title: Efficient antitumor effect of co-drug-loaded nanoparticles with gelatin hydrogel by local implantation.
abstract: Tetrandrine (Tet) could enhance the antitumor effect of Paclitaxel (Ptx) by increasing intracellular Reactive Oxygen Species (ROS) levels, which leads to the possibility of co-delivery of both drugs for synergistic antitumor effect. In the current study, we reported an efficient, local therapeutic strategy employing effective Tet and Ptx delivery with a nanoparticle-loaded gelatin system. Tet- and Ptx co-loaded mPEG-PCL nanoparticles (P/T-NPs) were encapsulated into the physically cross-linked gelatin hydrogel and then implanted on the tumor site for continuous drug release. The drug-loaded gelatin hydrogel underwent a phase change when the temperature slowly increased. In vitro study showed that Tet/Ptx-loaded PEG-b-PCL nanoparticles encapsulated within a gelatin hydrogel (P/T-NPs-Gelatin) inhibited the growth and invasive ability of BGC-823 cells more effectively than the combination of free drugs or P/T-NPs. In vivo study validated the therapeutic potential of P/T-NPs-Gelatin. P/T-NPs-Gelatin significantly inhibited the activation of p-Akt and the downstream anti-apoptotic Bcl-2 protein and also inducing the activation of pro-apoptotic Bax protein. Moreover, the molecular-modulating effect of P/T-NPs-Gelatin on related proteins varied slightly under the influence of NAC, which was supported by the observations of the tumor volumes and weights. Based on these findings, local implantation of P/T-NPs-Gelatin may be a promising therapeutic strategy for the treatment of gastric cancer.
authors.affiliation: Department of Geriatrics, the First Affiliated Hospital to Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, Jiangsu Taizhou People's Hospital, Taizhou, 225300, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China.|Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore, 117585.
authors.forename: Zhenshu
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Pharmacy, the First Affiliated Hospital to Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Huae
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Geriatrics, the First Affiliated Hospital to Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Nephrology, Huai'an Hospital Affiliated with Xuzhou Medical College and Huai'an Second Hospital, Huai'an 223002, China.
authors.forename: Donghui
authors.initials: D
authors.lastname: Zheng
authors.affiliation: Department of Geriatrics, the First Affiliated Hospital to Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Weihao
authors.initials: W
authors.lastname: Sun
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000494:pharmacology; D044182:Benzylisoquinolines / Q000008:administration & dosage* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D004357:Drug Synergism; D005780:Gelatin / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020100:Hydrogels / Q000737:chemistry; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D017239:Paclitaxel / Q000008:administration & dosage* / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C000595707:BCL2 protein, human; D044182:Benzylisoquinolines; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D019253:Proto-Oncogene Proteins c-bcl-2; C009438:tetrandrine; D005780:Gelatin; D051057:Proto-Oncogene Proteins c-akt; D017239:Paclitaxel