Molecules (Basel, Switzerland) · 2026
A pH/Enzyme-Sensitive Doxorubicin Prodrug Micelle for Safe and Effective Cancer Treatment.
СтатьяНазвание и аннотация: Перевод в очереди
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Li Xiang, Wang Dan, Wu Shengyue, Na Na, Yang Xue, Yi Dongcheng, Zhang Zixi, Liang Qian, Zhao Ziming, Hua Yabing
Аннотация
OBJECTIVES: This study developed pH/enzyme-sensitive polymeric HA-AAN-DOX (HAD) micelles to resolve the limited targeting specificity of chemotherapy drugs.
METHODS: Hyaluronic acid (HA) and the chemotherapeutic agent doxorubicin (DOX) were conjugated via a hydrazone linkage utilizing an Ala-Ala-ASP tripeptide (AAN) as the connecting moiety, which is sensitive to the legumain enzyme. DOX was delivered via HAD micelles, which were activated by both hyaluronidase and the legumain enzyme.
KEY FINDINGS: The results revealed the remarkable antitumor efficacy of these micelles both in vivo and in vitro. Compared with that of doxorubicin hydrochloride (DOX·HCl), the incidence of toxic side effects was significantly reduced with the HAD micelle treatment. As a result, micelles composed of hyaluronic acid and doxorubicin (HAD) offer a reliable and effective method for drug delivery, with the potential to optimize the therapeutic impact of chemotherapeutic agents on tumors by reducing unintended side effects.
CONCLUSIONS: Micelles composed of hyaluronic acid and doxorubicin (HAD) offer a reliable and effective method for drug delivery, with the potential to optimize the therapeutic impact of chemotherapeutic agents on tumors by reducing unintended side effects.
METHODS: Hyaluronic acid (HA) and the chemotherapeutic agent doxorubicin (DOX) were conjugated via a hydrazone linkage utilizing an Ala-Ala-ASP tripeptide (AAN) as the connecting moiety, which is sensitive to the legumain enzyme. DOX was delivered via HAD micelles, which were activated by both hyaluronidase and the legumain enzyme.
KEY FINDINGS: The results revealed the remarkable antitumor efficacy of these micelles both in vivo and in vitro. Compared with that of doxorubicin hydrochloride (DOX·HCl), the incidence of toxic side effects was significantly reduced with the HAD micelle treatment. As a result, micelles composed of hyaluronic acid and doxorubicin (HAD) offer a reliable and effective method for drug delivery, with the potential to optimize the therapeutic impact of chemotherapeutic agents on tumors by reducing unintended side effects.
CONCLUSIONS: Micelles composed of hyaluronic acid and doxorubicin (HAD) offer a reliable and effective method for drug delivery, with the potential to optimize the therapeutic impact of chemotherapeutic agents on tumors by reducing unintended side effects.