Optimization of critical parameters for coating of polymeric nanoparticles with plasma membrane vesicles by sonication

Top-down functionalization of nanoparticles with cellular membranes imparts nanoparticles with enhanced bio-interfacing capabilities. Initial methods for membrane coating involved physical co-extrusion of nanoparticles and membrane vesicles through a porous membrane; however, recent works employ sonication as the disruptive force to reform membranes around the surface of nanoparticles. Although sonication is widely used, there remains a paucity of information on the effects of sonication variables on coating efficiency, leading to inconsistent membrane coating across studies. In this work, we present a systematic analysis of the sonication parameters that influence the membrane coating. The results showed that sonication amplitude, time, temperature, membrane ratio, sample volume, and density need to be considered in order to optimize membrane coating of polymeric nanoparticles.

Cell membrane coating integrity affects the internalization mechanism of biomimetic nanoparticles

Cell membrane coated nanoparticles (NPs) have recently been recognized as attractive nanomedical tools because of their unique properties such as immune escape, long blood circulation time, specific molecular recognition and cell targeting. However, the integrity of the cell membrane coating on NPs, a key metrics related to the quality of these biomimetic-systems and their resulting biomedical function, has remained largely unexplored. Here, we report a fluorescence quenching assay to probe the integrity of cell membrane coating. In contradiction to the common assumption of perfect coating, we uncover that up to 90% of the biomimetic NPs are only partially coated. Using in vitro homologous targeting studies, we demonstrate that partially coated NPs could still be internalized by the target cells. By combining molecular simulations with experimental analysis, we further identify an endocytic entry mechanism for these NPs. We unravel that NPs with a high coating degree (≥50%) enter the cells individually, whereas the NPs with a low coating degree (<50%) need to aggregate together before internalization. This quantitative method and the fundamental understanding of how cell membrane coated NPs enter the cells will enhance the rational designing of biomimetic nanosystems and pave the way for more effective cancer nanomedicine.

A Novel Biomimetic Nanoprobe as a Photoacoustic Contrast Agent

Specific detection of tumors is of pivotal importance to cancer prevention and therapy yet a big challenge. Photoacoustic imaging (PAI) as an emerging non-invasive modality has shown great potential in biomedical and clinical applications. The performance of PAI largely depends on the light-absorption coefficient of the imaged tissue and the PAI contrast agent being used, either endogenously or exogenously. The exogenous contrast agents developed so far have greatly helped to improve PAI, but still have some limitations, such as lack of targeting capacity and easy clearance by the host immune system. Herein, we fabricated a biomimetic nanoprobe with cell membrane coating as a novel PAI contrast agent, namely, MPD [membrane-coated poly(lactic-co-glycolic acid) (PLGA)/dye]. In brief, the organic dye 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricarbocyanine iodide (DiR) was encapsulated by the Food and Drug Administration–approved polymer, poly(lactic-co-glycolic acid) (PLGA), to form polymer nanoparticles by emulsification. The nanoparticles are further coated with the cancer cell membrane to form MPD. MPD has outstanding biocompatibility, tumor specificity, and in vivo stability. Thus, MPD is a versatile NIR-I theranostic nanoplatform for PAI-guided cancer diagnosis and therapy.

Biomimetic nanoparticles enabled by cascade cell membrane coating for direct cross-priming of T cells

Despite the activation of T lymphocytes by antigen-presenting cells is responsible for eliciting antigen-specific immune responses, their crosstalking suffers from temporospatial limitations and endogenous influencing factors, which restrict the generation of a strong antitumor immunity. Here, we describe the manipulation of cross-priming of T cells using biomimetic nanoparticles (BNs) enabled by cascade cell membrane coating. BNs are resulted from coating nanoparticulate substrates with cell membranes extracted from dendritic cells (DCs) that are pre-pulsed with cancer cell membrane-coated nanoparticles. With a DC membrane that presents an array of cancer cell membrane antigen epitopes, BNs inherit intrinsic membrane function of DCs. Strikingly, BNs can directly cross-prime T cells and provoke robust yet antigen-specific antitumor responses in multiple mouse models. Combination with clinical anti-programmed death-1 antibodies demonstrates a practical way of BNs to achieve desirable tumor regression and survival rate. This work spotlights the impact of nanoparticles on direct cross-priming of T cells and supports a unique yet modulate platform for boosting an effective adaptive immunity for immunotherapy.

Recent Advances of Cell Membrane Coated Nanoparticles in Treating Cardiovascular Disorders

Cardiovascular diseases (CVDs) are the leading cause of death worldwide, causing approximately 17.9 million deaths annually, an estimated 31% of all deaths, according to the WHO. CVDs are essentially rooted in atherosclerosis and are clinically classified into coronary heart disease, stroke and peripheral vascular disorders. Current clinical interventions include early diagnosis, the insertion of stents, and long-term preventive therapy. However, clinical diagnostic and therapeutic tools are subject to a number of limitations including, but not limited to, potential toxicity induced by contrast agents and unexpected bleeding caused by anti-platelet drugs. Nanomedicine has achieved great advancements in biomedical area. Among them, cell membrane coated nanoparticles, denoted as CMCNPs, have acquired enormous expectations due to their biomimetic properties. Such membrane coating technology not only helps avoid immune clearance, but also endows nanoparticles with diverse cellular and functional mimicry. In this review, we will describe the superiorities of CMCNPs in treating cardiovascular diseases and their potentials in optimizing current clinical managements.