Biomimetic Anisotropic-Functionalized Platelet-Membrane-Coated Polymeric Particles for Targeted Drug Delivery to Human Breast Cancer Cells

Abstract

Biomimetic particles that can replicate aspects of natural biological cell function are useful for advanced biological engineering applications. Engineering such particles requires mimicking the chemical complexity of the surface of biological cells, and this can be achieved by coating synthetic particles with naturally derived cell membranes. Past research has demonstrated the feasibility of utilizing cell membrane coatings from a variety of cell types to achieve extended blood circulation half-life. A particle’s shape can also be designed to mimic a biological cell or virus, and this physical attribute can cause particular transport and biodistribution properties. However, the potential synergy between engineering a biomimetic particle’s core shape in combination with functionalizing its surface with cell membranes to achieve targeted drug delivery has not been well-investigated. Here, anisotropic poly(lactic-co-glycolic acid) (PLGA) particles are coated with platelet membranes to engineer particles with enhanced stealth properties that are biomimetic in size, shape, and surface composition to natural platelets. The natural ability of platelets to target tumor cells was harnessed to develop a particulate system for targeted dual delivery of a small molecule and protein to cancer cells. The particles had targeted binding to metastatic human breast cancer cells, leading to enhanced killing of these cells in a mouse model through codelivery of TRAIL and doxorubicin. This system can be used for cancer cell killing and could potentially be utilized in preventing breast cancer metastasis. By engineering both the physical and chemical properties of the particles, biomimicry and therapeutic promise can be best achieved.