Predicting optoacoustic spectral behaviour of human erythrocytes, stomatocytes and echinocytes using a modified Green's function method.

Optoacoustic (OA) spectral properties of various sources mimicking normal and pathological red blood cells (RBCs) have been studied. The shapes of normal RBC and cells suffering from stomatocytosis (denoted by ST) were generated using mathematical models. However, the shape corresponding to the cells affected by echinocytosis (referred to as ET) was constructed by uniformly distributing half prolate spheroids on a central spherical object. The OA field emitted by an acoustically inhomogeneous source was calculated for a wide acoustic frequency bandwidth (1-1500 MHz with an increment 5 MHz) by solving the time-independent wave equation employing a modified Green's function approach. The OA spectra averaged over 200 orientations for normal RBC and STs demonstrate similar features (one minimum occurring nearly at 906 MHz). The same graphs for ETs are remarkably different from that of normal RBC and exhibit better match with that of a spherical RBC (first minimum appearing at around 425 MHz). The spectral features of ETs above 425 MHz may enable us to differentiate diseased cells (echinocytosis) from normal RBCs.

Hybrid Biodegradable Nanomotors through Compartmentalized Synthesis.

Designer particles that are embued with nanomachinery for autonomous motion have great potential for biomedical applications; however, their development is highly demanding with respect to biodegradability/compatibility. Previously, biodegradable propulsive machinery based on enzymes has been presented. However, enzymes are highly susceptible to proteolysis and deactivation in biological milieu. Biodegradable hybrid nanomotors powered by catalytic inorganic nanoparticles provide a proteolytically stable alternative to those based upon enzymes. Herein we describe the assembly of hybrid biodegradable nanomotors capable of transducing chemical energy into motion. Such nanomotors are constructed through a process of compartmentalized synthesis of inorganic MnO2 nanoparticles (MnPs) within the cavity of organic stomatocytes. We show that the nanomotors remain active in cellular environments and do not compromise cell viability. Effective tumor penetration of hybrid nanomotors is also demonstrated in proof-of-principle experiments. Overall, this work represents a new prospect for engineering of nanomotors that can retain their functionality within biological contexts.

Stomatocyte in Stomatocyte: A New Shape of Polymersome Induced via Chemical-Addition Methodology.

Accurate control of the shape transformation of polymersome is an important and interesting challenge that spans across disciplines such as nanomedicine and nanomachine. Here, we report a fast and facile methodology of shape manipulation of polymersome via out-of-equilibrium polymer self-assembly and shape change by chemical addition of additives. Due to its increased permeability, hydrophilicity, and fusogenic properties, poly(ethylene oxide) was selected as the additive for bringing the system out of equilibrium via fast addition into the polymersome organic solution. A new shape, stomatocyte-in-stomatocyte (sto-in-sto), is obtained for the first time. Moreover, fast shape transformation within less than 1 min to other relevant shapes such as stomatocyte and large compound vesicles was also obtained and accurately controlled in a uniform dispersion. This methodology is demonstrated as a general strategy with which to push the assembly further out of equilibrium to generate unusual nanostructures in a controllable and fast manner.

Elastic energy of the discocyte-stomatocyte transformation.

The aim of this study is to calculate the membrane elastic energy for the different shapes observed in the discocyte-stomatocyte sequence. This analysis can provide a better quantitative understanding of the hypothesis put forward over the last decades to explain how red blood cells produce and maintain their typical shape. For this purpose, we use geometrical models based on parametric equations. The energy model considered for the elastic properties of RBC membrane includes the local and nonlocal resistance effects of the bilayer to bending. In particular, the results confirm the discocyte as the lowest energy value configuration among the sets of different red blood cell deformations considered in the sequence.

Synthetic Membrane Shaper for Controlled Liposome Deformation.

Shape defines the structure and function of cellular membranes. In cell division, the cell membrane deforms into a "dumbbell" shape, while organelles such as the autophagosome exhibit "stomatocyte" shapes. Bottom-up in vitro reconstitution of protein machineries that stabilize or resolve the membrane necks in such deformed liposome structures is of considerable interest to characterize their function. Here we develop a DNA-nanotechnology-based approach that we call the synthetic membrane shaper (SMS), where cholesterol-linked DNA structures attach to the liposome membrane to reproducibly generate high yields of stomatocytes and dumbbells. In silico simulations confirm the shape-stabilizing role of the SMS. We show that the SMS is fully compatible with protein reconstitution by assembling bacterial divisome proteins (DynaminA, FtsZ:ZipA) at the catenoidal neck of these membrane structures. The SMS approach provides a general tool for studying protein binding to complex membrane geometries that will greatly benefit synthetic cell research.

Magnetic stomatocyte-like nanomotor as photosensitizer carrier for photodynamic therapy based cancer treatment.

Amphiphilic block copolymer can self-assemble to stomatocyte-like structure as drug delivery carrier. Photodynamic therapy (PDT) is an emerging modality for cancer treatment. However, PDT has various problems, such as weak tumor accumulation ability of photosensitizers (PSs), short lifetime of singlet oxygen (1O2, main reactive oxygen species in PDT) and tumor hypoxia microenvironment, to restrict its therapeutic efficacy. To convey PSs to tumor tissues and improve PDT efficacy, iron oxide nanoparticles (IONPs) were loaded inside the self-assembly stomatocytes-like structure of poly(ethylene glycol) block polystyrene (PEG-b-PS) as nanomotors (IONPs loaded stomatocytes nanomotors, denoted IS-NMs) for PS (zinc phthalocyanine, ZnPc) delivery. The hybrid nanomotors (iron oxide nanoparticles loaded stomatocytes@ZnPc nanomotors, denoted ISP-NMs) can be gathered in tumor tissues under magnetic field owing to magnetism of IONPs. After been trapped by cancer cells, IONPs can catalyze decomposition of endogenous H2O2 to generate O2 as propelling force for ISP-NMs movement. The motion characteristics of ISP-NMs expanded the distribution of ZnPc to enlarge ROS reactive distribution and enhance the activity of PDT. And the generated O2 can be supplied for PDT process to ensure its high-performance. Furthermore, ISP-NMs have nuclear magnetic resonance imaging (MRI) function since IONPs are efficient T2 contrast agent.

Interaction of injectable neurotropic drugs with the red cell membrane.

The normal red blood cell (RBC) shape is a biconcave discocyte. An intercalation of a drug in the outer half of the membrane lipid bilayer leads to echinocytosis, an intercalation in the inner half to stomatocytosis. We have used the shape transforming capacity of RBCs as a model to analyse the membrane interaction potential of various neurotropic drugs. Chlorpromazine, clomipramine, citalopram, clonazepam, and diazepam induced a reversible stomatocytosis, phenytoin induced echinocytosis, while the anticonvulsants levetiracetam, valproic acid and phenobarbital had no effect. This diversity of RBC shape transformations suggests that the pharmacological action is not linked to the membrane interaction. We conclude that this simple RBC shape transformation assay could be a useful tool to screen for potential drug interactions with cell membranes.