期刊
JOURNAL OF BIOMEDICAL NANOTECHNOLOGY
卷 12, 期 8, 页码 1688-1698出版社
AMER SCIENTIFIC PUBLISHERS
DOI: 10.1166/jbn.2016.2278
关键词
Nanoparticles; pH-Sensitive; Polymeric Micelles; Carboxymethyl Chitosan; Daunorubicin
资金
- National Natural Science Foundation of China [51273156, 51373130, 31300791]
- Natural Science Foundation of Hubei Province [2014CFB877]
- Crohn's and Colitis Foundation of America (CCFA) Career Award [348137]
- Iowa State University (ISU) President's Initiative on Interdisciplinary Research (PIIR) program
- McGee-Wagner Interdisciplinary Research Award
Nanoparticles, such as polymeric micelles, are currently regarded as effective drug delivery vehicles. In this study, a series of carboxymethyl chitosan/daunorubicin (CMCS/DNR) conjugates with macromolecular carriers of different molecular weights (MWs) were prepared and structurally characterized by Fourier transform infrared spectroscopy (FT-IR) and H-1-NMR spectroscopy. The results indicated that the MWs of the carriers greatly influenced the drug loading capacity. DNR was conjugated to the polymer via an acid-sensitive hydrazone linkage susceptible to hydrolysis at pH 5-6, thereby enabling intracellular DNR release. In aqueous media, the conjugates spontaneously formed nano-sized particles with core-shell structures (CMCS and DNR as the shell and core, respectively). Dynamic light scattering (DLS) and transmission electron microscopy (TEM) indicated that the prepared nanoparticles were spherical in shape with diameters of 100-200 nm and had a slight negative surface charge. In addition, in vitro drug release studies demonstrated that the micelles were highly sensitive to mild acidic conditions (pH 5.0) but remained reasonably stable at pH 6.5 and pH 7.4. Importantly, cell counting kit-8 (CCK-8) assays demonstrated that DNR-conjugated nanoparticles exerted a cytotoxic effect on HeLa cells, with the IC50 being approximately 2 times higher than that of free-DNR. Furthermore, confocal laser scanning microscopy (CLSM) revealed that the CMCS-hyd-DNR nanosystem could efficiently deliver and release DNR in the nuclei of cancer cells. Taken together, the developed CMCS based pH-sensitive nanosystem may be a potential drug delivery vehicle for cancer therapy.
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