title: Injectable Hydrogel-Microsphere Construct with Sequential Degradation for Locally Synergistic Chemotherapy.
abstract: In recent years, in situ chemotherapy mediated by biodegradable polymer platforms has attracted increased attention. Herein, an advanced drug delivery system, combretastatin A-4 (CA4) and docetaxel (DTX)-loaded microsphere embedded in injectable thermosensitive polypeptide hydrogel (i.e., hydrogel-microsphere (Gel-MP) construct), was reported for sequential release of drugs with different mechanisms to treat osteosarcoma synergistically. The Gel-MP construct showed sequential biodegradability and excellent biocompatibility. CA4 was preferentially released from hydrogel with faster degradation to disturb the vascular structure of the tumor and reduce the exchange of nutrients between the tumor and surrounding tissues, which created interstitial space in the tissue for DTX penetration to inhibit tumor cell proliferation. The in vivo treatment with Gel/CA4-MP/DTX efficiently suppressed the growth of mouse K7 osteosarcoma compared to other formulations. More importantly, by systematical study of histopathology and immunohistochemistry, the Gel-MP construct can significantly upregulate antiproliferation effect and reduce toxicity of drugs. Therefore, this injectable and locally sequential delivery system has a bright prospect in clinical application of in situ synergistic chemotherapy.
authors.affiliation: Department of Orthopedics, Second Hospital of Jilin University , Changchun 130041, People's Republic of China.|Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, People's Republic of China.
authors.forename: Yuhao
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, People's Republic of China.
authors.forename: Yilong
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, People's Republic of China.
authors.forename: Jinjin
authors.initials: J
authors.lastname: Chen
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, People's Republic of China.
authors.forename: Jianxun
authors.identifier: http://orcid.org/0000-0002-5232-8863
authors.initials: J
authors.lastname: Ding
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, People's Republic of China.
authors.forename: Mingqiang
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Second Hospital of Jilin University , Changchun 130041, People's Republic of China.
authors.forename: Chen
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Second Hospital of Jilin University , Changchun 130041, People's Republic of China.
authors.forename: Jin-Cheng
authors.initials: JC
authors.lastname: Wang
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, People's Republic of China.
authors.forename: Xuesi
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D004339:Drug Compounding; D016503:Drug Delivery Systems; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D020100:Hydrogels; D051379:Mice; D008863:Microspheres; D011108:Polymers
chemical_list: D020100:Hydrogels; D011108:Polymers; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate
keywords: microsphere; osteosarcoma; sequential drug release; synergistic chemotherapy; thermosensitive hydrogel