Professor Wang Wei's team from the State Key Laboratory of Natural Medicine, School of Pharmacy, China Pharmaceutical University published a paper entitled “A minimally designed PD-L1-targeted nanocomposite for positive feedback-based multimodal cancer therapy” in Materials Today (IF=26.943, top journal in Q1). Professor Wang Wei’s team found that new targeted nanocomposites can positively feedback mediate multimodal cancer treatment.
In this research, our Aniview 600 in vivo imaging system was applied to detect the tumor accumulation effect.
Combining immune checkpoint blockade therapy (ICBT) with other treatment methods through nanotechnology provides an opportunity to enhance immunity and effectively treat cancer.
Recently, Professor Wang Wei’s team generated a three-in-one PD-L1 targeted nanocomposite material (NC) by self-assembly of photothermal agent black phosphorus nanosheets (BPN), chemotherapy agent poly metformin (PolyMet), and immune checkpoint inhibitor anti-PD-L1 antibody (aPD-L1), bridging the electrostatic interaction between PolyMet and BPN to avoid the easy degradation of BPN.
The prepared aPD-L1-PolyMet/BPN NC can precisely target the primary tumor through the interaction between aPD-L1 and PD-L1 based on ICBT. Due to the upregulation of PD-L1 at the tumor site after photothermal therapy (PTT), the targeting effect is gradually strengthened, ensuring the realization of positive feedback mediated multimode anti-tumor effect in the continuous treatment cycle.
In addition, the combination of photothermal immunotherapy (PIT), chemotherapy, and ICBT enhances anti-tumor efficacy due to their synergistic mechanism. At the same time, the positive feedback characteristic generated in the treatment process shows a strong anti-tumor effect, which can not only inhibit the progress of primary and distal tumors but also prevent tumor metastasis and promote the establishment of long-term immunological memory of tumors.
Figure1: Schematic illustration of the positive feedback-mediated multimodal tumor therapy based on minimally designed aPD-L1-PolyMet/BPN NC. (a) Synthesis of aPD-L1-PolyMet/BPN. (b) Positive feedback-based tumor treatment process through PD-L1-targeting of aPD-L1-PolyMet/BPN. (c) The therapeutic outcome after treatment with aPD-L1-PolyMet/BPN plus NIR irradiation.
PTB mice were randomly divided into aPD-L1 PolyMet/BPN+L, aPD-L1 PolyMet/BPN, PolyMet/BPN+L, and IgG PolyMet/BPN+L groups (n=3). In the experiment, BLT Biotechnology’s AniView series multimodal animal imaging system was used to detect the tumor accumulation effects of various NCs at 24, 48, 72, 96, 120, 144, and 168 hours. Each imaging is performed immediately before the next intravenous injection of medication or PTT (808 nm, 1.5 W/cm2, 10 minutes). After the last imaging at 168 hours, all mice were sacrificed and each tumor tissue was collected for in vitro imaging.
Firgure2: Positive feedback mediated tumor, targeting of various BPN formulations during anti-tumor therapy
The aPD-L1-PolyMet/BPN designed by the research team can not only effectively eradicate tumors through multimodal treatment, but also show good positive feedback mediated tumor killing effect after NIR irradiation, strengthening the tumor targeting and combined treatment effect based on ICBT.
The accumulation of aPDL1 PolyMet/BPN at the tumor site after treatment can enhance anti-tumor effects, effectively inhibit primary and distal tumor progression, and avoid tumor metastasis. In addition, PD-L1 targets based on positive feedback can further synergize anti-metastasis by blocking the PD-1/PD-L1 signal pathway (ICBT) through PIT and chemotherapy. In summary, this NC demonstrates the potential for multimodal cancer treatment, with enormous research value and clinical benefits.
Guangzhou Biolight Biotechnology Co., Ltd (BLT) is specializes in the development and manufacturing of high efficiency optical imaging technologies. The technology has many applications to the fields of life science research, food safety testing, environmental quality monitoring as well as medical diagnostics. Our product series includes in vivo imaging systems for animals and plants. We also offer gel and blotting imaging and an accompanying sample preparation and Luminescence Detection system.
Reference:
Yijun Mei, Lu Tang, Lidong Zhang, Jingyi Hu, Ziyao Zhang, Shun He, Jing Zang, Wei Wang, A minimally designed PD-L1-targeted nanocomposite for positive feedback-based multimodal cancer therapy, Materials Today,Volume 60,2022, Pages 52-68, ISSN 1369-7021, https://doi.org/10.1016/j.mattod.2022.09