title: Selectively Sensitizing Malignant Cells to Photothermal Therapy Using a CD44-Targeting Heat Shock Protein 72 Depletion Nanosystem.
abstract: Selectively enhance the therapeutic efficacy to malignancy is one of the most important issues for photothermal therapy (PTT). However, most solid tumors, such as triple negative breast cancer (TNBC), do not have identifiable surface markers to distinguish themselves from normal cells, thus it is challenging to selectively identify and eliminate those malignances by PTT. In this report, we hypothesized that, by targeting CD44 (one TNBC-overexpressed surface molecule) and depleting heat shock protein 72 (HSP72, one malignancy-specific-overexpressed thermotolerance-related chaperone) subsequently, the TNBC could be selectively sensitized to PTT and improve the accuracy of treatment. To this end, a rationally designed nanosystem gold nanostar (GNS)/siRNA against HSP72 (siHSP72)/hyaluronic acid (HA) was successfully constructed using a layer-by-layer method. Hydrodynamic diameter and zeta potential analysis demonstrated the formation of GNS/siHSP72/HA having a particle size of 73.2 ± 3.8 nm and a negative surface charge of -18.3 ± 1.6 mV. The CD44-targeting ability of GNS/siHSP72/HA was confirmed by the flow cytometer, confocal microscopic imaging, and competitive binding analysis. The HSP72 silencing efficacy of GNS/siHSP72/HA was ∼95% in complete culture medium. By targeting CD44 and depleting HSP72 sequentially, GNS/siHSP72/HA could selectively sensitize TNBC cells to hyperthermia and enhance the therapeutic efficacy to TNBC with minimal side effect both in vitro and in vivo. Other advantages of GNS/siHSP72/HA included easy synthesis, robust siRNA loading capacity, endosome/lysosome escaping ability, high photothermal conversion efficacy and superior hemo- and biocompatibility.
authors: Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University , Nanjing 210002, P.R. China.|State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, P.R. China.
authors: Shouju
authors: S
authors: Wang
authors: Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University , Nanjing 210002, P.R. China.|State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, P.R. China.
authors: Ying
authors: Y
authors: Tian
authors: Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University , Nanjing 210002, P.R. China.
authors: Wei
authors: W
authors: Tian
authors: Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University , Nanjing 210002, P.R. China.
authors: Jing
authors: J
authors: Sun
authors: Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University , Nanjing 210002, P.R. China.
authors: Shuang
authors: S
authors: Zhao
authors: Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University , Nanjing 210002, P.R. China.
authors: Ying
authors: Y
authors: Liu
authors: Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University , Nanjing 210002, P.R. China.
authors: Chunyan
authors: C
authors: Wang
authors: Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University , Nanjing 210002, P.R. China.|State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, P.R. China.
authors: Yuxia
authors: Y
authors: Tang
authors: PLA Cancer Center of Nanjing Bayi Hospital , Nanjing 210002, P.R. China.
authors: Xingqun
authors: X
authors: Ma
authors: Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University , Nanjing 210002, P.R. China.|State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, P.R. China.
authors: Zhaogang
authors: Z
authors: Teng
authors: Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University , Nanjing 210002, P.R. China.|State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, P.R. China.
authors: Guangming
authors: G
authors: Lu
mesh_terms: D045744:Cell Line, Tumor; D006046:Gold; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D006979:Hyperthermia, Induced; D053768:Metal Nanoparticles; D009369:Neoplasms / Q000628:therapy; D010789:Phototherapy; D021381:Protein Transport
chemical_list: C497483:CD44 protein, human; D050884:HSP72 Heat-Shock Proteins; D018960:Hyaluronan Receptors; D006046:Gold
keywords: gene therapy; heat shock protein; photothermal therapy; thermotolerance; triple negative breast cancer