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

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 pH. 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.