Nanoparticle biointerfacing by platelet membrane cloaking

Abstract

Development of functional nanoparticles can be encumbered by unanticipated material properties and biological events, which can negatively impact nanoparticle effectiveness in complex, physiologically relevant systems1–3. Despite the advances in bottom-up nanoengineering and surface chemistry, reductionist functionalization approaches remain inadequate in replicating the complex interfaces present in nature and cannot avoid exposure of foreign materials. Here we report on the preparation of polymeric nanoparticles enclosed in the plasma membrane of human platelets, which are a unique population of cellular fragments that adhere to a variety of disease-relevant substrates4–7. The resulting nanoparticles possess a right-side-out unilamellar membrane coating functionalized with immunomodulatory and adhesion antigens associated with platelets. As compared to uncoated particles, the platelet membrane-cloaked nanoparticles have reduced cellular uptake by macrophage-like cells and are absent of particle-induced complement activation in autologous human plasma. The cloaked nanoparticles also display platelet-mimicking properties such as selective adhesion to damaged human and rodent vasculatures as well as enhanced binding to platelet-adhering pathogens. In an experimental rat model of coronary restenosis and a mouse model of systemic bacterial infection, docetaxel and vancomycin, respectively, show enhanced therapeutic efficacy when delivered by the platelet-mimetic nanoparticles. The multifaceted biointerfacing enabled by the platelet membrane cloaking method provides a new approach in developing functional nanoparticles for disease-targeted delivery.

The Impact of Nanoparticle Protein Corona on Cytotoxicity, Immunotoxicity and Target Drug Delivery

“…Hu et al demonstrated that red blood cell molecules were correctly transferred and oriented on the NPs surfaces [159]. Other bio-inspired NPs whose surface is functionalized through the integration of cell membranes, have been developed [153,[156][157]160]. Among these, we used membrane proteins purified from leukocytes [161] to obtain the Leuko-like Vector (i.e., a nanopourous silica NP coated with leukocyte membranes).…”

“…To date, no studies have been performed in order to describe the PC of bio-inspired NPs. (B) We hypothesize that while a synthetic NP is mainly recognized as nonself and adsorbs many serum proteins; bio-inspired NPs (reported to possess celllike capabilities [155][156][157]) absorb a specific PC similar to the PC of the cells used as membrane source for the NP synthesis. This confers self-like properties to the bio-inspired NPs and mediates their biological activity.…”

“…The transfer of cellular membrane properties to synthetic NPs led to the development of the so-called biomimetic strategies. Specialized cell types (A), such as red blood cells [155], leukocytes [156] or platelets [157], inspired the development of particles that share a similar cellular membrane composition. The resulting vectors, defined as 'bio-inspired NPs', are recognized as self by the immune system.…”

Therapeutic biomaterials based on extracellular vesicles: classification of bio‐engineering and mimetic preparation routes

“…These authors have produced unilamellar polymeric nanoparticles functionalized with immunomodulatory and adhesion antigens, and they have tested them as another approach to disease-targeted delivery [115]. …”

Gambogic acid-loaded biomimetic nanoparticles in colorectal cancer treatment

“…Furthermore, immunoevasion led by membrane coating made the RBCm-GA/PLGA group slightly better than the GA/PLGA group. In future work, achieving a specific active target by utilizing specific membranes derived from selected cells, 36 such as cancer cells, [37][38][39][40] or via targeting ligands inserted into membranes 41,42 can be designed to build a nanocarrier with better antitumor effect.…”