Related Experiment Video
Updated: Jul 26, 2025
Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
Biomimetic black phosphorus nanosheets codeliver CDK9 and BRD4 inhibitors for gastric cancer targeted therapy
Zhe Zhang1, Xiaoyi Zhang1, Zhaojun Ren1
1Department of Pathology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, P. R. China. loukexin@njmu.edu.cn.
Abstract:
Combining the BRD4 and CDK9 inhibitors can trigger the significant down-regulation of the MYC oncogene as well as anti-apoptotic genes and induce tumor cell apoptosis by synergistically impairing RNA synthesis in cancer cells. However, the lack of tumor-targeting capacity and the different pharmacokinetic curves of these two inhibitors may impair the antitumor activity of simultaneous CDK9 and BRD4 inhibition. Herein, CDK9 inhibitor (CI) and BRD4 inhibitor (BI) were codelivered by macrophage membrane-encapsulated black phosphorus nanosheets (M@BP) for the treatment of gastric cancer (GC) via the high expression of BRD4 and CDK9. BP with prominent biocompatibility exhibited a high drug loading efficiency for both CI and BI and could efficiently decrease the expression of the MYC oncogene. More importantly, BP could also serve as a phototherapy agent collaborating with CDK9 and BRD4 inhibition for GC therapy upon near-infrared (NIR) irradiation. Furthermore, the introduction of a macrophage membrane endowed BP with tumor-targeting ability, which could simultaneously deliver CI and BI to tumor tissues. In a murine orthotopic GC model, M@BP could efficiently target and accumulate in the tumor tissues, exhibiting an excellent photothermal effect. The tumor growth monitoring demonstrated that the combination of CI and BI codelivered by M@BP significantly inhibited the tumor progress than the single inhibitors, and the inhibition effect could be further enhanced upon NIR irradiation. Taken together, M@BP with tumor-targeting capacity and high drug loading efficiency for CI and BI could efficiently block the activation of CDK9 and BRD4, exhibiting excellent antitumor activity under NIR irradiation without systemic toxicity in an orthotopic GC model.
Insights
Macrophage-encapsulated black phosphorus nanosheets (M@BP) co-deliver BRD4 and CDK9 inhibitors for gastric cancer. This targeted therapy enhances antitumor activity, especially with near-infrared irradiation, showing reduced tumor growth and toxicity.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Simultaneous inhibition of BRD4 and CDK9 downregulates MYC and anti-apoptotic genes, inducing cancer cell apoptosis.
- Tumor-targeting delivery and compatible pharmacokinetics are crucial for effective co-delivery of BRD4 and CDK9 inhibitors.
- Gastric cancer (GC) exhibits high expression of BRD4 and CDK9, making it a potential target for combined inhibition therapy.
Purpose of the Study:
- To develop a targeted co-delivery system for BRD4 inhibitor (BI) and CDK9 inhibitor (CI) for gastric cancer (GC) treatment.
- To investigate the synergistic antitumor effects of co-delivered BI and CI, enhanced by phototherapy.
- To evaluate the efficacy and safety of macrophage membrane-encapsulated black phosphorus nanosheets (M@BP) in an orthotopic GC model.
Main Methods:
- Macrophage membranes were used to encapsulate black phosphorus nanosheets (BP) loaded with CI and BI (M@BP).
- BP nanosheets were characterized for drug loading efficiency and biocompatibility.
- The antitumor efficacy of M@BP was evaluated in a murine orthotopic GC model, with and without near-infrared (NIR) irradiation.
Main Results:
- M@BP demonstrated high drug loading efficiency for both CI and BI and effectively reduced MYC oncogene expression.
- M@BP exhibited tumor-targeting ability, accumulating in tumor tissues and showing a photothermal effect upon NIR irradiation.
- Co-delivery of CI and BI by M@BP significantly inhibited tumor progression compared to single inhibitors, with enhanced efficacy under NIR irradiation and minimal systemic toxicity.
Conclusions:
- M@BP serves as an effective platform for co-delivering CI and BI, leveraging the targeting ability of macrophage membranes and the photothermal properties of BP.
- This targeted nanomedicine approach demonstrates potent antitumor activity against gastric cancer, particularly when combined with NIR phototherapy.
- The M@BP system offers a promising strategy for enhancing the therapeutic outcomes of combined BRD4 and CDK9 inhibition in gastric cancer treatment with improved safety profiles.
More Related Videos
10:28Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT
Published on: January 22, 2018
09:02Author Spotlight: Innovative Cancer Therapies with Iron Oxide Nanoparticles for Glioblastoma Treatment
Published on: September 27, 2024
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:34Inhibition of Cdk Activity
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...