Biomimetic cell membrane-coated nanoparticles (CM-NPs) with superior biochemical properties have been broadly utilized for various biomedical applications. Currently, researchers primarily focus on using ultrasonic treatment and mechanical extrusion to improve the synthesis of CM-NPs. In this work, we demonstrate that microfluidic electroporation can effectively facilitate the synthesis of CM-NPs. To test it, FeO magnetic nanoparticles (MNs) and red blood cell membrane-derived vesicles (RBC-vesicles) are infused into a microfluidic device. When the mixture of MNs and RBC-vesicles flow through the electroporation zone, the electric pulses can effectively promote the entry of MNs into RBC-vesicles. After that, the resulting RBC membrane-capped MNs (RBC-MNs) are collected from the chip and injected into experimental animals to test the in vivo performance. Owing to the superior magnetic and photothermal properties of the MN cores and the long blood circulation characteristic of the RBC membrane shells, core-shell RBC-MNs were used for enhanced tumor magnetic resonance imaging (MRI) and photothermal therapy (PTT). Due to the completer cell membrane coating, RBC-MNs prepared by microfluidic electroporation strategy exhibit significantly better treatment effect than the one fabricated by conventional extrusion. We believe the combination of microfluidic electroporation and CM-NPs provides an insight into the synthesis of bioinpired nanoparticles to improve cancer diagnosis and therapy.

Many smart materials in bioengineering, nanotechnology and medicine allow the storage and release of encapsulated drugs on demand at a specific location by an external stimulus. Owing to their versatility in material selection, polyelectrolyte multilayers are very promising systems in the development of microencapsulation technologies with permeation control governed by variations in the environmental conditions. Here, organometallic polyelectrolyte multilayer capsules, composed of polyanions and polycations of poly(ferrocenylsilane) (PFS), are introduced. Their preparation involved layer-by-layer self-assembly onto colloidal templates followed by core removal. PFS polyelectrolytes feature redox-active ferrocene units in the main chain. Incorporation of PFS into the capsule walls allowed us to explore the effects of a new stimulus, that is, changing the redox state, on capsule wall permeability. The permeability of these capsules could be sensitively tuned via chemical oxidation, resulting in a fast capsule expansion accompanied by a drastic permeability increase in response to a very small trigger. The substantial swelling could be suppressed by the application of an additional coating bearing common redox-inert species of poly(styrene sulfonate) (PSS(-)) and poly(allylamine hydrochloride) (PAH(+)) on the outer wall of the capsules. Hence, we obtained a unique capsule system with redox-controlled permeability and swellability with a high application potential in materials as well as in bioscience.

Controlled delivery of protein therapeutics remains a challenge. Here, the inclusion of diselenide-bond-containing organosilica moieties into the framework of silica to fabricate biodegradable mesoporous silica nanoparticles (MSNs) with oxidative and redox dual-responsiveness is reported. These diselenide-bridged MSNs can encapsulate cytotoxic RNase A into the 8-10 nm internal pores via electrostatic interaction and release the payload via a matrix-degradation controlled mechanism upon exposure to oxidative or redox conditions. After surface cloaking with cancer-cell-derived membrane fragments, these bioinspired RNase A-loaded MSNs exhibit homologous targeting and immune-invasion characteristics inherited from the source cancer cells. The efficient in vitro and in vivo anti-cancer performance, which includes increased blood circulation time and enhanced tumor accumulation along with low toxicity, suggests that these cell-membrane-coated, dual-responsive degradable MSNs represent a promising platform for the delivery of bio-macromolecules such as protein and nucleic acid therapeutics.