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry and ‡The Institute for Advanced Studies, Wuhan University , Wuhan 430072, People's Republic of China.
authors.forename: Xian-Zheng
authors.identifier: 0000-0001-6242-6005
authors.initials: XZ
authors.lastname: Zhang
mesh_terms: D000693:Anaerobiosis / Q000187:drug effects*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D019556:COS Cells; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004008:Diclofenac / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006019:Glycolysis / Q000187:drug effects*; D006046:Gold / Q000737:chemistry / Q000494:pharmacology; D006367:HeLa Cells; D006358:Hot Temperature; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry / Q000494:pharmacology; D061986:MCF-7 Cells; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D053768:Metal Nanoparticles / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D010789:Phototherapy; D000067996:RAW 264.7 Cells
chemical_list: D000970:Antineoplastic Agents; D004008:Diclofenac; D006046:Gold; D006820:Hyaluronic Acid
keywords: anaerobic glycolysis; gold nanorod; photothermal therapy; tumor targeting