Related Experiment Video
Updated: Mar 24, 2026
Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
A Targeted Nanozyme for STING Activation Improves BiTEs Therapy Outcomes in Colorectal Cancer
1Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, Department of Radiation Oncology and Department of Head and Neck Oncology, West China Hospital, Sichuan University, Chengdu, China.
Abstract:
Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, with limited efficacy of conventional therapies due to immunosuppressive tumor microenvironments and high recurrence. While bispecific T-cell engagers (BiTEs) show promise by engaging T cells against tumors, their clinical translation is hindered by poor stability, on-target off-tumor effect, and systemic toxicity. Herein, we develop a tumor-targeted nanozyme (MnO2-dsDNA@BiTE/APT) that co-delivers hydrolytically stable double-strand DNA (dsDNA: a STING agonist) and PD-L1/CD3 BiTE to overcome these limitations. The nanozyme leverages MnO2 as a carrier for dsDNA, surface-loaded with BiTE via polyphenol-protein coordination, and functionalized with an aptamer (APT) for active targeting. Upon systemic administration, the nanozyme accumulates in tumors, releasing dsDNA, Mn2+, and BiTE. The synergistically activates the STING pathway to remodel the immunosuppressive microenvironment and enhances T cell-mediated cytotoxicity. This strategy represents a promising approach for potentiating immunotherapy in CRC by integrating innate immune activation with adaptive T cell engagement.
Insights
This study introduces a novel nanozyme therapy for colorectal cancer (CRC) that combines innate immune activation with targeted T-cell engagement, improving treatment efficacy against immunosuppressive tumors.
Area of Science:
- Oncology
- Immunotherapy
- Nanomedicine
Background:
- Colorectal cancer (CRC) presents a significant global health challenge due to treatment resistance and high recurrence rates, often linked to immunosuppressive tumor microenvironments.
- Conventional therapies and existing bispecific T-cell engagers (BiTEs) face limitations including poor stability, off-tumor effects, and systemic toxicity, hindering effective cancer immunotherapy.
Purpose of the Study:
- To develop a novel tumor-targeted nanozyme capable of co-delivering immunomodulatory agents and T-cell engaging bispecific antibodies for enhanced colorectal cancer treatment.
- To overcome the limitations of current immunotherapies by creating a stable, tumor-specific delivery system that activates innate immunity and adaptive T-cell responses.
Main Methods:
- A nanozyme (MnO2-dsDNA@BiTE/APT) was engineered, utilizing manganese dioxide (MnO2) to carry double-strand DNA (dsDNA), a STING agonist, and surface-loading with a PD-L1/CD3 bispecific T-cell engager (BiTE).
- The nanozyme was functionalized with an aptamer (APT) for active tumor targeting, enabling localized release of dsDNA, Mn2+, and BiTE upon reaching the tumor site.
- The study investigated the synergistic effects of dsDNA-mediated STING pathway activation and BiTE-induced T-cell cytotoxicity in remodeling the tumor microenvironment.
Main Results:
- The developed nanozyme demonstrated effective tumor accumulation and localized release of its therapeutic payloads (dsDNA, Mn2+, BiTE).
- Co-delivery synergistically activated the STING pathway, successfully remodeling the immunosuppressive tumor microenvironment.
- Enhanced T-cell-mediated cytotoxicity was observed, indicating potentiation of the anti-tumor immune response.
Conclusions:
- The tumor-targeted nanozyme represents a promising strategy for enhancing colorectal cancer immunotherapy by integrating innate immune stimulation with adaptive T-cell engagement.
- This approach offers a potential solution to overcome the challenges of immunosuppression and recurrence in colorectal cancer treatment.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:28Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
01:15Drugs that Stabilize Microtubules