Brian T. Luk

Cell-derived nanoparticles have been garnering increased attention due to their ability to mimic many of the natural properties displayed by their source cells. This top-down engineering approach can be applied toward the development of novel therapeutic strategies owing to the unique interactions enabled through the retention of complex antigenic information. Herein, we report on the biological functionalization of polymeric nanoparticles with a layer of membrane coating derived from cancer cells. The resulting core-shell nanostructures, which carry the full array of cancer cell membrane antigens, offer a robust platform with applicability toward multiple modes of anticancer therapy. We demonstrate that by coupling the particles with an immunological adjuvant, the resulting formulation can be used to promote a tumor-specific immune response for use in vaccine applications. Moreover, we show that by taking advantage of the inherent homotypic binding phenomenon frequently observed among tumor cells the membrane functionalization allows for a unique cancer targeting strategy that can be utilized for drug delivery applications.

Cell-membrane-coated nanoparticles have recently been studied extensively for their biological compatibility, retention of cellular properties, and adaptability to a variety of therapeutic and imaging applications. This class of nanoparticles, which has been fabricated with a variety of cell membrane coatings, including those derived from red blood cells (RBCs), platelets, white blood cells, cancer cells, and bacteria, exhibit properties that are characteristic of the source cell. In this study, a new type of biological coating is created by fusing membrane material from two different cells, providing a facile method for further enhancing nanoparticle functionality. As a proof of concept, the development of dual-membrane-coated nanoparticles from the fused RBC membrane and platelet membrane is demonstrated. The resulting particles, termed RBC-platelet hybrid membrane-coated nanoparticles ([RBC-P]NPs), are thoroughly characterized, and it is shown that they carry properties of both source cells. Further, the [RBC-P]NP platform exhibits long circulation and suitability for further in vivo exploration. The reported strategy opens the door for the creation of biocompatible, custom-tailored biomimetic nanoparticles with varying hybrid functionalities, which may be used to overcome the limitations of current nanoparticle-based therapeutic and imaging platforms.