title: Integrin α(V)β(3)-targeted magnetic nanohybrids with enhanced antitumor efficacy, cell cycle arrest ability, and encouraging anti-cell-migration activity.
abstract: Organic/inorganic nanohybrids, which integrate advantages of the biocompatibility of organic polymers and diversified functionalities of inorganic nanoparticles, have been extensively investigated in recent years. Herein, we report the construction of arginine-glycine-aspartic acid-cysteine (RGDC) tetrapeptide functionalized and 10-hydroxycamptothecin (HCPT)-encapsulated magnetic nanohybrids (RFHEMNs) for integrin αVβ3-targeted drug delivery. The obtained RFHEMNs were near-spherical in shape with a homogeneous size about 50 nm, and exhibited a superparamagnetic behavior. In vitro drug release study showed a sustained and pH-dependent release profile. Cell viability tests revealed that RFHEMNs displayed a significant enhancement of cytotoxicity against αVβ3-overexpressing A549 cells, as compared to free HCPT and nontargeting micelles. Flow cytometry analysis indicated that this cytotoxic effect was associated with dose-dependent S phase arrest. Finally, RFHEMNs exerted encouraging anti-cell-migration activity as determined by an in vitro wound-healing assay and a transwell assay. Overall, we envision that this tumor-targeting nanoscale drug delivery system may be of great application potential in chemotherapy of primary tumor and their metastases.
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, College of Life Science, and §National Engineering Laboratory for AIDS Vaccine, Jilin University , Changchun 130012, People's Republic of China.
authors.forename: Guo-Bin
authors.initials: GB
authors.lastname: Ding
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Guo
authors.forename: Li
authors.initials: L
authors.lastname: Xu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000494:pharmacology; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D065546:Drug Liberation; D057809:HEK293 Cells; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D019344:Lactic Acid / Q000737:chemistry; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D008301:Maleimides / Q000737:chemistry; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D010455:Peptides / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D066244:Proton Magnetic Resonance Spectroscopy; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D039302:Integrin alphaVbeta3; D058185:Magnetite Nanoparticles; D008301:Maleimides; D008823:Micelles; D010455:Peptides; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; C043592:maleimide; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol; C028098:10-hydroxycamptothecin; D002166:Camptothecin
keywords: RGDC tetrapeptide; anti-cell-migration; antitumor efficacy; cell cycle; integrin targeting; magnetic nanohybrids