细胞与发育生物学
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非热电磁场激活高 Tm 磁脂质体的按需药物释放

斯特凡尼娅·佩特拉利托

如今，纳米技术领域的研究和开发为各个领域提供了新颖的源泉。纳米科学和纳米粒子的产量也不例外。纳米颗粒只是纳米尺寸范围 (10−9 m) 的颗粒，通常尺寸 <100 nm。由于其非常小的尺寸和表面积特征，它们表现出独特的电子、光学和磁性特性，可用于药物输送。它们在药物递送领域也被称为纳米载体，它们是药物控释的新工具，因为它们可以满足成功治疗的两个最重要的标准，即空间放置和时间递送。基于磁性纳米粒子和脂质体之间的相互作用，已经建立了用于重金属检测的独特技术，这些纳米材料与细胞或其他生物分子之间的相互作用具有巨大的生物医学应用，包括细胞成像、细菌鉴定、癌症检测和药物输送。化学工程师团队利用插入脂质体中的现代纳米颗粒建立了一种精确输送药物的新系统，该脂质体可以通过非侵入性电磁场激活。

 

能量转移过程可以通过两个离散机制通过供体的失活和电子激发态受体的形​​成而发生。一是FRET，主要是通过空间机制发生的：需要供体的发射光谱与受体的吸收光谱重叠，由处于激发态的供体分子与受体之间的长期偶极-偶极相互作用获得。分子处于基态。另一种是DET，发生通过键合机制

 

Magnetic nanoparticles with superparamagnetic properties have attracted increased attention for applications in biomedicine, as they exhibit a strong magnetization only when an external magnetic field is applied. Magnetoliposomes (MLs) are the combination of liposomes with encapsulated magnetic nanoparticles. These hybrid nanocarriers have been showing significant biomedical application possibilities. However, it is essential that nanoparticles exhibit superparamagnetism, this causes nanoparticles to become susceptible to strong magnetization. When the magnetic field is applied, they orient toward this field, but do not retain permanent magnetization in the absence of magnetic field. SPIONs are small synthetic γ-Fe2O3 (maghemite), Fe3O4 (magnetite) or α-Fe2O3 (hermatite) particles with a core ranging from 10 nm to 100 nm in diameter. In addition, mixed oxides of iron with transition metal ions such as copper, cobalt, nickel, and manganese, are known to exhibit superparamagnetic properties and also fall into the category of SPIONs. However, magnetite and maghemite nanoparticles are the most widely used SPIONs in various biomedical applications.

 

The morphology of Fe2O3 nanoparticles has been known to be affected by several factors, including the reaction conditions and chemicals involved. In the presence of surfactants with bulky hydrocarbon chain structures, like oleylamine and adamantane amine, the steric hindrance exerted by surfactants has been shown to affect the shape of growing crystals of iron oxide during synthesis.11 The shape of magnetic nanoparticles has not been extensively studied as far as its effect on biodistribution of SPIONs is concern.

 

SPIONs have an organic or inorganic coating, on or within which a drug is loaded, and they are then guided by an external magnet to their target tissue. These particles exhibit the phenomenon of “superparamagnetism”, ie, on application of an external magnetic field, they become magnetized up to their saturation magnetization, and on removal of the magnetic field, they no longer exhibit any residual magnetic interaction. This property is size-dependent and generally arises when the size of nanoparticles is as low as 10–20 nm. At such a small size, these nanoparticles do not exhibit multiple domains as found in large magnets; on the other hand, they become a single magnetic domain and act as a “single super spin” that exhibits high magnetic susceptibility. Thus, on application of a magnetic field, these nanoparticles provide a stronger and more rapid magnetic response compared with bulk magnets with negligible remanence (residual magnetization) and coercivity.

 

This superparamagnetism, unique to nanoparticles, is very important for their use as drug delivery vehicles because these nanoparticles can literally drag drug molecules to their target site in the body under the influence of an applied magnet field. Moreover, once the applied magnetic field is removed, the magnetic particles retain no residual magnetism at room temperature and hence are unlikely to agglomerate (ie, they are easily dispersed), thus evading uptake by phagocytes and increasing their half-life in the circulation. Moreover, due to a negligible tendency to agglomerate, SPIONs pose no danger of thrombosis or blockage of blood capillaries.

 

The magnetic properties of super paramagnetic iron oxide nanoparticles (SPIONs)-based magnetoliposomes allow for alternative therapies through magnetically controlled drug delivery and hyperthermia. In this way they can be viewed as trigger-responsive carriers as they have the potential to act as "remote switch" that can turn on or off the effects of the therapeutics, based on the presence or absence of the stimulus. Recently, a pilot study has demonstrated the feasibility of smart controlled delivery through a magnetic field with intensity significantly lower than the ones usually reported in literature. In this way, a controlled release has been obtained through a magneto-nanomechanical approach without any macroscopic temperature increase. Specifically, signals generated by non-thermal alternating magnetic fields (AMFs) or non-thermal pulsed electromagnetic fields (PEMFs) were applied to high-transition temperature magnetoliposomes (high-Tm MLs) entrapping hydrophilic SPIONs, proving to be interesting and promising stimuli-controlled drug delivery systems