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Life sciences · Journal article
Journal of Nanobiotechnology · October 31, 2026
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Bladder cancer (BC) remains a significant health concern, necessitating the development of innovative therapeutic approaches. Herein, a novel strategy is developed utilizing BC cell surface receptor-mediated, transformable peptide nanoparticles, where the prodrug leucine-doxorubicin (Leu-DOX) and the PLZ4 ligand are linked by a β-sheet-forming peptide sequence, KLVFF, to enhance drug delivery efficacy while minimizing toxicity. These transformable peptides self-assemble into nanoparticles with high specificity for BC tissues through the specific recognition of αvβ3 integrin via PLZ4. Upon binding to αvβ3 integrin, the nanoparticles undergo a transformation process facilitated by ligand-receptor interaction, forming nanofibrils on the cancer cell surface, followed by gradual uptake by the cancer cells. In response to matrix metallopeptidase 9 (MMP-9) overexpressed in the tumor microenvironment, the conjugate is cleaved to release the Leu-DOX prodrug, which is subsequently converted into active doxorubicin inside the tumor cells, leading to effective tumor cell elimination. These findings suggest substantial implications for the development of targeted therapies for BC.