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mRBD3dopa + bortezomib is an experimental protein-drug conjugate (PDC) designed for the targeted treatment of non-small cell lung cancer (NSCLC). It utilizes a mutant version of the SARS-CoV-2 receptor-binding domain (mRBD3) as a targeting ligand, which is genetically engineered to include a 3,4-dihydroxyphenyl-L-alanine (DOPA) linker. This DOPA moiety forms a reversible catechol-boronate ester bond with bortezomib, a potent 26S proteasome inhibitor. The conjugate specifically targets the Angiotensin-converting enzyme-2 (ACE2) receptor, which is frequently overexpressed in lung cancer cells. Upon binding, the complex is internalized via receptor-mediated endocytosis, and the acidic environment of the endosome triggers the controlled release of bortezomib. This targeted delivery approach aims to enhance the therapeutic efficacy of bortezomib in NSCLC while minimizing systemic toxicity and off-target effects in normal ACE2-expressing tissues.
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