In an article recently published in the journal ACS Applied Bio Materials, researchers discussed the utility of neutrophil cell membrane coating of a self-assembly nanoconstruct to enable high specificity for triple-negative breast cancer treatment.
Study: Coating a Self-Assembly Nanoconstruct with a Neutrophil Cell Membrane Enables High Specificity for Triple Negative Breast Cancer Treatment. Image Credit: crystal light/Shutterstock.com
Severity of Breast Cancer
With a 12% lifetime risk for women, breast cancer (BC) continues to be the second most prevalent cancer diagnosed in women in the United States. The majority of treatment for advanced breast cancer, metastatic breast cancer, and triple-negative breast cancer (TNBC) is the systemic injection of chemotherapeutic drugs because there are relatively few foods and drug administration (FDA)-approved medicines for such aggressive forms of the disease. The survival rate of patients was dramatically increased by chemotherapy using cytotoxic drugs. However, because of their non-specific distribution, chemotherapy might cause side effects such as induced neutropenia, cardiotoxicity, peripheral neurotoxicity, and myelosuppression.
Nanotechnology in Medical Treatment
The development of medication delivery systems based on nanotechnology has made considerable advancements in overcoming traditional constraints. Drug delivery methods based on nanoparticles (NP) have significantly advanced the field of cancer treatment.
The reticular endothelial system (RES), which clears these exogenous materials despite their therapeutic benefits, prevents tumor penetration by generating subtherapeutic concentrations in combination with a dense extracellular matrix. The use of artificial cell membranes or cell membranes obtained from nature can be included in synthetic constructs or NPs using the biomimetic NP method, a novel type of nanoplatform.
Numerous Cell Membrane-Coated Nanoparticles
Numerous cell membrane-coated NPs using membranes from platelets and nucleated cells are described in the literature. According to literature findings, NPs with cell membrane (MEM) coatings already actively express their self-markers, enabling them to adhere to tumor cells and locations.
Biomimetic Nanoparticles for the Treatment of Triple Negative Breast Cancer
In this article, the authors discussed developing a biomimetic NP construct with NPs encased in cell membranes that demonstrated a particular affinity for triple-negative breast cancer cells. The team created biomimetic supramolecular nanoconstructs with a core made of poly(vinyl pyrrolidone)-tannic acid (PVP-TA NPs/PVT NPs) and biofunctionalized with neutrophil cell membranes (PVT-NEU NPs). A PVT-NEU NP construct was synthesized, described, and tested in vitro and in vivo for enhanced targeting and therapeutic effects.
The team discussed the possibility of biomimetic NPs as a promising therapeutic choice for targeted medication delivery for advanced-stage breast cancer and other diseases of a similar nature. The creation of a perfect neutrophil-cloaked NP supramolecular construct for improved tumor-targeted administration was described. To find a suitable membrane-cloaked NP construct, various cellular binding interactions, biological tests, and bio-distribution/tumor targeting investigations were demonstrated. An ectopic xenograft tumor, the MDA-MB-231 breast cancer mouse model, was used to confirm the superior anti-tumor efficacy of the neutrophil membrane-cloaked NP construct.
The researchers demonstrated that the inherent membrane features of the proposed NPs, which resulted in improved circulation, self-binding capacity, and recognition/targeting capabilities of the source cells, allowed for successful targeting and tumor delivery overall. Due to cell-specific binding, these nanostructures not only enhanced binding to the initial tumor site but also could target the metastatic tumor.
Biological Characteristics of PVP-TA NPs
The core of PVP-TA NPs coated with activated human neutrophil membranes was present, according to the analysis of PVT-NEU NPs. The study's findings supported PVTNEU NPs' increased targeting and engagement with tumor cells, which enhanced a model therapeutic agent's therapeutic activity. In contrast to PVT NPs, PVT-NEU NPs showed pronounced binding to MDA-MB-231 and MDA-MB-468 cells, while breast epithelial cells, MCF10A, displayed very little internalization, indicating a preference for absorption in cancer cells as opposed to noncancer cells. PTX-loaded PVT NP treatment dramatically reduced the IC50 values compared to unloaded PTX.
Compared to PTX alone in MDA-MB-231, PTX-loaded PVT-NEU NPs demonstrated a substantial change of 2.95-fold reduction. When compared to PVT NPs, PVT-NEU NPs showed significantly greater tumor retention of the ICG dye after 72 hours. PTX solution demonstrated a 52% reduction in tumor growth compared to control mice.
The results of the SDS-PAGE Coomassie stain indicated that LFA-1, MAC-1, PSGL-1, and PECAM-1 could be present. Although PVT-NEU NPs appeared to have fewer proteins than NEU, the presence of membrane proteins showed that these proteins were properly translocated to the surface of PVT NPs. When the NPs were loaded with the fluorescent dye C6, there was a greater uptake of PVTNEU NPs than PVT NPs both intracellularly and in situ.
Conclusions and Future Perspectives
In conclusion, this study described the creation, improvement, and characterization of a biomimetic nanoconstruct that combined cell membrane properties and provided the NPs with a biological identity for treating breast cancer cells.
In a xenograft mouse model, neutrophil membrane-coated nanoconstructs showed tumor retention, enhanced cellular targeting, and relatively less biodistribution in healthy organs. PTX-loaded PVT-NEU NPs showed better anti-migratory, antiproliferative, and anti-colonogenic activities. Comparing this nanoconstruct to uncoated NPs and the natural drug paclitaxel, it decreased systemic toxicity, showed better in vivo therapeutic effect, and good hemocompatibility.
The authors stated that this method of biomimetic-designed nanoconstructs has promise as a drug delivery system with the potential for enhanced therapeutic outcomes, active tumor targeting, and fewer adverse effects compared to traditional chemotherapy for the treatment of breast cancer. They mentioned that the results of this study could be used to inform the design of experiments for the targeted drug delivery to the tumor site for additional disease models with comparable traits.
Chowdhury, P., Nagesh, P. K. B., Hollingsworth, TJ., Jaggi, M., Chauhan, S.C., Yallapu, M. M. (2022). Coating a Self-Assembly Nanoconstruct with a Neutrophil Cell Membrane Enables High Specificity for Triple Negative Breast Cancer Treatment. ACS Applied Bio Materials. https://pubs.acs.org/doi/10.1021/acsabm.2c00614.