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Biomimetic Nanodelivery of Biomolecules by Novel Cell Membrane-Coated Nanoparticles


The nanodelivery of biomolecules offers several benefits compared with use of the same compounds in their free form. First, payload entrapment and protection by a nanoparticle matrix minimizes the chance of interference caused by degradative agents and nonspecific cellular interactions. This helps to prolong circulation half-life and enhances the biological stability of the payload, both of which are crucial for maximizing its bioactivity. Second, owing to the relatively small size of nanocarriers, the encapsulated payloads can more tunably localize and accumulate at specific sites via common administration routes. For example, the intravenous administration of nanocarriers enables efficient bloodstream distribution and sustained tissue accumulation, whereas intra-articular injection of nanocarriers results in fast local accumulation at joint. Furthermore, intrinsic capability of nanocarriers can greatly enhance the nanodelivery efficacy. For instance, self-dissociation property of some materials at certain pH condition can facilitate the fast release of the biomolecule at local sites. By leveraging proper materials design, nanoparticulate platforms can be synthesized with specific targeting functionality and controllable release to greatly improve biomolecule payload bioavailability and ensure bioactivity at minimal dosages of the active ingredient.

The use of cell membrane coatings to camouflage existing synthetic nanomaterials is an effective biomimetic method for nanoparticle functionalization. The membrane-coated nanoparticles fabricated using such platform technology exhibit cell-mimicking properties that enable them to excel at in vivo applications. For example, red blood cell membrane coatings can greatly prolong circulation within the bloodstream, whereas platelet membrane coatings enable targeted delivery to bacteria, cancer, and damaged vasculature. It was also demonstrated that nanoparticles functionalized with white blood cell membrane can be used as nanoscale decoys to absorb and neutralize inflammatory cytokines, with potential applications for autoimmune disorders and sepsis treatment. Overall, cell membrane coatings can be derived from any type of cell, enabling researchers a wide range of options for adding functionality and creating synergies with nanoparticle-based biomolecule delivery.

Herein, we discuss biomimetic nanodelivery of several biomolecules by novel cell-membrane coated nanoparticles. The biomimetic delivery techniques developed from novel formulations encased of liquid perfluorocarbon for oxygen delivery, to new methods composed of metal-organic framework for small-interfering RNA and enzyme delivery. Specifically, red blood cell membrane-coated oxygen-loaded perfluorocarbon nanoemulsions can act as a promising candidate of next-generation blood substitute with tremendous physiological stability, prolonged blood circulation and excellent biocompatibility, which may have the potential to address a critical need in the clinic. On the other hand, platelet membrane-coated small-interfering RNA-loaded metal-organic framework nanoparticles present high silencing efficiency against multiple target genes, which could be used to expand the applicability of gene therapy across a range of disease-relevant applications. Moreover, macrophage membrane-coated enzyme-loaded metal-organic framework nanoparticles show excellent local retention and cytokine neutralization, thus can synergize with the loaded enzyme for degradation of cognate substrate and alleviation of relevant disease. Taking together, these biomimetic approaches by novel cell membrane-coated nanoparticles will hopefully lead to better use of the biomolecules and treatment of the diseases, and a higher level of tailoring ability available to engineers designing future platforms.

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