Cell membrane-coated nanoparticles, applied in targeted drug delivery strategies, combine the intrinsic advantages of synthetic nanoparticles and cell membranes. Although stem cell-based delivery systems were highlighted for their targeting capability in tumor therapy, inappropriate stem cells may promote tumor growth.

A review published in the journal Materials Today Bio summarized the role of stem cell membrane-camouflaged targeted delivery system in tumor therapy and focused on the underlying mechanisms of stem cell homing toward target tumors. Nanoparticle-coated stem cell membranes have enhanced targetability, biocompatibility, and drug loading capacity.

Furthermore, the clinical applications of induced pluripotent stem cells (iPSCs) and mesenchymal stem cells (MSCs) were investigated as membrane-camouflaged targeted delivery systems for their anti-tumor therapies. In concurrence, the stem cell membrane-coated nanoparticles have immense prospects in tumor therapy.

Cell Membrane-Coated Nanoparticles Towards Tumor Therapy

Cell-based targeted delivery systems have low immunogenicity and toxicity, innate targeting capability, ability to integrate receptors, and long circulation time. Cells such as red blood cells, platelets, stem cells, tumor cells, immune cells, and even viral/bacterial cells can serve as effective natural vesicles.

MSCs derived from the umbilical cord (UC-MSCs), bone marrow (BM-MSCs), and adipose tissue (ATMSCs) are utilized in clinical applications. However, iPSCs are preferable over MSCs in clinical applications due to their easy fetch by transcription factor-based reprogramming of differentiation of somatic cells.

Stem cells (MSCs/ iPSCs) can be easily isolated and used as drug delivery systems for tumor therapy. Stem cell-based delivery systems have inflammation or tumor lesions targeting capacity. However, stem cells are often entrapped in the lung due to their size, resulting in microembolism.

Cell membrane-coated nanoparticles are applied in targeted delivery strategies. To this end, stem cell membrane-coated nanoparticles have tremendous prospects in biomedical applications. Although previous reports mentioned the role of cell membrane-coated nanocarriers in tumor therapy, delivery systems based on stem cell membranes have not been explored extensively.

Stem Cell Membrane-Coated Nanoparticles for Anti-Tumor Therapy

Stem cell membrane-coated nanoparticles obtained from stem cells have complex functioning and can achieve biological interfacing. Consequently, stem cell membrane-coated nanoparticles served as novel drug delivery systems that could effectively target the tumor.

Previous reports mentioned the preparation of doxorubicin (DOX) loaded, poly (lactic-co-glycolic acid) (PLGA) coated MSC membrane-based nanovesicles, which showed higher cellular uptake than their PLGA uncoated counterparts. Similarly, the DOX-loaded MSC membrane-coated gelatin nanogels showed enhanced storage stability and sustained drug release.

Thus, the stem cell membrane-coated nanoparticles served as novel carriers for stem cells and facilitated the targeted delivery of the drugs at the tumor site. Since the stem cell membrane-coated nanoparticles had good targeting and penetration abilities, they enhanced the efficiency of chemotherapeutic agents in tumor therapy and minimized the side effects.

Reactive oxygen species (ROS) based photodynamic therapy (PDT) is mediated by photosensitizers with laser irradiations. Previous reports mentioned the development of MSC membrane-based mesoporous silica up-conversion (SUCNPs@mSiO2) nanoparticles that efficiently targeted the tumor due to their high affinity after being coated with MSC membrane.

These cell membrane-coated nanoparticles showed high cytocompatibility (with hepatocyte cells) and hemocompatibility (with blood). Moreover, the SUCNPs@mSiOnanoparticles-based PDT therapy under 980-nanometer laser irradiations could inhibit the tumors in vivo and in vitro. Consequently, the stem cell membrane-coated nanoparticles had circulation for an extended time and escaped the immune system, thereby increasing their accumulation at the tumor site.

Stem cell membrane-coated nanoparticles were also applied to deliver small interfering RNA (siRNA) via magnetic hyperthermia therapy and imaging. Previous reports mentioned the preparation of superparamagnetic iron oxide (SPIO) nanoparticles using an MSC membrane that reduced the immune response.

Additionally, the CD44 adhesion receptors were preserved on the surface of the MSC membrane during preparation. These prepared nanovesicles were unrecognized by macrophages, which enabled their stability in blood circulation. The nanosize and tumor homing capacity of MSCs helped the nanovesicles generate a dark contrast in T2-weight magnetic resonance imaging (MRI).

Conclusion

Cell membrane-coated nanoparticles helped fabricate various targeted delivery strategies. Especially, stem cell membrane-coated nanoparticles have the following advantages: stem cells are easy to isolate and expand in vitro. Thus, multilineage potential and phenotypes could be preserved for more than 50 population doublings in vitro.

Stem cell membrane-coated nanoparticles also have an intrinsic capacity to target inflammation or tumor lesions. Hence, these nanoparticles were established for tumor therapy, building a strong foundation for stem cell membrane-mediated delivery systems.

On the other hand, stem cell membrane-coated nanoparticles have the following drawbacks: Despite various sources for collecting MSCs (UC-MSCs/BM-MSCs/ATMSCs), the number of cells obtained is limited, although iPSCs are relatively easy to fetch by reprogramming differentiated somatic cells, the reprogramming is a high-cost step, restricting the clinical applications of iPSCs.

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