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- 저자 : Manganiello, Vincent (검색결과 3 건)
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Bifunctional Tumor-Targeted Bioprobe for Phothotheranosis
Hae Sang Park,Shinya Yokomizo,Haoran Wang,Sophia Manganiello,Hailey Monaco,Rose McDonnell,Hajin Joanne Kim,Jiyun Rho,Sung Ahn,정해리,강호만,Kai Bao,Satoshi Kashiwagi,Hak Soo Choi 한국생체재료학회 2024 생체재료학회지 Vol.28 No.00
Background: Near-infrared (NIR) phototheranostics provide promising noninvasive imaging and treatment for head and neck squamous cell carcinoma (HNSCC), capitalizing on its adjacency to skin or mucosal surfaces. Activated by laser irradiation, targeted NIR fluorophores can selectively eradicate cancer cells, harnessing the power of synergistic photodynamic therapy and photothermal therapy. However, there is a paucity of NIR bioprobes showing tumor-specific targeting and effective phototheranosis without hurting surrounding healthy tissues. Methods: We engineered a tumor-specific bifunctional NIR bioprobe designed to precisely target HNSCC and induce phototheranosis using bioconjugation of a cyclic arginine–glycine–aspartic acid (cRGD) motif and zwitterionic polymethine NIR fluorophore. The cytotoxic effects of cRGD-ZW800-PEG were measured by assessing heat and reactive oxygen species (ROS) generation upon an 808-nm laser irradiation. We then determined the in vivo efficacy of cRGD-ZW800-PEG in the FaDu xenograft mouse model of HNSCC, as well as its biodistribution and clearance, using a customized portable NIR imaging system. Results: Real-time NIR imaging revealed that intravenously administered cRGD-ZW800-PEG targeted tumors rapidly within 4 h postintravenous injection in tumor-bearing mice. Upon laser irradiation, cRGD-ZW800-PEG produced ROS and heat simultaneously and exhibited synergistic photothermal and photodynamic effects on the tumoral tissue without affecting the neighboring healthy tissues. Importantly, all unbound bioprobes were cleared through renal excretion. Conclusions: By harnessing phototheranosis in combination with tailored tumor selectivity, our targeted bioprobe ushers in a promising paradigm in cancer treatment. It promises safer and more efficacious therapeutic avenues against cancer, marking a substantial advancement in the field.
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SFPQ, a multifunctional nuclear protein, regulates the transcription of <i>PDE3A</i>
Rhee, Dong ,Keun,Hockman, Steven ,C.,Choi, Sunkyung,Kim, Yong-Eun,Park, Chungoo,Manganiello, Vincent ,C.,Kim, Kee ,K. Portland Press Ltd. 2017 Bioscience reports Vol.37 No.4
<P>Phosphodiesterase 3A (PDE3A), a member of the cGMP-inhibited cyclic nucleotide phosphodiesterase (PDE) family, plays important roles in oocyte maturation and vascular smooth muscle cell proliferation. However, the molecular mechanisms that regulate <I>PDE3A</I> gene expression remain largely unknown. In the present study, we investigated the transcriptional regulation of <I>PDE3A</I>, and found that the splicing factor proline- and glutamine-rich (SFPQ) protein modulated <I>PDE3A</I> mRNA levels. Multiple transcription start sites (TSS1, 2, and 3) were identified within the first exon of <I>PDE3A</I> using 5′-rapid amplification of cDNA ends (RACE). Variable expression levels of three <I>PDE3A</I> variants were also observed in human tissues and HeLa cells. Several putative SFPQ-binding sites were identified upstream of the regulatory region of <I>PDE3A</I>-TSSs using ChIP sequencing (ChIP-seq). Serum-induced <I>PDE3A</I> expression was affected by increasing the amount of SFPQ binding to the upstream regulatory region of <I>PDE3A</I>. In addition, transcription of <I>PDE3A</I> was lower in human cervical adenocarcinoma cells compared with normal cervical tissue. Furthermore, overexpression of <I>PDE3A</I> induced sensitivity to anticancer therapeutic agent, 6-(4-(diethylamino)-3-nitrophenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one (DNMDP), in HeLa cells. Taken together, these results suggest that SFPQ functions as a transcriptional activator of <I>PDE3A</I>, which is involved in the regulation of DNMDP sensitivity, offering a novel molecular target for the development of anticancer therapies.</P>
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