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Enzymatic Nanosphere‐to‐Nanofiber Transition and Autophagy Inducer Release Promote Tumor Chemotherapy

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Chemotherapy has remained an effective and predominant cancer treatment for the past decades, but is hampered by its low response rate and severe systemic toxicity. Combination chemotherapies are proposed to… Click to show full abstract

Chemotherapy has remained an effective and predominant cancer treatment for the past decades, but is hampered by its low response rate and severe systemic toxicity. Combination chemotherapies are proposed to address these issues, yet their therapeutic outcomes are still far from satisfactory. Thus, it is urgent to develop novel strategies to promote tumor chemosensitivity while reducing toxic side effects of chemotherapeutics. Herein, employing a rationally designed peptide conjugate Nap‐Phe‐Phe‐Lys(SA‐AZD8055)‐Tyr(H2PO3)‐OH (Nap‐AZD‐Yp), a novel approach of simultaneous intracellular nanofiber formation and autophagy inducer release is proposed for selectively sensitizing tumor to chemotherapy. Upon sequential catalyses of alkaline phosphatase and carboxylesterase, Nap‐AZD‐Yp undergoes nanosphere‐to‐nanofiber transition accompanied by autophagy inducer AZD8055 release in cancer cells. Cell experiments show enhanced endocytosis of anticancer drug doxorubicin and inhibition of cell migration due to the intracellular nanofiber formation. The released AZD8055 further activates excessive autophagy of cancer cells, sensitizing them to chemotherapy. Animal experiment results suggest Nap‐AZD‐Yp can significantly enhance the therapeutic effects of doxorubicin on tumors while mitigate its toxic adverse effects on normal tissues. It is anticipated that the “smart” concept in this work c be widely employed to develop novel combinational therapies for the treatment of cancers and other diseases in near future.

Keywords: tumor; autophagy inducer; release; chemotherapy

Journal Title: Advanced Healthcare Materials
Year Published: 2022

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