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Ultrahigh affinity Raman probe for targeted live cell imaging of prostate cancer.

ABSTRACT: Precise visualization of tumor margins with characterization of microscopic tumor invasion are unmet needs in prostate oncology that demand approaches with high sensitivity and specificity. To address those needs we report surface-enhanced Raman scattering (SERS) based optical imaging for prostate cancer using a combination of live cell Raman microscopy, optimally engineered SERS tags and a urea-based small-molecule inhibitor of prostate-specific membrane antigen (PSMA) as a targeting moiety. We develop gold nanostar based SERS agents that offer ultrahigh binding affinity to PSMA with nearly four orders of magnitude lower IC₅₀ values in relation to existing clinical imaging agents. This combination enables selective recognition of prostate cancer cells, and facilitates quantitative and photostable Raman measurements. Using Raman microscopy to analyze phenotypically similar prostate cancer cell lines differing only in PSMA expression, we demonstrate facile, site-selective recognition using as low as 20 pM of the SERS agent for imaging, opening the door for spectroscopic detection of prostate and other PSMA-expressing tumors in vivo.

SUBMITTER: Li M

PROVIDER: S-EPMC5356002 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Ultrahigh affinity Raman probe for targeted live cell imaging of prostate cancer.

Li Ming M Banerjee Sangeeta Ray SR Zheng Chao C Pomper Martin G MG Barman Ishan I

Chemical science 20160715 11

Precise visualization of tumor margins with characterization of microscopic tumor invasion are unmet needs in prostate oncology that demand approaches with high sensitivity and specificity. To address those needs we report surface-enhanced Raman scattering (SERS) based optical imaging for prostate cancer using a combination of live cell Raman microscopy, optimally engineered SERS tags and a urea-based small-molecule inhibitor of prostate-specific membrane antigen (PSMA) as a targeting moiety. We ...[more]

PMID: 28451123

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Project description:Androgen deprivation therapy (ADT) is the standard of care for high risk and advanced prostate cancer; however, disease progression from androgen-dependent prostate cancer (ADPC) to lethal and incurable castration-resistant prostate cancer (CRPC) and (in a substantial minority of cases) neuroendocrine prostate cancer (NEPC) is common. Identifying effective targeted therapies is challenging because of acquired resistance to established treatments and the vast heterogeneity of advanced prostate cancer (PC). To streamline the identification of potentially active prostate cancer therapeutics, we have developed an adaptable semi-automated protocol which optimizes cell growth and leverages automation to enhance robustness, reproducibility, and throughput while integrating live-cell imaging and endpoint viability assays to assess drug efficacy in vitro. In this study, culture conditions for 72-hr drug screens in 96-well plates were established for a large, representative panel of human prostate cell lines including: BPH-1 and RWPE-1 (non-tumorigenic), LNCaP and VCaP (ADPC), C4-2B and 22Rv1 (CRPC), DU 145 and PC3 (androgen receptor-null CRPC), and NCI-H660 (NEPC). The cell growth and 72-hr confluence for each cell line was optimized for real-time imaging and endpoint viability assays prior to screening for novel or repurposed drugs as proof of protocol validity. We demonstrated effectiveness and reliability of this pipeline through validation of the established finding that the first-in-class BET and CBP/p300 dual inhibitor EP-31670 is an effective compound in reducing ADPC and CRPC cell growth. In addition, we found that insulin-like growth factor-1 receptor (IGF-1R) inhibitor linsitinib is a potential pharmacological agent against highly lethal and drug-resistant NEPC NCI-H660 cells. This protocol can be employed across other cancer types and represents an adaptable strategy to optimize assay-specific cell growth conditions and simultaneously assess drug efficacy across multiple cell lines.

Dataset Information

Ultrahigh affinity Raman probe for targeted live cell imaging of prostate cancer.

Publications

Ultrahigh affinity Raman probe for targeted live cell imaging of prostate cancer.

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