Fabrication Of Responsive Tumor Imaging-guided Therapy Platform Based On Nanoparticles With Special Morphology

Tumor theragnostic has always been a hot spot in the field of biomedicine.The battle with disease,however,is still difficult and with pronounced side effects.It is possible to construct responsive diagnosis and treatment platforms from endogenous or exogenous stimuli to control the therapy and minimize adverse effect of normal region based on the characteristics of the tumor microenvironment and physicochemical properties of materials.The study of the organic/inorganic nanohybrids platform has promoted the development of stimuli-responsive systems.Nanoparticles with suitable morphology can have better properties which are beneficial to their biological applications.We prepared one-dimensional Calcium carbonate-methylene blue(CaCO3-MB)nanohybrids to construct an endogenous responsive system and explored the therapeutic effect and imaging functions of the nanocomposite.Then a series of carbon-based nanoparticles with different morphologies were formed as the matrix to investigate the effect of the morphology on the gene therapy after assembly with the cationic polymer.After the drug was loaded,the corresponding multi-functional imaging-guided system for exogenous(near-infrared light,NIR)stimulation was prepared.The main work is summarized as follows:1.Utilizing the advantages of high endocytosis efficiency of one-dimensional nanoparticles.Poly(acrylic acid)(PAA)was utilized to stabilize CaCO3-MB nanorods with aspect ratio of 4 which formed by co-precipitation reaction of Ca2+,CO32-and photosensitizer MB.The experimental results show that reactive oxygen species(ROS)can be effectively produced in solution under specific light power and illumination time,and it has desirable therapeutic effectiveness against cancer cells.And at a lower pH which mimicked tumor microenvironment,MB can be released,and CO2 is produced to achieve ultrasound imaging-guided photodynamic therapy at the same time.It is an endogenous responsive diagnosis and treatment platform with simple synthesis and excellent therapeutic effectiveness.2.Hollow carbon nanoparticles with different morphologies were controllable prepared.After assembly with cationic polymer poly(glycidyl methacrylate)(PGEA),gene carriers with different morphologies were constructed.The carbon nanoparticles with superior morphology were obtained by gene transfection efficiency.The best morphological organic/inorganic nanohybrids were loaded with drugs,and then supramolecular gatekeeper induced by NIR was constructed by the assembly of adamantanecarboxylic(Ad)and cyclodextrin(CD).The photothermal behavior of carbon nanoparticles were used to control drug release with NIR irradiation.The experimental results show that hollow carbon nanoparticles with rough surface have the highest gene transfection efficiency,and the release of hydrophobic drugs can be controlled by NIR irradiation.Finally,the combined gene therapy,photothermal therapy and NIR-activated chemotherapy guided by photoacoustic(PA)imaging can be realized.The excellent anti-tumor and PA-imaging effect were finally proved by in vitro and in vivo experiments.The multifunctional platform may provide new strategy for tumor diagnosis and treatment.