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      저자 : Sushil K. Dwivedi (검색결과 2 건)
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      • KCI등재

        Recent progress of enzyme cleavable linker in antibody–drug conjugates: sulfatase and phosphatase

        Sushil K. Dwivedi,Abhinav Bhise,Rajkumar Subramani,유정수 대한방사성의약품학회 2021 Journal of radiopharmaceuticals and molecular prob Vol.7 No.1

        Recently, antibody–drug conjugates (ADCs) are used to deliver efficient cytotoxic payloads selectively in cancer cells. In the designing of an ADC, the antibody is connected to a toxic payload via a covalent linker, which helps to solubilizes the typical hydrophobic payload as well as stabilizes the linkage over circulation. The development of the linkers for the antibody drug conjugate is still in demand. Initially, the acid, disulfide, and cathepsin-sensitive ADCs attracted considerable attention for the delivery of a potent cytotoxic payload but suffer from instability in human and mouse plasma with a short half-life. In addition, It also suffer from a solubility issue that induces aggregation, which is the major problem in their development. ADCs associated with sulfatase and phosphatase cleavable linker are highly soluble due to the anionic nature of sulfate and phosphate groups. The ADCs also showed high stability in human and mouse plasma. Therefore, to overcome these limitations, sulfatase and phosphatase cleavable linkers were developed. This review focuses on the recently reported advantages of sulfatase and phosphatase cleavable linkers for ADCs.

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        Synthesis of a PEGylated tracer for radioiodination and evaluation of potential in tumor targeting

        Abhinav Bhise,Sushil K. Dwivedi,이기웅,임정은,수브라므니 라즈쿠말,이웅희,조성환,유정수 대한방사성의약품학회 2021 Journal of radiopharmaceuticals and molecular prob Vol.7 No.2

        Radiopharmaceuticals are important for tumor diagnosis and therapy. To deliver a radio-tracer at the desired target excluding non-targeted tissues is difficult. The development of a targeted tracer that has a good clearance profile while maintaining high biostability and biocompatibility is key to optimizing its biodistribution and transport across biological barriers. Improving the hydrophilicity of radiotracers by PEGylation can reduce serum binding, allowing the tracer to circulate without retention and reducing its affinity for non-targeted tissues. In this study, we synthesized a new benzamido tracer (SnBz-PEG36) with the introduction of a low molecular weight polyethylene glycol unit (PEG36, ~2100 Da). The tumor-targeting efficiency and biodistribution of [131I]-Bz-PEG36 or radiotracer-loaded liposomes were evaluated after their administration to normal mice or mouse tumor models including CT26 (xenograft) and 4T1 (xenograft and orthotopic). Most of the radiotracer was cleared out rapidly (1-24 h post-administration) through the kidney and there was little tumor uptake.

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