95611-10-2Relevant academic research and scientific papers
Gemcitabine loaded microbubbles for targeted chemo-sonodynamic therapy of pancreatic cancer
Nesbitt, Heather,Sheng, Yingjie,Kamila, Sukanta,Logan, Keiran,Thomas, Keith,Callan, Bridgeen,Taylor, Mark A.,Love, Mark,O'Rourke, Declan,Kelly, Paul,Beguin, Estelle,Stride, Eleanor,McHale, Anthony P.,Callan, John F.
, p. 8 - 16 (2018)
Pancreatic cancer remains one of the most lethal forms of cancer with a 10-year survival of a significant need for new treatments or more effective strategies to deliver existing treatments. The antimetabolite gemcitabine (Gem) is the most widely used form of chemotherapy for pancreatic cancer treatment, but is known to produce significant side effects when administered systemically. We have previously demonstrated the benefit of combined chemo-sonodynamic therapy (SDT), delivered using oxygen carrying microbubbles (O2MB), as a targeted treatment for pancreatic cancer in a murine model of the disease. In this manuscript, we report the preparation of a biotin functionalised Gem ligand for attachment to O2MBs (O2MB-Gem). We demonstrate the effectiveness of chemo-sonodynamic therapy following ultrasound-targeted-microbubble-destruction (UTMD) of the O2MB-Gem and a Rose Bengal loaded O2MB (O2MB-RB) as a targeted treatment for pancreatic cancer. Specifically, UTMD using the O2MB-Gem and O2MB-RB conjugates reduced the viability of MIA PaCa-2, PANC-1, BxPC3 and T110299 pancreatic cancer cells by >60% (p 80%, p 2MB-Gem conjugate was also determined in healthy non-tumour bearing MF1 mice and revealed no evidence of renal or hepatic damage. Therefore, the results presented in this manuscript suggest that chemo-sonodynamic therapy using the O2MB-Gem and O2MB-RB conjugates, is potentially an effective targeted and safe treatment modality for pancreatic cancer.
SONODYNAMIC THERAPY
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Page/Page column 44-45, (2019/01/04)
The invention relates to microbubble complexes for use in methods of sonodynamic therapy which comprise a microbubble attached to or otherwise associated with one or more linking groups, each linking group being bound to at least one sonosensitising agent and at least one chemotherapeutic agent. It further relates to the microbubble complexes themselves and to pharmaceutical compositions which contain them. The invention is particularly suitable for the treatment of deep-sited tumors, in particular pancreatic cancer.
Detection of protein S-sulfhydration by a tag-switch technique
Zhang, Dehui,MacInkovic, Igor,Devarie-Baez, Nelmi O.,Pan, Jia,Park, Chung-Min,Carroll, Kate S.,Filipovic, Milos R.,Xian, Ming
, p. 575 - 581 (2014/01/23)
Protein S-sulfhydration (forming -S-SH adducts from cysteine residues) is a newly defined oxidative posttranslational modification and plays an important role in H2S-mediated signaling pathways. In this study we report the first selective, tag-switch method which can directly label protein S-sulfhydrated residues by forming stable thioether conjugates. Furthermore we demonstrate that H2S alone cannot lead to S-sulfhydration and that the two possible physiological mechanisms include reaction with protein sulfenic acids (P-SOH) or the involvement of metal centers which would facilitate the oxidation of H2S to HS.. Selective detection: The first selective tag-switch method can be used to directly label protein persulfide units (sites of S-sulfhydration) in the form of stable thioether conjugates. It is thought that H2S alone cannot lead to S-sulfhydration and that the two possible physiological mechanisms include reaction with protein sulfenic acids (P-SOH) and the involvement of metal centers, which would facilitate the oxidation of H2S to HS..
Transporter-targeted lipid prodrugs of cyclic cidofovir: A potential approach for the treatment of cytomegalovirus retinitis
Gokulgandhi, Mitan R.,Barot, Megha,Bagui, Mahuya,Pal, Dhananjay,Mitra, Ashim K.
experimental part, p. 3249 - 3263 (2012/09/08)
Cidofovir (CDF) and its cyclic analogue (cCDF) have shown potential in vitro and in vivo antiviral activity against cytomegalovirus (CMV) retinitis. However, hydrophilic nature of CDF may affect cell permeation across lipophilic epithelium and thus limit its effectiveness in the treatment of CMV retinitis. In the present study, we have tested a novel hypothesis, which involves chemical derivatization of cCDF into lipophilic transporter-targeted prodrug [via conjugation with different carbon chain length of lipid raft and targeting moiety (biotin) for sodium-dependent multivitamin transporter (SMVT)]. We have synthesized and characterized three derivatives of cCDF including biotin B-C2-cCDF, B-C6-cCDF, and B-C12-cCDF. Physicochemical properties such as solubility, partition coefficient (n-octanol/water and ocular tissue), bioreversion kinetics, and interaction with SMVT transporter have been determined. Among these novel conjugates, B-C12-cCDF has shown higher interaction to SMVT transporter with lowest half maximal inhibitory concentration value, higher cellular accumulation, and high tissue partitioning. Improvement in physicochemical properties, lipophilicity, and interaction with transporter was observed in the trend of increasing the lipid chain length, that is, B-C12-cCDF > B-C6-cCDF > B-C2-cCDF. These results indicate that transporter-targeted lipid analogue of cCDF exhibits improved cellular accumulation along with higher transporter affinity and hence could be a viable strategy for the treatment of CMV retinitis.
Synthesis of 18F-labelled biotin analogues
Blom, Elisabeth,Itsenko, Oleksiy,Langstroem, Bengt
scheme or table, p. 681 - 683 (2012/01/13)
A one-step 18F-labelling strategy was used to prepare three labelled analogues of the vitamin biotin, which can be useful as tracers because of biotin's high affinity for avidin. The labelled compounds were obtained in decay-corrected yields of up to 35% and specific radioactivity of 320 GBq/μmol. When evaluated in situ, the analogues showed good affinity for avidin: 60-75% of the radiolabelled compounds were bound to avidin within 5 minutes. The binding was site-specific, as shown by blocking experiments with native biotin. Copyright
