title: Doxorubicin-loaded polysaccharide nanoparticles suppress the growth of murine colorectal carcinoma and inhibit the metastasis of murine mammary carcinoma in rodent models.
abstract: As a synergistic drug combination, doxorubicin-loaded cisplatin crosslinked polysaccharide-based nanoparticles (Dex-SA-DOX-CDDP) have demonstrated enhanced antitumor efficacy and reduced systemic toxicity via optimized biodistribution, controlled drug release, prolonged blood circulation, and improved tolerability, compared to the non-crosslinked nanoparticles or free doxorubicin. Herein, we apply the Dex-SA-DOX-CDDP nanoparticles as an efficient antitumor agent to treat colorectal and breast tumors in three different in vivo models, i.e. subcutaneously implanted colorectal carcinoma, dimethylhydrazine-induced autochthonous colorectal carcinoma, and metastatic mammary carcinoma, which more closely simulate the natural milieu of the original tumor with intact pathological and immunological responses. Based on the properties of this combination in higher tumor accumulation and penetrating efficiency, the Dex-SA-DOX-CDDP nanoparticles significantly decreased the tumor sizes in CT26 cell line xenograft tumors compared to control. In addition, the affected animals' lifespan was significantly extended after the Dex-SA-DOX-CDDP treatment, in the autochthonous colon cancer model. Moreover, with the aid of iRGD, Dex-SA-DOX-CDDP could effectively block primary tumor growth and prevent the metastasis of 4T1 murine mammary carcinoma. In conclusion, Dex-SA-DOX-CDDP nanoparticles remarkably inhibit growth of colorectal carcinoma and metastasis of mammary carcinoma in vivo, which provides potential application as a safe and efficient antitumor agent in treatment of these cancers.
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China.
authors.forename: Mingqiang
authors.initials: M
authors.lastname: Li
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.
authors.forename: Hai
authors.initials: H
authors.lastname: Sun
authors.affiliation: Laboratory Animal Center, Jilin University, Changchun 130012, PR China.
authors.forename: Huaiyu
authors.initials: H
authors.lastname: Liu
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA. Electronic address: yzhang@wakehealth.edu.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China. Electronic address: xschen@ciac.ac.cn.
authors.forename: Xuesi
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D003911:Dextrans / Q000737:chemistry; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005629:Frozen Sections; D008297:Male; D015674:Mammary Neoplasms, Animal / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D009362:Neoplasm Metastasis; D011134:Polysaccharides / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D003911:Dextrans; D011134:Polysaccharides; D004317:Doxorubicin; D002945:Cisplatin
keywords: Cancer model; Chemotherapy; Colorectal carcinoma; Doxorubicin; Mammary carcinoma; Metastasis