Nanoparticle biointerfacing by platelet membrane cloaking.

Abstract

Development of functional nanoparticles can be encumbered by unanticipated material properties and biological events, which can affect nanoparticle effectiveness in complex, physiologically relevant systems. 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 substrates. The resulting nanoparticles possess a right-side-out unilamellar membrane coating functionalized with immunomodulatory and adhesion antigens associated with platelets. Compared to uncoated particles, the platelet membrane-cloaked nanoparticles have reduced cellular uptake by macrophage-like cells and lack 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.

• Authors: Che-Ming J Hu, Ronnie H Fang, Kuei-Chun Wang, Brian T Luk, Soracha Thamphiwatana, Diana Dehaini, Phu Nguyen, Pavimol Angsantikul, Cindy H Wen, Ashley V Kroll, Cody Carpenter, Manikantan Ramesh, Vivian Qu, Sherrina H Patel, Jie Zhu, William Shi, Florence M Hofman, Thomas C Chen, Weiwei Gao, Kang Zhang, Shu Chien, Liangfang Zhang
• Journal: Nature (Nature) Vol. 526 Issue 7571 Pg. 118-21 (Oct 01 2015) ISSN: 1476-4687 [Electronic] England
• PMID: 26374997 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Anti-Bacterial Agents
• Polymers
• Taxoids
• Unilamellar Liposomes
• Docetaxel
• Vancomycin
• Collagen

Topics

• Animals
• Anti-Bacterial Agents (administration & dosage, pharmacokinetics)
• Blood Platelets (cytology)
• Blood Vessels (cytology, metabolism, pathology)
• Cell Membrane (metabolism)
• Collagen (chemistry, immunology)
• Complement Activation (immunology)
• Coronary Restenosis (blood, drug therapy, metabolism)
• Disease Models, Animal
• Docetaxel
• Drug Delivery Systems (methods)
• Humans
• Macrophages (immunology)
• Male
• Mice
• Nanoparticles (administration & dosage, chemistry)
• Platelet Adhesiveness
• Polymers (chemistry)
• Rats
• Rats, Sprague-Dawley
• Staphylococcal Infections (blood, drug therapy, metabolism, microbiology)
• Staphylococcus aureus (cytology, metabolism)
• Taxoids (administration & dosage, pharmacokinetics)
• Unilamellar Liposomes (chemistry)
• Vancomycin (administration & dosage, pharmacokinetics)