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CatB-NPs are cathepsin B-activatable doxorubicin prodrug nanoparticles designed for the targeted treatment of melanoma. The drug consists of doxorubicin conjugated to a cathepsin B-cleavable peptide linker (Phe-Arg-Arg-Leu, or FRRL). These amphiphilic prodrugs self-assemble into stable nanoparticles that remain inactive in systemic circulation, minimizing off-target toxicity. Upon reaching the tumor microenvironment, which often overexpresses the lysosomal protease cathepsin B, the peptide linker is cleaved, releasing active doxorubicin. This localized release induces tumor-specific immunogenic cell death (ICD), promoting dendritic cell maturation and T-cell activation. In preclinical studies, CatB-NPs have shown synergy with immune checkpoint inhibitors like anti-PD-L1 antibodies, leading to enhanced anti-tumor immunity and reduced metastatic burden.
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