title: Thermosensitive Hydrogel Co-loaded with Gold Nanoparticles and Doxorubicin for Effective Chemoradiotherapy.
abstract: Chemoradiotherapy, as a well-established paradigm to treat various cancers, still calls for novel strategies. Recently, gold nanoparticles (AuNPs) have been shown to play an important role as a radiosensitizer in cancer radiotherapy. The aim of this study was to evaluate the combination of polyethylene glycol (PEG) modified AuNPs and doxorubicin (DOX) to improve cancer chemoradiotherapy, in which the AuNPs was the radiosensitizer and the DOX was the model chemotherapeutic. A Pluronic® F127-based thermosensitive hydrogel (Au-DOX-Gel) loading AuNPs and DOX was developed by "cold method" for intratumoral injection. The formulation was optimized at a F127 concentration of 22% for Au-DOX-Gel. The release profiles compared to a control group were assessed in vitro and in vivo. Au-DOX-Gel showed sustained release of AuNPs and DOX. The cell viability and surviving fraction of mouse melanoma (B16) and Human hepatocellular liver carcinoma (HepG2) cells were significantly inhibited by the combination treatment of DOX and AuNPs under radiation. Tumor sizes of mice were significantly decreased by Au-DOX-Gel compared to controls. Interestingly, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and Ki-67 staining results showed that tumor cell growth and proliferation were inhibited by AuNPs combined with DOX under radiation, suggesting that the radiosensitization activity and combination effects might be caused by inhibition of tumor cell growth and proliferation. Furthermore, the results of skin safety tests, histological observation of organs, and the body weight changes indicated in vivo safety of Au-DOX-Gel. In conclusion, the Au-DOX-Gel developed in this study could represent a promising strategy for improved cancer chemoradiotherapy.
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Science, Shandong University, Jinan, 250012, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Li
authors.affiliation: Key Lab of Colloid and Interface Chemistry, Ministry of Education, Department of Chemistry and Chemical Engineering, Shandong University, Jinan, 250199, China.
authors.forename: Mingfu
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Radiation, Qilu Hospital of Shandong University, Jinan, 250012, China.
authors.forename: Jianzhen
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Science, Shandong University, Jinan, 250012, China.
authors.forename: Tianqi
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Science, Shandong University, Jinan, 250012, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Radiation, Qilu Hospital of Shandong University, Jinan, 250012, China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Institute of Immunopharmacology & Immunotherapy, School of Pharmaceutical Sciences, Shandong University, Jinan, 250012, China.
authors.forename: Cai
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Science, Shandong University, Jinan, 250012, China. zhangnancy9@sdu.edu.cn.
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry; D001835:Body Weight / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D006046:Gold / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D008546:Melanoma, Experimental; D053768:Metal Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice; D020442:Poloxamer; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013696:Temperature
chemical_list: D000903:Antibiotics, Antineoplastic; D020100:Hydrogels; D011838:Radiation-Sensitizing Agents; D020442:Poloxamer; D006046:Gold; D004317:Doxorubicin
keywords: chemoradiotherapy; doxorubicin; gold nanoparticles; thermosensitive hydrogel