Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 6, Issue 19, Pages 16643-16652Publisher
AMER CHEMICAL SOC
DOI: 10.1021/am503359g
Keywords
RGDC tetrapeptide; integrin targeting; magnetic nanohybrids; antitumor efficacy; cell cycle; anti-cell migration
Funding
- National Natural Science Foundation of China [81271697]
- Specialized Research Fund for the Doctoral Program of Higher Education of China [20120061110021]
- Social Development Project of Science and Technology Department of Jilin Province, China [20106031, 20120967, YYZX201264, 20130206069GX]
- Fundamental Research Funds for the Central Universities, Significant New Drug Creation Science and Technology Major Program [2012ZX09503001-003]
- Science Foundation for Youths of Shanxi Province [2013021014-1]
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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 alpha(V)beta(3)-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 alpha(V)beta(3)-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.
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