Poly(A) Functionalized Mesoporous Silica Nanoparticles For Drug Controlled Release And Tumor Therapy

With the development of nanotechnology, the functionalized nanomaterials have tremendous potential in tumor therapy. On the one hand, functional nanocarriers can improve the targeted transport efficiency and reduce the side effects by realizing the controlled release of drugs. On the other hand, they can solve the limitations of the single-mode treatment and enhance the therapy efficiency via a multi-mode treatment. Mesoporous silica nanoparticles (MSN) have been widely used to construct drug controlled release system due to its large package of loading, adjustable aperture, chemical stability, biocompatibility and other advantages. Nucleic acid, as a kind of biological macromolecules with the significant advantages for their remarkable molecular self-recognition capabilities, unique structural motif, good biocompatibility, easily modified and other advantages, has been used as a popular nanoscopic cap grafted onto MSN to control the opening and closing of the pore. Poly adenine (poly(A)), a common nucleic acid constructs in eukaryotes, is closely related to several life activity. It can protect mRNA from the degradation of exonuclease, enhance the stability of mRNA, and has a significant impact on the transport and translation of mRNA. Research shows that poly(A) can specifically combined with the isoquinoline alkaloids (such as coralyne) by hydrogen bonding. Under the low-pH or high-temperature condition, the hydrogen binding force declines, leading to the dehybridization of the cooperative binding structure. We expect these properties can be used in the gated design of MSN and the treatment of tumor. This essay carried out the research of drug control release systems based on the poly(A) functionalized MSN, following the two parts:1. pH responsive controlled release system based on poly(A) capped MSN nanoparticles for antitumorWe designed a pH controlled release system based on the poly(A) functionalized MSN. Coralyne could result in the particular combination of poly(A) and be used for cancer chemotherapy. In the design, alkyne-modified poly(A) was immobilized on the surface of MSN by a click chemistry approach. Coralyne was loaded by diffusion at a high temperature and then cooled to room temperature. The specific combination between coralyne and poly(A), was used as a nanoscopic cap of coralyne@poly(A)-MSN. The pores were well blocked because the particular binding was stable at neutral pH buffer. Under the acidic conditions, the hydrogen bonding force was getting weak, leading to the pores opening. We studied the intracellular behavior and the cytotoxicity by using laser confocal scanning microscopy and MTT experiments, respectively. The experiment results indicated the drug delivery system could be located in the lysosomes after internalized by cells, leading to drug controlled release and significant cytotoxicity.2. Co-loading of coralyne and indocyanine green into the adenine DNA functionalized mesoporous silica nanoparticles for the pH-and near-infrared-responsive chemothermal treatment of cancer cellsBased on the above work, we developed a controlled release system by co-loading coralyne and indocyanine green (ICG) into poly(A) functionalized MSN, witch could response to pH and NIR light. In this design, alkyne-modified poly(A) was immobilized at the pore mouth of MSN by a click chemistry approach. Coralyne and ICG were co-loaded by diffusion at high temperature and then cooled to room temperature. During this process, coralyne was not only used as a chemotherapy drug, but also resulted in the combination of poly(A) as a pH responsive molecule-gated switch blocked the pores. Under the low-pH or high-temperature condition, the hydrogen binding force declines, leading to damage of the binding structure and open-gate state. ICG, as another guest molecule, shows high-efficiency for conversion of NIR light into heat, which could promote pore opening upon NIR irradiation. The experiment results indicated the pH and NIR responsive controlled release system showed higher release efficiency than the single-mode response. Meanwhile, the photothermal effect, produced by the NIR light, not only promoted drug controlled release, but also could be used for the photothermal therapy and lead to the synergistic effect with chemotherapy.