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.

The emergence of antibiotic resistance has resulted in an increasing difficulty treating clinical infections associated with biofilms formation, one of the key processes contributed to enhance antibiotic resistance in return. With the rapid development of nanotechnology, a new way to overcome antibiotic resistance was opened up. Based on multiple properties especially antibacterial potential of MoS₂ nanosheets that have aroused wide attention, herein, a novel antimicrobial agent to combat resistant gram-positive Staphylococcus aureus (S. aureus) and gram-negative Salmonella was prepared using chitosan functionalized MoS₂ nanosheets loading tetracycline hydrochloride drugs (abbreviated to CM-TH). The antibacterial and anti-biofilm activities of CM-TH nanocomposites expressed a synergy effect that the combination of nanomaterials and antibiotics were more efficient than both alone did. Particularly, the MIC values were generally decreased by a factor of dozens, suggesting CM-TH may become a possible alternative to traditional antibiotics in disrupting the biofilms and further to overcome antibiotic resistance in treating medical diseases.

Cell membrane (CM) coating technology is increasingly being applied in nanomedicine, but the entire coating procedure including adsorption, rupture, and fusion is not completely understood. Previously, we showed that the majority of biomimetic nanoparticles (NPs) were only partially coated, but the mechanism underlying this partial coating remains unclear, which hinders the further improvement of the coating technique. Here, we show that partial coating is an intermediate state due to the adsorption of CM fragments or CM vesicles, the latter of which could eventually be ruptured under external force. Such partial coating is difficult to self-repair to achieve full coating due to the limited membrane fluidity. Building on our understanding of the detailed coating process, we develop a general approach for fixing the partial CM coating: external phospholipid is introduced as a helper to increase CM fluidity, promoting the final fusion of lipid patches. The NPs coated with this approach have a high ratio of full coating (~23%) and exhibit enhanced tumor targeting ability in comparison to the NPs coated traditionally (full coating ratio of ~6%). Our results provide a mechanistic basis for fixing partial CM coating towards enhancing tumor accumulation.

The aggregation behavior of dilute poly(1,1-dihydroperfluorooctyl acrylate-b-vinyl acetate) diblock copolymer in supercritical carbon dioxide (SCCO2) has been studied by using synchrotron smallangle X-ray scattering (SAXS) for the following two processes: an isothermal process with changes in pressure and a cooling process at a constant pressure. The above two processes also made it possible to compare the phase behavior of the solution at a constant SCCO2 density. The SAXS study, together with some light scattering experiments, shows that the phase behavior of the copolymer changes dramatically with experimental conditions in the SCCO2 solvent. The soluble solution was obtained at a low pressure of 180 bar with a corresponding SCCO2 density F ∼ 0.65 g/cm 3 and at a high pressure at 450 bar with F ∼ 0.90 g/cm 3 for the isothermal process at 65 °C. In the isothermal process, large aggregates exhibiting domain-packing structures were formed in the pressure range from 190 to 226 bar. Block copolymer micelles were observed at 243 bar and 65 °C, and the micellar behavior of the solution was then studied either by increasing the pressure at a constant temperature (65 °C) or by decreasing the temperature at a constant pressure (243 bar). The micellar size shows a similar dependence on the solution density for the above two processes. However, at a given SCCO 2 density, the phase behavior of the solution could be very different, including the species present and the micellar size, suggesting that the copolymer solution behavior in SCCO2 cannot be simplified only in terms of the SCCO2 density dependence, even though density is a crucial parameter which is intimately related to the solvent quality of SCCO2.