Optimal Halbach permanent magnet designs for maximally pulling and pushing nanoparticles

Optimization methods are presented to design Halbach arrays to maximize the forces applied on magnetic nanoparticles at deep tissue locations. In magnetic drug targeting, where magnets are used to focus therapeutic nanoparticles to disease locations, the sharp fall off of magnetic fields and forces with distances from magnets has limited the depth of targeting. Creating stronger forces at a depth by optimally designed Halbach arrays would allow treatment of a wider class of patients, e.g. patients with deeper tumors. The presented optimization methods are based on semi-definite quadratic programming, yield provably globally optimal Halbach designs in 2 and 3-dimensions, for maximal pull or push magnetic forces (stronger pull forces can collect nanoparticles against blood forces in deeper vessels; push forces can be used to inject particles into precise locations, e.g. into the inner ear). These Halbach designs, here tested in simulations of Maxwell's equations, significantly outperform benchmark magnets of the same size and strength. For example, a 3-dimensional 36 element 2000 cm³ volume optimal Halbach design yields a 5× greater force at a 10 cm depth compared to a uniformly magnetized magnet of the same size and strength. The designed arrays should be feasible to construct, as they have a similar strength (≤1 T), size (≤2000 cm³), and number of elements (≤36) as previously demonstrated arrays, and retain good performance for reasonable manufacturing errors (element magnetization direction errors ≤5°), thus yielding practical designs to improve magnetic drug targeting treatment depths.     

Inclusion of interactions in mathematical modelling of implant assisted magnetic drug targeting

Drug delivery technologies are an important area within biomedicine. Targeted drug delivery aims to reduce the undesired side effects of drug usage by directing or capturing the active agents near a desired site within the body. This is particularly beneficial in, for instance, cancer chemotherapy, where the side effects of general (systemic) drug administration can be severe.One approach to targeted drug delivery uses magnetic nanoparticles as the constituents of carriers for the desired active agent. Once injected into the body, the behaviour of these magnetic carriers can be influenced and controlled by magnetic fields. In implant assisted magnetic drug targeting systems a magnetic implant, typically a stent, wire or spherical seed can be used to target sites deep within the body as the implant acts as a focus for the resulting magnetic force. This can be easily understood as the force depends on the gradient of the magnetic field and the gradient near the implant is large.In designing such a system many factors need to be considered including physical factors such as the size and nature of the implants and carriers, and the fields required. Moreover, the range of applicability of these systems in terms of the regions of the vasculature system, from low blood velocity environments, such as capillary beds to higher velocity arteries, must be considered. Furthermore, assessment criteria for these systems are needed. Mathematical modelling and simulation has a valuable role to play in informing in vitro and in vivo experiments, leading to practical system design.Specifically, the implant assisted magnetic drug targeting systems of Avilés, Ebner and Ritter are considered within this review, and two dimensional mathematical modelling is performed using the open source C++ finite volume library OpenFOAM. In the first system treated, a large ferromagnetic particle is implanted into a capillary bed as a seed to aid collection of single domain nanoparticles (radius 20-100 nm). The Langevin function is used to calculate the magnetic moment of the particles, and the model is further adapted to treat the agglomeration of particles known to occur in these systems. This agglomeration can be attributed to interparticle interactions and here the magnetic dipole-dipole and hydrodynamic interactions for two mutually interacting nanoparticles are modelled, following Mikkelsen et al. who treated two particle interactions in microfluidic systems, with low magnetic field (0.05 T). The resulting predicted performance is found to both increase and decrease significantly depending on initial positions of the particles. Secondly, a ferromagnetic, coiled wire stent is implanted in a large arterial vessel. The magnetic dipole-dipole and hydrodynamic interactions for multiple particles are included. Different initial positions are considered and the system performance is assessed. Inclusion of these interactions yields predictions that are in closer agreement with the experimental results of Avilés et al. We conclude that the discrepancies between the non interacting theoretical predictions and the corresponding experimental results can (as suggested by Avilés et al.) be largely attributed to interparticle interactions and the consequent agglomeration.     

三嵌段共聚物EO20PO70EO20相分离行为的耗散粒子动力学模拟

采用耗散粒子动力学(DPD)方法研究了嵌段共聚物EO₂₀PO₇₀EO₂₀(P123)在水、乙醇/水溶液及二氧化硅溶胶体系中的相分离行为. 不同质量分数的P123在水溶液中共形成4种相分离状态: 球状胶束(10%); 椭球胶束(20%)、棒状胶束(30%)和三维立方胶束(50%). 在模板剂质量分数为10%的乙醇/水溶液中, 模板剂胶束稳定性随着乙醇含量的增加而变差. 在二氧化硅溶胶体系中, 模板剂质量分数低于5%时无胶束形成; 模板剂质量分数增至10%时, P123发生相分离形成三维球状胶束; 随着模板剂质量分数的进一步增加, 模板剂分子夹含着水分子形成三维椭球状结构(20%)、三维立方结构(40%)和层状结构(60%). 模拟结果与实验结果一致, 说明DPD模拟可以从计算角度推测模板剂对介孔材料结构的影响.     

导弹逼近光电告警系统的新进展

综述国外导弹逼近红外告警和紫外告警系统的最新进展。     

基于改进混合蛙跳算法的CVRP求解

该文提出基于实数编码模式的混合蛙跳算法(Shuffled Frog Leaping Algorithm,SFLA)求解容量约束车辆路径问题(Capacitated Vehicle Routing Problem,CVRP);把具有极强局部搜索能力的幂律极值动力学优化(Power Law Extremal Optimization,-EO)融合于SFLA,针对CVRP对-EO过程进行设计和改进。改进的-EO采用新颖的组元适应度计算方法;采用幂律概率分布来挑选需要变异的组元;根据最邻近城市表,采用幂律概率分布挑选变异组元的最佳邻近城市,执行线路间或线路内的变异。求解测试库中的实例,证明该改进算法有效。     

Mechanism Study on Nanoparticle Negative Surface Charge Modification by Ascorbyl Palmitate and Its Improvement of Tumor Targeting Ability

Surface charge polarity and density influence the immune clearance and cellular uptake of intravenously administered lipid nanoparticles (LNPs), thus determining the efficiency of their delivery to the target. Here, we modified the surface charge with ascorbyl palmitate (AsP) used as a negatively charged lipid. AsP-PC-LNPs were prepared by dispersion and ultrasonication of AsP and phosphatidylcholine (PC) composite films at various ratios. AsP inserted into the PC film with its polar head outward. The pK_a for AsP was 4.34, and its ion form conferred the LNPs with negative surface charge. Zeta potentials were correlated with the amount and distribution of AsP on the LNPs surface. DSC, Raman and FTIR spectra, and molecular dynamics simulations disclosed that AsP distributed homogeneously in PC at 1–8% (w/w), and there were strong hydrogen bonds between the polar heads of AsP and PC (PO²⁻), which favored LNPs’ stability. But at AsP:PC > 8% (w/w), the excessive AsP changed the interaction modes between AsP and PC. The AsP–PC composite films became inhomogeneous, and their phase transition behaviors and Raman and FTIR spectra were altered. Our results clarified the mechanism of surface charge modification by AsP and provided a rational use of AsP as a charged lipid to modify LNP surface properties in targeted drug delivery systems. Furthermore, AsP–PC composites were used as phospholipid-based biological membranes to prepare paclitaxel-loaded LNPs, which had stable surface negative charge, better tumor targeting and tumor inhibitory effects.     

Nano-Oncologicals: A Tortoise Trail Reaching New Avenues

Research efforts towards cancer therapeutics have resulted in the development of a variety of pharmacological molecules, including small synthetic molecules and biological drugs (RNA-based therapies and monoclonal antibodies—mAbs), intended to target tumor or immune-related cells, or their signaling mediators. The majority of them present important biopharmaceutical problems related to their difficulties for overcoming biological barriers and reach their targets. Nanotechnology has been, for more than 60 years, trying to solve these problems. As knowledge in drug discovery, molecular biology, and biomaterials advances, there has been significant progress in the adequate design of nanodelivery strategies that may significantly contribute to the exploitation of the new therapies. This review provides a critical overview of the current potential of nanotechnology to solve problems associated with the different categories of drugs. Starting with the general concept of passive and active targeting, it presents the distinct advantages that delivery technologies have shown to date for improving the therapeutic outcome of small drugs with cytotoxic activity, RNA- and mAb-based therapies. Moreover, it precisely describes the benefits of combining immunotherapies and nanotechnology. The most advanced technologies are put into perspective in relation to their translational pathway and the future avenues for nano-oncologicals.     

Distinguishable Targeting of Non-Small Cell Lung Cancer Using Hyaluronan Functionalized Platinum Nanoclusters and Their Inhibition Behaviors of Proliferation,Invasion, Migration

Lung cancer is the leading cause of cancer deaths worldwide and most cancer patients receiving conventional chemotherapy suffer from severe side effects due to the non-selective effects of chemotherapeutic drugs on normal cells. Targeted nanomaterials can obtain excellent accumulation at the tumor site through their active or passive targeting mechanisms, thereby reducing the toxicity of the drugs in various ways. In this study, hyaluronic acid (HA) which could specifically bind to CD44 on the surface of tumor cells, was used to modify amine-caged platinum nanoclusters (Pt NCs-NH₂) to obtain targeting HA-Pt NCs-NH₂. Based on the differential expression of CD44 on the surface of three lung cells (non-small cell lung cancer cell H1299, small cell lung cancer cell H446, and embryonic lung fibroblast HFL1), HA-Pt NCs-NH₂ can differentially enter the three cells and achieve their targeting of non-small cell lung cancer cell (NSCLC) cells. Pt NCs significantly inhibited the proliferation, migration and invasion of NSCLC cells and induced their apoptosis in comparison of classical cisplatin and carboplatin, showing a bright future in early diagnosis and treatment of NSCLC.     

The versatility of carbohydrates in antimicrobial applications

The worsening situation of global drug resistance is urgently demanding for novel antimicrobial agents. Considerable efforts have been concentrated on developing new antibacterial therapies with new mode of actions, exerting no selective pressure on bacterial mutation, and minimizing toxicity to host cells. In this context, active targeting can greatly contribute to selectivity between pathogens and mammalian cells in which carbohydrates, playing important roles in numerous biological processes, can be employed as targeting ligands or “trojan horse.” This short account has discussed the recent results of carbohydrate-based antimicrobial agents developed by our group. Other excellent works by other scientists and possible directions in the future are also discussed.     

Ultrasound assisted formation of essential oil nanoemulsions: Emerging alternative for Culex pipiens pipiens Say (Diptera: Culicidae) and Plodia interpunctella Hübner (Lepidoptera: Pyralidae) management

Over the last years, nanotechnology has contributed to the development of new botanical insecticides formulations based on essential oils (EO), which are safe for the human health and the environment. Nanoemulsions (NEs) can enhance the bioactivity of the EO to prevent the premature volatility and degradation of the active ingredients. In our work, geranium EO (Geranium maculatum L.) was used to develop micro and nanoemulsions adding Tween 80 as surfactant. For NEs formulation, ultrasound was applied and the physicochemical and ultrasound parameters were optimized: oil: surfactant ratio = 1:2, ultrasound power = 65 W, sonication time = 2 min, cycles = 30 on/20 off and ultrasonic probe distance = 3.7 cm. The NEs obtained had 13.58 nm and polydisperse index (PDI) values of 0.069. They were stored at 25 °C and were stable for 60 days.The present study also demonstrated the potential of NEs to enhance the toxicity of geranium EO against larvae of Culex pipiens pipiens (EO LC₅₀ = 80.97 ppm, NEs LC₅₀ = 48.27 ppm) and Plodia interpunctella (EO + β-cypermethrin LD₅₀ = 0.16 μg larvae⁻¹, NEs + β-cypermethrin LD₅₀ = 0.07 μg larvae⁻¹). Overall, our findings pointed out that NEs can increase twofold the insecticidal efficacy of EO, and thus, they can be considered further for the development of botanical insecticides.