Dataset Information

Phospholipase A2-Responsive Phosphate Micelle-Loaded UCNPs for Bioimaging of Prostate Cancer Cells.

ABSTRACT: We report the effective synthesis of biocompatible upconversion nanoparticles (UCNP)-loaded phosphate micelles and successful delivery of UCNPs to prostate cancer cells via secreted phospholipase A2 (sPLA-2) enzyme cleavage of the loaded micelles for the first time. The activity of the (sPLA-2) enzyme toward the synthesized micelles was investigated and confirmed by LC-MS. TEM results showed that the micelles have a size distribution of 80 to 150?nm, whereas UCNP-loaded micelles range from 200 to 350?nm, indicating the successful loading of UCNPs. The selective release of UCNPs to prostate cancer cells rather than other cells, specifically cervical cancer cells, was observed and confirmed by a range of bioimaging studies. Moreover, cytotoxicity assays confirmed the biocompatibility of the UCNP-loaded micelles.

SUBMITTER: Sharipov M

PROVIDER: S-EPMC5700164 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Phospholipase A2-Responsive Phosphate Micelle-Loaded UCNPs for Bioimaging of Prostate Cancer Cells.

Sharipov Mirkomil M Tawfik Salah M SM Gerelkhuu Zayakhuu Z Huy Bui The BT Lee Yong-Ill YI

Scientific reports 20171122 1

We report the effective synthesis of biocompatible upconversion nanoparticles (UCNP)-loaded phosphate micelles and successful delivery of UCNPs to prostate cancer cells via secreted phospholipase A2 (sPLA-2) enzyme cleavage of the loaded micelles for the first time. The activity of the (sPLA-2) enzyme toward the synthesized micelles was investigated and confirmed by LC-MS. TEM results showed that the micelles have a size distribution of 80 to 150 nm, whereas UCNP-loaded micelles range from 200 t ...[more]

PMID: 29167526

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Project description:Secretory phospholipase A(2) (sPLA(2)) cleave phospholipids at sn-2 ester bonds, releasing lysophospholipids and fatty acids, and are over expressed in several pathologies, including inflammation, arthritis, sepsis and breast and prostate cancers. Herein we evaluated the therapeutic activity of liposomes engineered to be responsive to different sPLA(2) isoforms compared to clinically used long-circulating (pegylated) sterically stabilized liposomes (SSL) in vitro and in vivo, and assessed differences in roles of sPLA(2) in the mechanism of uptake and delivery of these nanoparticles. Exposing sPLA(2) responsive liposomes (SPRL) to sPLA(2) increased the release of intraluminal entrapped contents in a time-dependent manner that was inhibited by the sPLA(2) inhibitor LY3117273. Treatment of prostate cancer cells with doxorubicin encapsulated in SSL and SPRL resulted in cytotoxicity in LNCaP, DU-145 and PC-3 cells lines comparable to free drug. Interestingly, cytotoxicity was not altered by sPLA(2) inhibition. Tracking of drug and liposome delivery using fluorescence microscopy and flow cytometry, we demonstrated that drug uptake was liposome-dependent, as encapsulation of doxorubicin in SPRL resulted in 1.5 to 2-fold greater intracellular drug levels compared to SSL. Liposome uptake was cell-dependent and did not correlate to doxorubicin uptake; however, doxorubicin uptake was generally greatest in PC-3 cells, followed by DU-145 cells and then LNCaP cells. In almost all cases, uptake of one of our formulations, SPRL-E, was greater than SSL. The therapeutic activity of SPRL in vivo was demonstrated using a mouse xenograft model of human prostate cancer, which showed that doxorubicin entrapped within SPRL decreased tumor growth compared to SSL, suggesting that SPRL are more effective at slowing tumor growth than a SSL formulation similar to the FDA approved DOXIL™. Collectively, these data show the therapeutic activity of SPRL compared to SSL, yield insights into the mechanisms of action of these nanoparticles and suggest that SPRL could be useful for treatment of other pathologies that over express sPLA(2).

Dataset Information

Phospholipase A2-Responsive Phosphate Micelle-Loaded UCNPs for Bioimaging of Prostate Cancer Cells.

Publications

Phospholipase A2-Responsive Phosphate Micelle-Loaded UCNPs for Bioimaging of Prostate Cancer Cells.

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