Dataset Information

Novel Hydrophilic Copolymer-Based Nanoparticle Enhances the Therapeutic Efficiency of Doxorubicin in Cultured MCF-7 Cells.

ABSTRACT: Nanoparticle drug delivery applications have predominantly focused on the entrapment and delivery of hydrophobic molecules with poor water solubility. However, benefits can also be obtained from nanoparticle-based delivery of hydrophilic therapeutics. This study reports on the development of a p(HEMA-ran-GMA)-based nanoparticle synthesized via a spontaneous water-in-oil inverse nanoemulsion to deliver doxorubicin, a water-soluble chemotherapeutic. High drug loading efficiency and sustained release of doxorubicin from Cy5-functionalized p(HEMA-ran-GMA) nanoparticles enabled effective inhibition of the MCF-7 human breast cancer derived cell line. Direct comparative analyses with a hydrophobic PGMA nanoparticle demonstrated enhanced capabilities of the p(HEMA-ran-GMA)-based nanoparticle in vitro. The results suggest that p(HEMA-ran-GMA)-based nanoparticles, which are better suited for hydrophilic drug loading and delivery, may have the potential for the improved therapeutic effect in vivo by enhanced permeation and retention of the nanoparticles by avoidance of off-site side effects of the chemotherapeutic.

SUBMITTER: Naidu PSR

PROVIDER: S-EPMC6811859 | biostudies-other | 2019 Oct

REPOSITORIES: biostudies-other

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Novel Hydrophilic Copolymer-Based Nanoparticle Enhances the Therapeutic Efficiency of Doxorubicin in Cultured MCF-7 Cells.

Naidu Priya S R PSR Norret Marck M Dunlop Sarah A SA Fitzgerald Melinda M Clemons Tristan D TD Iyer K Swaminathan KS

ACS omega 20191011 17

Nanoparticle drug delivery applications have predominantly focused on the entrapment and delivery of hydrophobic molecules with poor water solubility. However, benefits can also be obtained from nanoparticle-based delivery of hydrophilic therapeutics. This study reports on the development of a p(HEMA-<i>ran</i>-GMA)-based nanoparticle synthesized via a spontaneous water-in-oil inverse nanoemulsion to deliver doxorubicin, a water-soluble chemotherapeutic. High drug loading efficiency and sustaine ...[more]

PMID: 31656880

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Project description:Hepatocellular carcinoma (HCC) is an invasive malignant neoplasm with a poor prognosis. The development of chemoresistance severely obstructs the chemotherapeutic efficiency of HCC treatment. Therefore, understanding the mechanisms of chemoresistance is important for improving the outcomes of patients with HCC. Eukaryotic translation initiation factor 5A2 (eIF5A2), which is considered to be an oncogene, has been reported to mediate chemoresistance in various types of cancer; however, its precise role in HCC remains unclear. Accumulating evidence has suggested that autophagy serves a dual role in cancer chemotherapy. The present study aimed to investigate the role of autophagy in eIF5A2‑mediated doxorubicin resistance in HCC. High expression levels of eIF5A2 in human HCC tissues were observed by immunohistochemistry using a tissue microarray, which was consistent with the results of reverse transcription‑quantitative PCR analysis in paired HCC and adjacent healthy tissues. HCC patient‑derived tumor xenograft mouse model was used for the in vivo study, and knockdown of eIF5A2 effectively enhanced the efficacy of doxorubicin chemotherapy compared with that in the control group. Notably, eIF5A2 served as a repressor in regulating autophagy under chemotherapy. Silencing of eIF5A2 induced doxorubicin sensitivity in HCC cells by triggering lethal autophagy. In addition, 5‑ethynyl‑2'‑deoxyuridine, lactate dehydrogenase release assay and calcein‑AM/PI staining were used to determine the enhanced autophagic cell death induced by the silencing of eIF5A2 under doxorubicin treatment. Suppression of autophagy attenuated the sensitivity of HCC cells to doxorubicin induced by eIF5A2 silencing. The results also demonstrated that knockdown of the Beclin 1 gene, which is an autophagy regulator, reversed the enhanced autophagic cell death and doxorubicin sensitivity induced by eIF5A2 silencing. Taken together, these results suggested eIF5A2 may mediate the chemoresistance of HCC cells by suppressing autophagic cell death under chemotherapy through a Beclin 1‑dependent pathway, and that eIF5A2 may be a novel potential therapeutic target for HCC treatment.

Dataset Information

Novel Hydrophilic Copolymer-Based Nanoparticle Enhances the Therapeutic Efficiency of Doxorubicin in Cultured MCF-7 Cells.

Publications

Novel Hydrophilic Copolymer-Based Nanoparticle Enhances the Therapeutic Efficiency of Doxorubicin in Cultured MCF-7 Cells.

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