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A ROS-Responsive Self-Assembly Driven by Multiple Intermolecular Interaction Enhances Tumor-Targeted Chemotherapy.
Yongfu Xiong1, Gang Yang2, He Zhou3
1Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China; Institute of Hepato-Biliary-Pancreatic-Intestinal Disease, North Sichuan Medical College, Nanchong 637000, China.
Journal of Pharmaceutical Sciences
|November 17, 2020
Summary
This study presents a novel drug carrier, AD@sHA, designed to release chemotherapy drugs in response to reactive oxygen species (ROS). This targeted approach enhances cancer cell death and reduces side effects for improved chemotherapy outcomes.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Cancer Therapy
Background:
- Developing targeted drug delivery systems is crucial for enhancing cancer chemotherapy efficacy.
- Reactive oxygen species (ROS) are key indicators of tumor microenvironments, offering a target for stimuli-responsive drug release.
- Hyaluronic acid and anthocyanin offer biocompatible and functional components for drug carrier design.
Purpose of the Study:
- To create a novel nanocomplex (NCs) based on sulfuric hyaluronic acid (sHA) and anthocyanin (ATC) for ROS-sensitive drug delivery.
- To load Doxorubicin (DOX) into the sHA-ATC NCs (AD@sHA) and evaluate its characteristics.
- To investigate the therapeutic potential of AD@sHA in CD44+ colon cancer models.
Main Methods:
- Preparation of AD@sHA nanocomplexes via simple aqueous mixing.
- Characterization of DOX loading efficiency and content within AD@sHA.
- In vitro assessment of ROS-mediated degradation and drug release kinetics.
- In vitro evaluation of AD@sHA-induced apoptosis in CD44+ HT29 colon cancer cells.
- In vivo studies using HT29 tumor-bearing mice to assess tumor growth, biodistribution, and myelosuppression.
Main Results:
- High DOX loading content and efficiency achieved in AD@sHA.
- Confirmed ROS- and ATC-mediated responsive degradation and enhanced drug release from AD@sHA compared to D@sHA.
- AD@sHA demonstrated improved apoptosis induction in CD44+ HT29 cells.
- In vivo studies showed optimized DOX biodistribution, delayed tumor growth, and significant cancer cell apoptosis.
- AD@sHA significantly reduced DOX-induced myelosuppression.
Conclusions:
- The developed AD@sHA nanocomplex is a promising ROS-sensitive drug carrier for targeted cancer therapy.
- AD@sHA exhibits enhanced efficacy in treating CD44-positive colon tumors with reduced systemic toxicity.
- This study highlights the potential of sHA-ATC NCs for advanced chemotherapy applications.
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