title: Nanoparticles inhibit cancer cell invasion and enhance antitumor efficiency by targeted drug delivery via cell surface-related GRP78.
abstract: Nanoparticles (NPs) which target specific agents could effectively recognize the target cells and increase the stability of chemical agents by encapsulation. As such, NPs have been widely used in cancer treatment research. Recently, over 90% of treatment failure cases in patients with metastatic cancer were attributed to resistance to chemotherapy. Surface-exposed glucose-regulated protein of 78 kDa (GRP78) is expressed highly on many tumor cell surfaces in many human cancers and is related to the regulation of invasion and metastasis. Herein, we report that NPs conjugated with antibody against GRP78 (mAb GRP78-NPs) inhibit the adhesion, invasion, and metastasis of hepatocellular carcinoma (HCC) and promote drug delivery of 5-fluorouracil into GRP78 high-expressed human hepatocellular carcinoma cells. Our new findings suggest that mAb GRP78-NPs could enhance drug accumulation by effectively transporting NPs into cell surface GRP78-overexpressed human hepatocellular carcinoma cells and then inhibit cell proliferation and viability and induce cell apoptosis by regulating caspase-3. In brief, mAb GRP78-NPs effectively inhibit cancer cell invasion and enhance antitumor efficiency by targeted drug delivery.
authors.affiliation: School of Pharmacy, Liaoning Medical University, Jinzhou, People's Republic of China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Central Laboratory of Liaoning Medical University, Jinzhou, People's Republic of China.
authors.forename: Hongdan
authors.initials: H
authors.lastname: Li
authors.affiliation: School of Pharmacy, Liaoning Medical University, Jinzhou, People's Republic of China.
authors.forename: Yijie
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Central Laboratory of Liaoning Medical University, Jinzhou, People's Republic of China.
authors.forename: Guan
authors.initials: G
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Liaoning Medical University, Jinzhou, People's Republic of China.
authors.forename: Liwei
authors.initials: L
authors.lastname: Liu
authors.affiliation: School of Veterinary Medicine, Liaoning Medical University, Jinzhou, People's Republic of China.
authors.forename: Chang
authors.initials: C
authors.lastname: Su
authors.affiliation: Central Laboratory of Liaoning Medical University, Jinzhou, People's Republic of China.
authors.forename: Rongjian
authors.initials: R
authors.lastname: Su
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems; D000091342:Endoplasmic Reticulum Chaperone BiP; D005472:Fluorouracil / Q000737:chemistry / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy; D053758:Nanoparticles / Q000737:chemistry*; D009361:Neoplasm Invasiveness / Q000517:prevention & control*
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C505407:CASP3 protein, human; D053148:Caspase 3; D005472:Fluorouracil
keywords: 5-Fu; HCC; apoptosis; caspase-3