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Tumor microenvironment targeting system for glioma treatment via fusion cell membrane coating nanotechnology
Junning Ma1, Lisi Dai2, Jianbo Yu3
1Department of Neurosurgery of First Affiliated Hospital, Zhejiang University School of Medicine, China; School of Medicine Zhejiang University, China.
Abstract:
The tumor microenvironment (TME), comprising cancer cells and stroma, plays a significant role in determining clinical outcomes, which makes targeting cancer cells in the TME an important area of research. One way in which cancer cells in the TME can be specifically targeted is by coating drug-encapsulated nanoparticles (NPs) with homotypic cancer cell membranes. However, incomplete targeting is inevitable for biomimetic nanoformulations coated with only cancer cell membranes because of the inherent heterogeneity of the TME. After observing the structural connection between glioma-associated stromal cells (GASCs) and glioma cells from a clinic, we designed a novel drug delivery system that targets the TME by coating polylactic-co-glycolic acid (PLGA) NPs with GASC-glioma cell fusion cell (SG cell) membranes. The resulting SGNPs inherited membrane proteins from both the glioma membrane and GASC membrane, significantly enhancing the tumor targeting efficiency compared to nanoformulations coated with cancer cell membranes alone. We further demonstrated that encapsulation of temozolomide (TMZ) improved the therapeutic efficacy of TMZ in both heterotopic and orthotopic glioma mouse models. Owing to its significant efficacy, our TME-targeting nanoplatform has potential for clinical applications in the treatment of various cancers.
Insights
This study introduces a novel nanoplatform for targeting the tumor microenvironment (TME). By fusing cancer and stromal cell membranes, these nanoparticles enhance drug delivery and therapeutic efficacy in glioma models.
Area of Science:
- Oncology
- Materials Science
- Nanotechnology
Background:
- The tumor microenvironment (TME) significantly influences cancer progression and treatment outcomes.
- Targeting cancer cells within the TME is crucial for effective cancer therapy.
- Current biomimetic nanoformulations face limitations due to TME heterogeneity.
Purpose of the Study:
- To develop an advanced drug delivery system for enhanced tumor targeting.
- To overcome the limitations of conventional cancer cell membrane-coated nanoparticles.
- To improve the therapeutic efficacy of chemotherapy in glioma models.
Main Methods:
- Designed polylactic-co-glycolic acid (PLGA) nanoparticles coated with fused glioma-stromal cell membranes (SG cell membranes).
- Investigated the targeting efficiency of the novel SG-nanoparticles (SGNPs) compared to cancer cell membrane-coated nanoparticles.
- Encapsulated temozolomide (TMZ) within SGNPs and evaluated its therapeutic efficacy in preclinical glioma models.
Main Results:
- SGNPs exhibited significantly enhanced tumor targeting efficiency compared to nanoparticles coated solely with cancer cell membranes.
- The fused membrane coating successfully integrated proteins from both cell types, improving biomimicry.
- TMZ-loaded SGNPs demonstrated improved therapeutic efficacy in both heterotopic and orthotopic glioma mouse models.
Conclusions:
- The novel SGNP platform offers superior TME targeting capabilities.
- This nanoplatform holds significant potential for clinical applications in treating various cancers.
- The strategy of fusing cancer and stromal cell membranes presents a promising approach for next-generation cancer nanotherapeutics.
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