Diana Dehaini

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.

Anticancer vaccines train the body's own immune system to recognize and eliminate malignant cells based on differential antigen expression. While conceptually attractive, clinical efficacy is lacking given several key challenges stemming from the similarities between cancerous and healthy tissue. Ideally, an effective vaccine formulation would deliver multiple tumor antigens in a fashion that potently stimulates endogenous immune responses against those antigens. Here, it is reported on the fabrication of a biomimetic, nanoparticulate anticancer vaccine that is capable of delivering autologously derived tumor antigen material together with a highly immunostimulatory adjuvant. The two major components, tumor antigens and adjuvant, are presented concurrently in a fashion that maximizes their ability to promote effective antigen presentation and activation of downstream immune processes. Ultimately, it is demonstrated that the formulation can elicit potent antitumor immune responses in vivo. When combined with additional immunotherapies such as checkpoint blockades, the nanovaccine demonstrates substantial therapeutic effect. Overall, the work represents the rational application of nanotechnology for immunoengineering and can provide a blueprint for the future development of personalized, autologous anticancer vaccines with broad applicability.

The unique structural features and stealth properties of a recently developed red blood cell membrane-cloaked nanoparticle (RBC-NP) platform raise curiosity over the interfacial interactions between natural cellular membranes and polymeric nanoparticle substrates. Herein, several interfacial aspects of the RBC-NPs are examined, including completeness of membrane coverage, membrane sidedness upon coating, and the effects of polymeric particles' surface charge and surface curvature on the membrane cloaking process. The study shows that RBC membranes completely cover negatively charged polymeric nanoparticles in a right-side-out manner and enhance the particles' colloidal stability. The membrane cloaking process is applicable to particle substrates with a diameter ranging from 65 to 340 nm. Additionally, the study reveals that both surface glycans on RBC membranes and the substrate properties play a significant role in driving and directing the membrane-particle assembly. These findings further the understanding of the dynamics between cellular membranes and nanoscale substrates and provide valuable information toward future development and characterization of cellular membrane-cloaked nanodevices.