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A New Nanoplatform With Dual-Mode Therapeutic Pathways

A novel biomimetic membrane designed by researchers at Hefei Institutes of Physical Sciences and Binzhou Medical University can not only successfully deliver drugs to cancer cells but also induce cancer cell death by generating radicals.

Separating cellular contents from the outside environment is the basic function of a cell membrane, which is a lipid bilayer that protects our cells. In recent years, the cell membrane has been gaining popularity as a promising delivery nanocarrier, displaying potential in transporting active biomolecules or therapeutic drugs to their target site. However, the complexity of preparation technology, unpredictable morphology, and poor colloid stability, seriously limits cell membrane-based drug delivery systems in the clinical setting. Therefore, there is a need to develop simpler and higher-yielding methods for preparing biomimetic cell membranes.

Recently, results published in the Journal of Nanobiotechnology revealed that a simple self-assembled biomimetic cytomembrane-based nanoplatform exhibited successful internalisation into cancer cells, generating abundant reactive oxygen species that damage mitochondria and induce cancer cell death.

In this study, researchers led by Professor Wu Zhengyan from the Institute of Intelligent Machines at Hefei Institutes of Physical Sciences (HFIPS) of the Chinese Academy of Sciences, together with collaborators from the Institute of Health and Medical Technology of HFIPS and Binzhou Medical University, prepared a biomimetic membrane derived from Pseudomonas geniculate cells. The membrane was then coated with nanoselenium and manganese ions, which caused the membrane to display a negative zeta potential. This allows the researchers to load the chemotherapy drug doxorubicin through electrostatic interactions.

Subsequently, cellular uptake of the drug-loaded nanocarrier was observed through confocal laser scanning microscopy. They found that the manganese-coated biomimetic membrane could be efficiently taken up by cancer cells as compared to traditional membrane-based drug delivery systems. As the internalisation efficiency is greater, more doxorubicin can be transported to cancer cells.

Apart from delivering drugs more efficiently, the team considered the possibility of generating reactive oxygen species that could induce cell death. As it is known that manganese ions can catalyse the production of hydroxyl radicals through Fenton-like reactions, the team investigated the generation of hydroxyls by detecting 2’,7’-dichlorodihydrofluorescein diacetate after treatment with manganese and nanoselenium-coated nanoparticles. With the controls, the team reported negligible green fluorescence. However, with their ion-coated biomimetic membrane, the team observed bright green fluorescence, which suggests that manganese and nanoselenium ions could enhance the intracellular generation of reactive oxygen species.

By utilising Fenton-like reactions to generate hydroxyl radicals, the team’s novel biomimetic membrane could solve the problem of multi-drug resistance by initiating the mitochondria-mediated cell death pathway. The success displayed in this study provides new opportunities for biomedical engineering research and nanomedicine. [APBN]

Source: Xiao et al. (2021). A nanoselenium-coating biomimetic cytomembrane nanoplatform for mitochondrial targeted chemotherapy- and chemodynamic therapy through manganese and doxorubicin codelivery. Journal of nanobiotechnology, 19(1), 1-16.