# A pH/Enzyme-Sensitive Doxorubicin Prodrug Micelle for Safe and Effective Cancer Treatment

## TL;DR

This paper introduces a new micelle-based drug delivery system that improves cancer treatment by targeting tumors more precisely and reducing side effects.

## Contribution

The novel contribution is the development of pH/enzyme-sensitive HAD micelles for targeted doxorubicin delivery.

## Key findings

- HAD micelles showed remarkable antitumor efficacy in both in vivo and in vitro studies.
- Compared to doxorubicin hydrochloride, HAD micelles significantly reduced toxic side effects.

## Abstract

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.