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Cryo-Shocked Cancer Cell Biomimetic Carriers Enhance Tumor-Targeted Doxorubicin Delivery in Triple-Negative Breast
Hengcai Wang1,2, Ling Xu1, Yi Lin1
1School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang Province 325035, China.
Abstract:
Triple-negative breast cancer (TNBC) is an aggressive subtype with no defined therapeutic targets and high intratumoral heterogeneity. These features severely limit the efficacy of conventional chemotherapy. In this study, a biomimetic drug delivery platform was developed by cryo-shock treatment of 4T1 tumor cells (CS cells) to generate nonviable, structurally intact carriers, which were subsequently loaded with doxorubicin (DOX/CS cells). DOX/CS cells preserve native membrane proteins and chemotactic properties, facilitating enhanced tumor homing and tissue penetration without the risks associated with live-cell vectors. In vitro and in vivo analyses demonstrated that DOX/CS cells exhibit improved tumor-specific uptake, sustained drug release, and markedly enhanced antitumor activity compared to free DOX. Furthermore, systemic administration of DOX/CS cells achieved favorable biodistribution with minimal off-target toxicity. These findings indicate that cryo-shocked cancer cells offer a simplified yet potent platform for targeted drug delivery, offering a promising strategy for the safe and effective treatment of TNBC.
Insights
Researchers developed a novel drug delivery system using cryo-shocked cancer cells to treat triple-negative breast cancer (TNBC). This biomimetic platform enhances doxorubicin delivery to tumors, improving efficacy and reducing toxicity for a promising TNBC therapy.
Area of Science:
- Biomedical Engineering
- Oncology
- Drug Delivery Systems
Background:
- Triple-negative breast cancer (TNBC) presents significant therapeutic challenges due to its aggressive nature and high heterogeneity.
- Conventional chemotherapy efficacy is limited in TNBC, necessitating innovative treatment strategies.
Purpose of the Study:
- To develop a novel biomimetic drug delivery platform for targeted therapy of TNBC.
- To evaluate the efficacy and safety of doxorubicin-loaded cryo-shocked tumor cells (DOX/CS cells) as a treatment for TNBC.
Main Methods:
- Generation of nonviable, structurally intact cancer cell carriers (CS cells) via cryo-shock treatment of 4T1 tumor cells.
- Loading of doxorubicin (DOX) onto CS cells to create DOX/CS cells.
- In vitro and in vivo evaluation of DOX/CS cells for tumor homing, drug release, antitumor activity, and biodistribution.
Main Results:
- DOX/CS cells demonstrated enhanced tumor-specific uptake and tissue penetration compared to free DOX.
- Sustained drug release and markedly improved antitumor efficacy were observed with DOX/CS cells.
- Systemic administration of DOX/CS cells showed favorable biodistribution with minimal off-target toxicity.
Conclusions:
- Cryo-shocked cancer cells serve as a simplified and effective platform for targeted doxorubicin delivery in TNBC.
- This biomimetic approach offers a promising strategy for safe and effective treatment of triple-negative breast cancer.
- The platform leverages native cell properties for enhanced drug delivery, overcoming limitations of conventional chemotherapy.
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