Selective Tumor Treatment Targeting CAIX with Low Toxicity Range by Interrupting Lysosome
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- Selective Tumor Treatment Targeting CAIX with Low Toxicity Range by Interrupting Lysosome
- Kim, Dohyun; Ryu, Ja-Hyoung
- Issue Date
- Korean Chemical Society
- 125th General Meeting of the Korean Chemical Society
- Lysosome, which degrades and recycles cellular waste, is a vital organelle to maintain cellular signaling and metabolism. Therefore, lysosome has been emerged as an efficient therapeutic target to treat cancer cell. To induce lysosomal disruption, researcher has been used self-assembly structure that interacts with organelle membrane. Carbonic anhydrase IX (CAIX), which is overexpressed cancer cell, has a key role to signal transduction of tumor including cell proliferation, metastasis, angiogenesis. CAIX targeting strategy has been developed to give selective cellular uptake by using Acetazolamide as a CAIX targeting moiety. Here, we developed Pep-AT containing acetazolamide, which is carbonic anhydrase IX targeting moiety, and triphenylphosphonium (TPP), which is organelle interacting moiety. As Pep-AT selectively binds CAIX of cancer cell, self-assembly structure of Pep-AT can be generated. Self-assembly structure can be encapsulated inside lysosome by CAIX-mediated endocytosis. Interaction between lysosomal membrane and self-assembly structure can induce lysosomal disruption, as followed by cellular apoptosis.
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