Department of Biology-Chemistry, Advanced Environmental Research Laboratory, West University of Timisoara, Timișoara, 300086, Romania.
Molecules. 2020 Oct 16;25(20):4758. doi: 10.3390/molecules25204758.
Chitosan is a polymer that is extensively used to prepare nanoparticles (NPs) with tailored properties for applications in many fields of human activities. Among them, targeted drug delivery, especially when cancer therapy is the main interest, is a major application of chitosan-based NPs. Due to its positive charges, chitosan is used to produce the core of the NPs or to cover NPs made from other types of polymers, both strategies aiming to protect the carried drug until NPs reach the target sites and to facilitate the uptake and drug delivery into these cells. A major challenge in the design of these chitosan-based NPs is the formation of a protein corona (PC) upon contact with biological fluids. The composition of the PC can, to some extent, be modulated depending on the size, shape, electrical charge and hydrophobic / hydrophilic characteristics of the NPs. According to the composition of the biological fluids that have to be crossed during the journey of the drug-loaded NPs towards the target cells, the surface of these particles can be changed by covering their core with various types of polymers or with functionalized polymers carrying some special molecules, that will preferentially adsorb some proteins in their PC. The PC's composition may change by continuous processes of adsorption and desorption, depending on the affinity of these proteins for the chemical structure of the surface of NPs. Beside these, in designing the targeted drug delivery NPs one can take into account their toxicity, initiation of an immune response, participation (enhancement or inhibition) in certain metabolic pathways or chemical processes like reactive oxygen species, type of endocytosis of target cells, and many others. There are cases in which these processes seem to require antagonistic properties of nanoparticles. Products that show good behavior in cell cultures may lead to poor in vivo results, when the composition of the formed PC is totally different. This paper reviews the physico-chemical properties, cellular uptake and drug delivery applications of chitosan-based nanoparticles, specifying the factors that contribute to the success of the targeted drug delivery. Furthermore, we highlight the role of the protein corona formed around the NP in its intercellular fate.
壳聚糖是一种广泛用于制备具有特定性质纳米粒子(NPs)的聚合物,这些纳米粒子在人类活动的许多领域都有应用。其中,靶向药物输送,特别是当癌症治疗是主要关注点时,是壳聚糖基 NPs 的主要应用之一。由于其正电荷,壳聚糖被用于制备 NPs 的核心或覆盖由其他类型聚合物制成的 NPs,这两种策略都是旨在保护携带的药物直到 NPs 到达靶位点,并促进这些细胞的摄取和药物输送。在设计这些壳聚糖基 NPs 时,一个主要挑战是在与生物流体接触时形成蛋白质冠(PC)。PC 的组成在一定程度上可以根据 NPs 的大小、形状、电荷和疏水性/亲水性特征进行调节。根据药物负载 NPs 在向靶细胞输送过程中必须穿过的生物流体的组成,可以通过用各种类型的聚合物或带有某些特殊分子的功能化聚合物覆盖它们的核心来改变这些颗粒的表面,这些特殊分子将优先在它们的 PC 中吸附某些蛋白质。PC 的组成可能会通过吸附和解吸的连续过程发生变化,这取决于这些蛋白质对 NPs 表面化学结构的亲和力。除此之外,在设计靶向药物输送 NPs 时,人们可以考虑它们的毒性、免疫反应的启动、参与(增强或抑制)某些代谢途径或化学过程,如活性氧物种、靶细胞的内吞作用类型,以及许多其他因素。在某些情况下,这些过程似乎需要纳米粒子的拮抗特性。在细胞培养中表现出良好行为的产品在形成的 PC 完全不同的情况下可能会导致体内结果不佳。本文综述了壳聚糖基纳米粒子的物理化学性质、细胞摄取和药物输送应用,指出了有助于靶向药物输送成功的因素。此外,我们还强调了 NP 周围形成的蛋白质冠在其细胞内命运中的作用。
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