Dataset Information

Delivery of Doxorubicin for Human Cervical Carcinoma Targeting Therapy by Folic Acid-Modified Selenium Nanoparticles.

ABSTRACT: Cancer-specific drug delivery represents an attractive approach to preventing undesirable side effects and increasing the accumulation of the drug in tumors. The surface modification of selenium nanoparticles (SeNPs) with targeting moieties thus represents an effective strategy for cancer therapy. In this study, SeNPs were modified with folic acid (FA), whose receptors were overexpressed on the surface of cancer cells, including human cervical carcinoma HeLa cells, to fabricate tumor-targeting delivery carrier FA-SeNPs nanoparticles. Then, the anticancer drug doxorubicin (DOX) was loaded onto the surface of the FA-SeNPs for improving the antitumor efficacy of DOX in human cervical carcinoma therapy. The chemical structure characterization of FA-Se@DOX showed that DOX was successfully loaded to the surface of FA-SeNPs to prepare FA-Se@DOX nanoparticles. FA-Se@DOX exhibited significant cellular uptake in human cervical carcinoma HeLa cells (folate receptor overexpressing cells) in comparison with lung cancer A549 cells (folate receptor deficiency cells), and entered HeLa cells mainly by the clathrin-mediated endocytosis pathway. Compared to free DOX or Se@DOX at the equivalent dose of DOX, FA-Se@DOX showed obvious activity to inhibit HeLa cells' proliferation and induce the apoptosis of HeLa cells. More importantly, FA-Se@DOX could specifically accumulate in the tumor site, which contributed to the significant antitumor efficacy of FA-Se@DOX in vivo. Taken together, FA-Se@DOX may be one novel promising drug candidate for human cervical carcinoma therapy.

SUBMITTER: Xia Y

PROVIDER: S-EPMC6274826 | biostudies-other | 2018 Nov

REPOSITORIES: biostudies-other

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Delivery of Doxorubicin for Human Cervical Carcinoma Targeting Therapy by Folic Acid-Modified Selenium Nanoparticles.

Xia Yu Y Xu Tiantian T Zhao Mingqi M Hua Liang L Chen Yi Y Wang Changbing C Tang Ying Y Zhu Bing B

International journal of molecular sciences 20181113 11

Cancer-specific drug delivery represents an attractive approach to preventing undesirable side effects and increasing the accumulation of the drug in tumors. The surface modification of selenium nanoparticles (SeNPs) with targeting moieties thus represents an effective strategy for cancer therapy. In this study, SeNPs were modified with folic acid (FA), whose receptors were overexpressed on the surface of cancer cells, including human cervical carcinoma HeLa cells, to fabricate tumor-targeting d ...[more]

PMID: 30428576

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Project description:This study concerns the development of folic acid (FA)-functionalized iron oxide condensed colloidal magnetic clusters for a more selective delivery of doxorubicin (DOX) to tumor cancer cells overexpressing the folate receptor. Alginate-coated condensed magnetic nanoparticles (co-MIONs) were synthesized via an alkaline precipitation method of an iron precursor in the presence of sodium alginate. Poly(ethylene glycol) (OH-PEG-NH2) was conjugated to the carboxylic acid end group of alginate and folic acid (FA) was conjugated to the hydroxyl terminal group of PEG to produce folate-functionalized, pegylated co-MIONS (Mag-Alg-PEG-FA). The physicochemical properties of nanoparticles were fully characterized. DOX was loaded on the nanoparticles, and the cellular uptake and anticancer efficacy of the nanoparticles were examined in cancer cell lines expressing and not expressing the folate receptor. The biocompatibility of the carrier (blank nanoparticles) was also evaluated by cytocompatibility and hemocompatibility experiments. The nanoparticles exhibited sustained DOX release in aqueous buffers and biorelevant media, which was responsive to pH and external alternating current magnetic fields. The effect of the magnetic field on DOX percentage release appeared to be independent of the timing (onset time) of magnetic field application, providing flexibility to the magnetic control of drug release from the nanoparticles. The blank nanoparticles were not cytotoxic and did not cause hemolysis. The DOX-loaded and FA-functionalized nanoparticles exhibited increased uptake and caused increased apoptosis and cytotoxicity against the MDA-MB-231 cell line, expressing the folate receptor, compared to the MCF-7 cell line, not expressing the folate receptor. The application of a 0.5 T magnetic field during incubation of the nanoparticles with the cancer cells increased the cellular uptake and cytotoxicity of the nanoparticles. The obtained results indicate the potential of the folate-functionalized, pegylated co-MIONS for a more efficacious DOX delivery to cancer cells of solid tumors.

Project description:Doxorubicin (DOX) is one of the most commonly used antineoplastic agents, but its clinical application is oftentimes coupled with severe side effects. Selective delivery of DOX to tumors via nanosized drug carrier represents an attractive approach to this problem. Previously, we developed a dual functional nanomicellar carrier, PEG5K-embelin2 (PEG5K-EB2), which was able to deliver paclitaxel (PTX) selectively to tumors and to achieve an enhanced therapeutic effect. In the present study, we examined the utility of PEG5K-EB2 to deliver DOX to tumors. In addition, folic acid (FA) was coupled to the surface of the PEG5K-EB2 micelles (FA-PEG5K-EB2) to further improve the selective targetability of the system. DOX-loaded PEG5K-EB2 micelles were uniformly spherical particles with a diameter of approximately 20 nm. Incorporation of FA had minimal effect on the size of the particles. The DOX loading efficiency was as high as 91.7% and 93.5% for PEG5K-EB2 and FA-PEG5K-EB2, respectively. DOX formulated in PEG5K-EB2 micelles (with or without FA decoration) demonstrated sustained kinetics of DOX release compared to free DOX. FA-PEG5K-EB2 significantly facilitated the intracellular uptake of DOX over free DOX and PEGylated liposomal DOX (Doxil) in breast cancer cells, 4T1.2, and drug resistant cells, NCI/ADR-RES. P-gp ATPase assay showed that PEG5K-EB2 significantly inhibited the function of the P-gp efflux pump. The maximum tolerated dose of DOX-loaded PEG5K-EB2 micelles was 15 mg/kg in mice, which was 1.5-fold greater than that for free DOX. Pharmacokinetics (PK) and biodistribution studies showed that both types of DOX-loaded micelles, especially FA-PEG5K-EB2, were able to significantly prolong the blood circulation time of DOX and facilitate its preferential accumulation at the tumor tissue. Finally, DOX/PEG5K-EB2 mixed micelles demonstrated significantly enhanced tumor growth inhibitory effect with minimal toxicity in comparison to free DOX and Doxil and the antitumor activity was further enhanced after the decoration by folic acid. Our data suggest that FA-PEG5K-EB2 micelles represent a promising DOX delivery system that warrants more study in the future.

Dataset Information

Delivery of Doxorubicin for Human Cervical Carcinoma Targeting Therapy by Folic Acid-Modified Selenium Nanoparticles.

Publications

Delivery of Doxorubicin for Human Cervical Carcinoma Targeting Therapy by Folic Acid-Modified Selenium Nanoparticles.

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