title: Heparin-functionalized Pluronic nanoparticles to enhance the antitumor efficacy of sorafenib in gastric cancers.
abstract: In this study, chitosan/heparin immobilized delivery system was developed for the delivery of sorafenib in gastric cancers. The SRF NP was nanosized with spherical outfit and present in the amorphous form. The SRF NP exhibited a sustained release of drug at pH 7.4 conditions and enhanced drug released at pH 5.5 conditions. Flow cytometer analysis showed that cellular uptake of NP increased two-fold after 4h of incubation compared to 1h incubation. The SRF NP showed superior anticancer effect compared to that of free SRF in BGC-823 cancer cells. SRF NP induced a remarkable apoptosis of cancer cells consistent with the cytotoxicity assay. Approximately, ∼ 50% of cell fractions were observed in early apoptosis phase with ∼ 15% of cells in the late apoptosis stage. Consistently, SRF NP exhibited a strong band for caspase-3 and P-53 than compared to free SRF in MGC-823 cancer cells. Importantly, SRF NP showed superior anticancer effect in xenograft tumor model making it a promising delivery vehicle in the treatment of gastric cancers.
authors.affiliation: Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China; Beijing Key Laboratory of Cancer Invasion and Metastasis Research & National Clinical Research Center of Digestive Diseases, Beijing 100050, China.
authors.forename: Ying-Chi
authors.initials: YC
authors.lastname: Yang
authors.affiliation: Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China; Beijing Key Laboratory of Cancer Invasion and Metastasis Research & National Clinical Research Center of Digestive Diseases, Beijing 100050, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China; Beijing Key Laboratory of Cancer Invasion and Metastasis Research & National Clinical Research Center of Digestive Diseases, Beijing 100050, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yin
authors.affiliation: Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China; Beijing Key Laboratory of Cancer Invasion and Metastasis Research & National Clinical Research Center of Digestive Diseases, Beijing 100050, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China; Beijing Key Laboratory of Cancer Invasion and Metastasis Research & National Clinical Research Center of Digestive Diseases, Beijing 100050, China.
authors.forename: Kang-Li
authors.initials: KL
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China; Beijing Key Laboratory of Cancer Invasion and Metastasis Research & National Clinical Research Center of Digestive Diseases, Beijing 100050, China. Electronic address: zhongtaozt@hotmail.com.
authors.forename: Zhong-Tao
authors.initials: ZT
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D005260:Female; D006493:Heparin / Q000737:chemistry*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000009:adverse effects / Q000737:chemistry*; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D020442:Poloxamer / Q000737:chemistry*; D000077157:Sorafenib; D013274:Stomach Neoplasms / Q000188:drug therapy
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D020442:Poloxamer; D009536:Niacinamide; D006493:Heparin; D000077157:Sorafenib
keywords: Anticancer therapy; Apoptosis; Gastric cancer; Pluronic NP; Sorafenib