层层自组装纳米药物载体在癌症治疗中的研究进展

Research progress of layer-by-layer self-assembled nanocarriers for cancer treatment

层层组装制备过程简单,适用基材广,可通过组装基元和超分子组装驱动力等参数的调控和组合,衍生出众多的超分子组装结构和功能,发展为最有潜力的表面可控制备、修饰技术.层层自组装技术近些年来在生物医学领域研究突出,本文主要概括了层层自组装纳米药物载体共载两种治疗制剂,以及不同响应型和靶向功能的纳米药物载体的构建及功能,并在此基础上探讨了其在抗癌治疗的发展前景.

In the course of cancer treatment, strong side effects of drugs will bring great suffering to the patients, and the drug is difficult to be enriched in the lesion site and greatly reduce the effect of drugs. It is very important to design a suitable drug carrier for the treatment of cancer. The preparation method of ultrathin films by alternating electrostatic adsorption was reported in 1966. In 1991, the technology of alternating electrostatic deposition was presented, and applied in the preparation of ultrathin film of polyelectrolyte and small organic molecules. Then it has been widely used for surface modification of biomaterials in the field of chemistry and biomedicine. In recent years, the studies of the layer-by-layer self-assembled（LbL） technology in the field of cancer therapy are highlighted, and it has potential as a new drug carrier in the treatment of cancer. LbL has the advantages of simple preparation process, wide applicable material, regulation and combination of driving force and other parameters through a variety of assembled primitives and a variety of supramolecular assemblies, which are benefit for producing numerous supramolecular assembled structures. It has become the most promising surficial controllable preparation and modification technology. Most of the compounds could be used as an assembled film, which could be charged by adjusting the p H. The drug release behavior can be controlled by combining the different properties of multilayer films. This article mainly summarized the recent research progress of LbL drug delivery system delivering drug, controllable release, targeting and multifunction in the treatment of cancer. The different loading methods for hydrophilic and hydrophobic drugs were introduced, as well as the structural advantages of co-delivering two kinds of therapeutic agents, including two chemotherapeutic drugs, two genes, one chemotherapy drug and one gene. LbL nano-drug carriers achieve drug controllable release by utilizing the structures and assembling stimuli-responsive polyelectrolyte, including pH, temperature, light and other stimuli-responsive polyelectrolyte. The targeted function of LbL nanoparticles could be divided into active and passive target. The passive target has been determined by the size of carriers, and the active target has been determined by connecting the target group, including folate, aptamer, RGD peptide and so on. The multifunctional LbL nano-drug carrier system is more reasonable for releasing drugs in structure, so as to achieve the purpose of maximizing the therapeutic effect. LbL drug carriers have unique advantage in providing a more controllable release compared to other delivery methods. LbL nanoparticle and nanocapsule could load at least two kinds of drugs into the substrate and the multilayer film. The drug-loading rate could be accurately controlled by using drug as an assembled component, and it could precisely regulate assembled components, showing great potential for next generation drug-delivery systems. There are some challenges and overcome, for example for further applications, for example, how to improve the mechanical performance in order to ensure the stability for long time in vivo circulation. The downstream cellar responses and signaling pathways during the interactions of LbL systems with cells or organs require further investigation. We believe that the LbL nano-drug delivery system will provide a novel approach for clinical therapeutic applications, with tunable sustained release of multiple drugs.