Modeling biomembranes and red blood cells by coarse-grained particle methods

In this work, the previously developed coarse-grained （CG） particle models for biomembranes and red blood cells （RBCs） are reviewed, and the advantages of the CG particle methods over the continuum and atomistic simulations for modeling biological phenomena are discussed. CG particle models can largely increase the length scale and time scale of atomistic simulations by eliminating the fast degrees of freedom while preserving the mesoscopic structures and properties of the simulated system. Moreover, CG particle models can be used to capture the microstructural alternations in diseased RBCs and simulate the topological changes of biomembranes and RBCs, which are the major challenges to the typical continuum representations of membranes and RBCs. The power and versatility of CG particle methods are demonstrated：through simulating the dynamical processes mvolving significant topological .changes e.g. lipid self-assembly vesicle fusion and membrane budding.

Effect of ultraviolet blood irradiation and oxygenation on nerve function and function of the red blood cell membrane pump in patients with acute cerebral infarction

BACKGROUND： Ultraviolet blood irradiation and oxygenation （UBIO） has obtained better clinical effect in treating acute cerebral infarction, but the mechanism underlying this effect remains unclear. OBJECTIVE： To observe the effect of UBIO on the nerve function and activities of K^＋-Na^＋-ATPase and Ca2^＋-Mg2^＋-ATPase activities on the red blood cell （RBC） membrane of patients with acute cerebral infarction. DESIGN： A randomized and controlled study.SETTING： Department of Neurology, Xiangfan Central Hospital.PARTICIPANTS： From January 2000 to December 2001, excluding those above 70 years old, 58 cases of 700 patients with acute cerebral infarction admitted in the Department of Neurology, Xiangfan Central Hospital, were recruited and divided into two groups according to the random number table： UBIO treated group （n=28）, including 17 males and 11 females, aged 40-68 years; and control group （n=30）, including 20 males and 10 females, aged 44-69 years. All the patients agreed to participate in the therapeutic program and detected items. The general informations were comparable without obvious differences between the two groups （P 〉 0.05）.METHODS： ① The patients in both groups received routine treatments, besides, those in the UBIO treated group were given UBIO treatment by using the XL-200 type therapeutic apparatus produced in Shijiazhuang, whose ultraviolet wave was set at 253.7 nm with the energy density of 0.568 J/m^2 per second, UBIO treatment started from the second day after admission, once every other day, with a single course consisting of 5-7 treatments. ② In the UBIO treated group, the venous blood was sampled before and after the first, third and the completion of the treatment course respectively, the venous blood was taken at each corresponding time point in the control group. After centrifugation of the blood at 10 000 rounds per minute, the RBC membrane was separated and then the activities of K^＋-Na^＋-ATPase and Ca2^＋-Mg2^＋-ATPase were detected by means of phosphorus determination.③ The nerve function was scored before and after treatment in both groups with European stroke scale, which included 13 items, the total score was 0-100 points, the higher the score, the better the nerve function. MAIN OUTCOME MEASURES ：①Score of European stroke scale before and after treatment in both groups.② Comparison of the activities of K^＋-Na^＋-ATPase and Ca2^＋-Mg2^＋-ATPase on RBC membrane between the two groups before treatment and after the first, third and the completion of the treatment. RESULTS： All the 58 patients with cerebral infarction were involved in the analysis of results.① The score of European stroke scale had no obvious difference between the two groups [（49.31±11.48）, （50.58±12.63）, P 〉 0.05], and it was obviously higher in the UBIO treated group than in the control group after treatment [84.66±13.75）, （77.05±11.17）, P 〈 0.05].②The activity of K^＋-Na^＋-ATPase on RBC membrane in the UBIO treated group was significantly increased after the first and third treatment as compared with before treatment [（31.56±19.25）, （27.64±15.83）, （17.67±13.83）, P 〈 0.01], it was still higher after the completion of the treatment than before treatment without obvious difference [（20.86±14.53）, P 〉 0.05]. After the first and third treatment, it was obviously higher in the UBIO treated group than in the control group [19.31±11.88）, （17.44±10.42）, P 〈 0.01]. ③ In the UBIO treated group, Ca2^＋-Mg2^＋-ATPase activity on RBC membrane significantly increased after the first treatment and remained higher than the pre-treatment level throughout the treatment [（27.49±14.72）, （17.41±4.82）, P 〈 0.01]. The activity of Ca2^＋-Mg2^＋-ATPase on RBC membrane was markedly higher in the UBIO treated group than in the control group after after the first, third and the completion of treatment respectively [（24.83±12.88）, （17.70±5.69）; （28.08±13.44）, （16.32±5.29）; （17.42±6.04）, P〈 0.05-0.01]. CONCLUSION： The effect of UBIO treatment against acute cerebral infarction may be mediated by the increased K^＋-Na^＋ ATPase and Ca2^＋-Mg2^＋-ATPase activities on RBC membrane, which enhances the RBC transformation ability so as to lower RBC aggregation and correct high blood viscosity.

RBC Membrane Camouflaged Semiconducting Polymer Nanoparticles for Near-Infrared Photoacoustic Imaging and Photothermal Therapy

Semiconducting conjugated polymer nanoparticles(SPNs)represent an emerging class of phototheranostic materi-als with great promise for cancer treatment.In this report,low-bandgap electron donoracceptor(DA)-conjugated SPNs with sur-face cloaked by red blood cell membrane(RBCM)are developed for highly e ective photoacoustic imaging and photothermal therapy.The resulting RBCM-coated SPN(SPN@RBCM)displays remarkable near-infrared light absorption and good photosta-bility,as well as high photothermal conver-sion e ciency for photoacoustic imaging and photothermal therapy.Particularly,due to the small size(<5 nm),SPN@RBCM has the advantages of deep tumor penetration and rapid clearance from the body with no appreciable toxicity.The RBCM endows the SPNs with prolonged systematic circulation time,less reticuloendothelial system uptake and reduced immune-recognition,hence improving tumor accumulation after intravenous injection,which provides strong photoacoustic signals and exerts excellent photothermal therapeutic e ects.Thus,this work provides a valuable paradigm for safe and highly e cient tumor pho-toacoustic imaging and photothermal therapy for further clinical translation.

Effect on Life Span and Membrane Protein in Red Blood Cells by Integrated Medicine Therapy on Chronic Aplastic Anemia

Objective: To explore the mechanism ofintegrated traditional Chinese and Westernmedicine (TCM--WM ) therapy on chronicaplastic anemia (CAA). Methods: The RBClife span of 30 normal human subjects and 30patients with CAA were measured by sir labelled technique before and after TCM--WMtherapy. The morphology and distribution ofRBC membrane protein granules were observed by freeze fracture etching and transmission electron microscope. Results: The halflife of erythrocytes (RBC TI/2)was shortenedin CAA cases and there was a significant difference compared to healthy control (P <0. 01). After therapy, the RBC life span prolonged and approached the normal level. Before treatment, there existed abnormal in morphology, decrease in amount and uneven indistribution of protein granules in protoplasmicface (PF) and extracellular face (EF) of RBCmembrane. After treatment, the protein granules of RBC membrane was improved and approached to control. Conclusions: The morphology, amount, quality and distribution ofRBC membrane protein granule were closelyrelated to its life span. The therapeutic effectof TCM--WM was better than that of WMalone and it had a function both in stabilizingmembrane protein and extending the RBC lifespan.

Cell Membrane-camouflaged Multi-functional Dendritic Large Pore Mesoporous Silica Nanoparticles for Combined Photothermal Therapy and Radiotherapy of Cancer

Combining photothermal therapy and radiotherapy(PTT-RT) with reducing tumor hypoxia acts as an important antitumor modality. However, it is a great challenge to realize photothermal therapy, radiotherapy and exogenous oxygen supply in one nanosystem. To realize a combination of the three functions, we fabricated a red blood cell membrane(RBCm)-camouflaged, red blood cell content(RBCc) and the copper sulfide(CuS) co-loaded dendritic large pore mesoporous silica nanoparticle(DLMSN/CuS/RBCc/ RBCm). The cell membrane coating endowed the nanoparticles with good stability in the physiological environment, and CuS allowed the nanoparticle exhibiting good photothermal and radiosensitization properties. RBCc loaded nanoparticle DLMSN/CuS/RBCc enhanced superior anti-tumor effect than DLMSN/CuS during combined PTT-RT therapy because the introduction of RBCc increased the exogenous oxygen supply. The in vitro study further demonstrated that the combination of photothermal therapy and radiotherapy induced superior antitumor efficacy than single therapy. Our work thus presents a unique multifunctional nanoscale platform favorable for combined PTT and RT.

Erythrocyte membrane-camouflaged nanoworms with on-demand antibiotic release for eradicating biofilms using near-infrared irradiation

The increase in the number of resistant bacteria caused by the abuse of antibiotics and the emergence of biofilms significantly reduce the effectiveness of antibiotics.Bacterial infections are detrimental to our life and health.To reduce the abuse of antibiotics and treat biofilm-related bacterial infections,a biomimetic nano-antibacterial system,RBCM-NW-G namely,that controls the release of antibiotics through near infrared was prepared.The hollow porous structure and the high surface activity of nanoworms are used to realize antibiotic loading,and then,biomimetics are applied with red blood cell membranes(RBCM).RBCM-NW-G,which retains the performance of RBCM,shows enhanced permeability and retention effects.Fluorescence imaging in mice showed the effective accumulation of RBCM-NW-G at the site of infection.In addition,the biomimetic nanoparticles showed a longer blood circulation time and good biocompatibility.Anti-biofilm test results showed damage to biofilms due to a photothermal effect and a highly efficient antibacterial performance under the synergy of the photothermal effect,silver iron,and antibiotics.Finally,by constructing a mouse infection model,the great potential of RBCM-NW-G in the treatment of in vivo infections was confirmed.

MicroRNA-208a silencing against myocardial ischemia/reperfusion injury mediated by reversibly camouflaged biomimetic nanocomplexes

MicroRNA-208a(miR-208a)plays critical roles in the severe fibrosis and heart failure post myocardial ischemia/reperfusion(IR)injury.MiR-208a inhibitor(mI)with complementary RNA sequence can silence the expression of miR-208a,while it is challenging to achieve efficient and myocardium-targeted delivery.Herein,biomimetic nanocomplexes(NCs)reversibly coated with red blood cell membrane(RM)were developed for the myocardial delivery of mI.To construct the NCs,membrane-penetrating helical polypeptide(PG)was first adopted to condense mI and form the cationic inner core,which subsequently adsorbed catalase(CAT)via electrostatic interaction followed by surface coating with RM.The membrane-coated NCs enabled prolonged blood circulation after systemic administration,and could accumulate in the injured myocardium via passive targeting.In the oxidative microenvironment of injured myocardium,CAT decomposed H_(2)O_(2)to produce O_(2)bubbles,which drove the shedding of the outer RM to expose the positively charged inner core,thus facilitated effective internalization by cardiac cells.Based on the combined contribution of mI-mediated miR-208a silencing and CAT-mediated alleviation of oxidative stress,NCs effectively ameliorated the myocardial microenvironment,hence reducing the infarct size as well as fibrosis and promoting recovery of cardiac functions.This study provides an effective strategy for the cytosolic delivery of nucleic acid cargoes in the myocardium,and it renders an enlightened approach to resolve the blood circulation/cell internalization dilemma of cell membrane-coated delivery systems.

Biomimetic selenium nanosystems for infectious wound healing

Bacteria-related wound infection and healing have been a major issue for patients and health-care systems for decades.The rise and evolution of effective treatment will result in significant benefits to human beings.In ad-dition to standard antibacterial drugs,a combination of nanoparticles(NPs)and biological membranes is widely applied as a novel antibacterial agent against infectious pathogens.In this paper,the red blood cell membrane-encapsulated selenium nanoparticles(R-SeNPs)were fabricated for infectious wound healing.The stability,the immune evading capability,and the internal circulation time of the R-SeNPs were notably enhanced compared with those of bare selenium nanoparticles(SeNPs).Moreover,in vivo studies demonstrated the outstanding per-formance of the R-SeNPs in infectious wound healing.The biomimetic selenium nanosystem demonstrated the benefits of the combination of nanotechnology and bionics design and will contribute to wound healing in the future.

Broad-spectrum and powerful neutralization of bacterial toxins by erythroliposomes with the help of macrophage uptake and degradation

Anti virulence strategy has been considered as one of the most promising approaches to combat drug-rcesistant bacterial infections.Porc-forming toxins(PFTs)are the largest class of bacterial toxins,inficting their virulence ffect through creating pores on the cell membrane.However,curent solutions for eliminating PFTs are mostly designed based on their molecular structure,requiring customized design for different interactions.In the present study,we employed erythroliposome(denoted as RM-PL),a biomimetic platform constructed by artificial lipid membranes and natural erythrocyle membranes,to necutralize different hemolytic PFTs regardless of their molecular structure.When tested with model PFTs,including a-hemolysin,listeriolysin O,and streptolysin O,RM-PL could completely inhibit toxin-induced hemolysis in a concentration-dependent manner.In vivo studies further confirmed that RM-PL.could eficiently neuralize various toxins and save animals'lives without causing damage to 0rgans or tissues.In addition,we explored the underlying mechanisms of this efficient detoxification ability and found that it was mainly macrophages in the spleen and the liver that took up RM-PL-absorbed toxins through a variety of endocytosis pathways and digested them in lysosomes.In summary,the biomimetic RM-PL presented a promising system for broad-spectrum and powerful toxin neutralization with a mech-anism of lysosome-mediaed loxin degradation.