Second-generation aptamer-conjugated PSMA-targeted delivery system for prostate cancer therapy

Wu, Xin; Ding, Baoyue; Gao, Jing; Wang, Huanyun; Fan, Wei; Wang, Xiang; Zhang, Wei; Wang, Xiaoyu; Ye, Lihua; Zhang, Min; Ding, Xueying; Liu, Jiyong; Zhu, Quangang; Gao, Shen

doi:10.2147/ijn.s23747

Cited by 48 publications

(11 citation statements)

References 32 publications

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“…Prostate specific antigen (PSA) is a well-established biomarker that is expressed and released from LNCaP cells [ 35 ]. miR-16 the epithelial marker, expressed in these cells [ 36 ] together with widely expressed nucleotide markers, miR-141 and miR-200c were studied. The cells were studied at the varying ultrasound intensities as was done for the LS174T cell line.…”

Section: Resultsmentioning

confidence: 99%

Tumor characterization by ultrasound-release of multiple protein and microRNA biomarkers, preclinical and clinical evidence

et al. 2018

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We have previously shown that low frequency ultrasound can release biomarkers from cells into the murine circulation enabling an amplification and localization of the released biomarker that could be used as a blood-based method to detect cancer earlier and monitor therapy. In this study, we further demonstrate that this technique could be used for characterization of tumors and/or identification of cellular masses of unknown origin due to the release of multiple protein and nucleic acid biomarkers in cells in culture, mice and patients. We sonicated colon (LS174T) and prostate (LNCaP) cancer cell lines in culture at a low frequency of 1 MHz and show that there were several-fold changes in multiple protein and microRNA (miRNA) abundance with treatment at various intensities and time. This release was dependent on the duration and intensity of the sonication for both cell lines. Significant increased release in biomarkers was also observed following tumor sonication in living mice bearing subcutaneous LS174T cell line xenografts (for proteins and nucleic acids) and in an experimental LS174T liver tumor model (for proteins only). Finally, we demonstrated this methodology of multiple biomarker release in patients undergoing ablation of uterine fibroids using MR guided high intensity focused ultrasound. Two protein biomarkers significantly increased in the plasma after the ultrasound treatment in 21 samples tested. This proof that ultrasound-amplification method works in soft tissue tumor models together with biomarker multiplexing, could allow for an effective non-invasive method for identification, characterization and localization of incidental lesions, cancer and other disease. Pre-treatment quantification of the biomarkers, allows for individualization of quantitative comparisons. This individualization of normal marker levels in this method allows for specificity of the biomarker-increase to each patient, tumor or organ being studied.

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Section: Resultsmentioning

confidence: 99%

Tumor characterization by ultrasound-release of multiple protein and microRNA biomarkers, preclinical and clinical evidence

et al. 2018

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“…123 In this design, negatively charged miR-15a and miR-16-1 were complexed with PAMAM dendrimers through an electrostatic interaction. PEG served as a spacer to separate the positively charged dendrimer from the aptamers, reducing the interference with the active folding of aptamers.…”

Section: Cell-specific Aptamer-functionalized Agentsmentioning

confidence: 99%

Cell-type-specific, Aptamer-functionalized Agents for Targeted Disease Therapy

Zhou

Rossi

2014

Molecular Therapy - Nucleic Acids

210

162

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One hundred years ago, Dr. Paul Ehrlich popularized the “magic bullet” concept for cancer therapy in which an ideal therapeutic agent would only kill the specific tumor cells it targeted. Since then, “targeted therapy” that specifically targets the molecular defects responsible for a patient's condition has become a long-standing goal for treating human disease. However, safe and efficient drug delivery during the treatment of cancer and infectious disease remains a major challenge for clinical translation and the development of new therapies. The advent of SELEX technology has inspired many groundbreaking studies that successfully adapted cell-specific aptamers for targeted delivery of active drug substances in both in vitro and in vivo models. By covalently linking or physically functionalizing the cell-specific aptamers with therapeutic agents, such as siRNA, microRNA, chemotherapeutics or toxins, or delivery vehicles, such as organic or inorganic nanocarriers, the targeted cells and tissues can be specifically recognized and the therapeutic compounds internalized, thereby improving the local concentration of the drug and its therapeutic efficacy. Currently, many cell-type-specific aptamers have been developed that can target distinct diseases or tissues in a cell-type-specific manner. In this review, we discuss recent advances in the use of cell-specific aptamers for targeted disease therapy, as well as conjugation strategies and challenges.

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“…In addition, nucleic acid as a targeted probe can avoid immunogenicity, and its high purity makes it safer than other ligands (Dougherty et al 2015 ; Alibolandi et al 2015 ; Lee et al 2011 ). Early aptamers A10 and A9 were selected from the synthetic RNA aptamer sequences and effectively connected to the PSMA (Rockey et al 2011 ; Wu et al 2011 ). However, they are composed of 79 nucleotides.…”

Section: Introductionmentioning

confidence: 99%

Aptamer-conjugated multi-walled carbon nanotubes as a new targeted ultrasound contrast agent for the diagnosis of prostate cancer

Xia

et al. 2018

J Nanopart Res

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Early diagnosis is primarily important for the therapeutic and prognostic outcomes of malignancies including prostate cancer (PCa). However, the visuality and veracity of ultrasound imaging for the diagnosis and prognostic prediction of PCa remains poor at present. In this study, we developed a new nanoultrasound contrast agent by modifying multi-walled carbon nanotubes (MWCNTs) with polyethylene glycol (PEG) and anti-PSMA aptamer. The result showed that the modified MWCNTs offered better visuality and veracity and were able to target PCa cells more effectively as compared with the traditional contrast agent. The zeta potential was about − 38 mv. The length of this contrast agent was about 400 nm and the diameter of it was about 30 nm. The zeta potential, TEM, and FT-IR all proved the successful preparation of the agent. The vitro cytological study revealed good cell uptake and biocompatibility of the new contrast agent. The minimum detection concentration in vitro is 10 μg/ml. The earliest stage of the detection was under the parameters of frequency = 6.0 MHz and medical index = 0.06. Both in vitro and in vivo ultrasound imaging demonstrated that the new nanoultrasound contrast agent had a good development effect, distribution, and metabolism, and may prove to be a good targeted ultrasound contrast agent, especially for PCa.

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Second-generation aptamer-conjugated PSMA-targeted delivery system for prostate cancer therapy

Cited by 48 publications

References 32 publications

Tumor characterization by ultrasound-release of multiple protein and microRNA biomarkers, preclinical and clinical evidence

Tumor characterization by ultrasound-release of multiple protein and microRNA biomarkers, preclinical and clinical evidence

Cell-type-specific, Aptamer-functionalized Agents for Targeted Disease Therapy

Aptamer-conjugated multi-walled carbon nanotubes as a new targeted ultrasound contrast agent for the diagnosis of prostate cancer

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