title: Polysarcosine brush stabilized gold nanorods for in vivo near-infrared photothermal tumor therapy.
abstract: Gold nanorods (AuNRs) are suitable candidates for photothermal therapy in vivo, because of their excellent ability to transfer near-infrared (NIR) light into heat. However, appropriate surface should be generated on AuNRs before their in vivo application because of the low colloidal stability in complicate biological environment and relatively strong toxicity compared to their pristine stabilizer cetyltrimethylammonium bromide. In the current study, polysarcosine (PS), a non-ionic hydrophilic polypeptoid whose structure is similar to polypeptides, bearing repeating units of natural α-amino acid, was used to stabilize AuNRs due to its excellent hydrophilicity and biocompatibility. Polysarcosine with optimized molecular weight was synthesized and used to modify AuNRs by traditional ligand exchange. The grafting of PS on AuNRs was evidenced by fourier transform infrared (FTIR) spectroscopy and the alternation of surface zeta potential. The polysarcosine coated AuNRs (Au@PS) showed good stabilities in wide pH range and simulated physiological buffer with the ligand competition of dithiothreitol (DTT). The Au@PS NRs had neglectable cytotoxicity and showed efficient ablation of tumor cells in vitro. Moreover, Au@PS NRs had a longer circulation time in body that resulted in a higher accumulation in solid tumors after intravenous injection, compared to AuNRs capped with polyethylene glycol (PEG). Photothermal therapy in vivo demonstrated that the tumors were completely destroyed by single-time irradiation of NIR laser after one-time injection of the polysarcosine capped AuNRs. The Au@PS NRs did not cause obvious toxicity in vivo, suggesting promising potential in cancer therapy.
  
  
  
  In current study, polysarcosine (PS), a non-ionic hydrophilic polypeptoid whose structure is similar to polypeptides, bearing repeating units of natural α-amino acid, was used to stabilize AuNRs due to its excellent hydrophilicity and biocompatibility. The polysarcosine coated AuNRs (Au@PS) showed good stabilities in wide pH range and simulated physiological buffer. The Au@PS NRs had very low cytotoxicity and showed high efficacy for the ablation of cancer cells in vitro. Moreover, Au@PS NRs had a longer circulation time in blood that led to a higher accumulation in tumors after intravenous injection, compared to AuNRs capped with polyethylene glycol (PEG). In vivo photothermal therapy showed that tumors were completely cured without reoccurrence by one-time irradiation of NIR laser after a single injection of the polysarcosine modified AuNRs.
authors.affiliation: Institute of Pharmacology & Toxicology, College of Pharmaceutical Sciences, Zhejiang University, 866# Yuhangtang Road, Hangzhou 310058, China. Electronic address: hongzhu@zju.edu.cn.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhu
authors.affiliation: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, 38# Zheda Road, Hangzhou 310027, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Institute of Pharmacology & Toxicology, College of Pharmaceutical Sciences, Zhejiang University, 866# Yuhangtang Road, Hangzhou 310058, China.
authors.forename: Fang-Jie
authors.initials: FJ
authors.lastname: Yan
authors.affiliation: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, 38# Zheda Road, Hangzhou 310027, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Chen
authors.affiliation: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, 38# Zheda Road, Hangzhou 310027, China.
authors.forename: Xin-Feng
authors.initials: XF
authors.lastname: Tao
authors.affiliation: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, 38# Zheda Road, Hangzhou 310027, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ling
authors.affiliation: Institute of Pharmacology & Toxicology, College of Pharmaceutical Sciences, Zhejiang University, 866# Yuhangtang Road, Hangzhou 310058, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: Institute of Pharmacology & Toxicology, College of Pharmaceutical Sciences, Zhejiang University, 866# Yuhangtang Road, Hangzhou 310058, China.
authors.forename: Qiao-Jun
authors.initials: QJ
authors.lastname: He
authors.affiliation: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, 38# Zheda Road, Hangzhou 310027, China; State Key Laboratory of Molecular Engineering of Polymers (Fudan University), Yuejin Building, No. 220 Handan Road, Shanghai 200433, China. Electronic address: zwmao@zju.edu.cn.
authors.forename: Zheng-Wei
authors.initials: ZW
authors.lastname: Mao
mesh_terms: D000072283:A549 Cells; D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology; D001775:Blood Circulation; D002470:Cell Survival; D003102:Colloids / Q000737:chemistry; D006046:Gold / Q000737:chemistry*; D006979:Hyperthermia, Induced; D008024:Ligands; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D043942:Nanotubes / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000473:pathology / Q000628:therapy*; D010455:Peptides / Q000737:chemistry*; D010789:Phototherapy; D012521:Sarcosine / Q000031:analogs & derivatives* / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D019265:Spectroscopy, Near-Infrared; D014018:Tissue Distribution; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D001672:Biocompatible Materials; D003102:Colloids; D008024:Ligands; D010455:Peptides; C015475:polysarcosine; D006046:Gold; D012521:Sarcosine
keywords: Cancer treatment; Gold nanorods; Long circulation; Photothermal therapy; Polysarcosine