Preparation And Properties Of Nanomaterials For Theranostics

As one of the important factors threatening human health,tumors have become a research hotspot in the fields of materials,chemistry,physics,molecular biology,medicine and related interdisciplinary fields.The five-year survival rate of tumor in localized stage is far from that in distant stage.Timely diagnosis and effective treatment in localized stage of tumors can significantly improve the cure rate and increase the living standard of patients.At present,the common treatment methods for cancer have gradually changed from traditional treatment methods such as surgery,radiotherapy and chemotherapy to multi-therapy methods integrating gene therapy,immunotherapy and phototherapy.The ability to combine diagnostic and therapeutic agent to prepare theranostic materials can not only be used to detect tumors,but also to effectively monitor the location of tumors and the process of drug release.Due to the enhanced permeability and retention effect of solid tumors,nanomaterials can be passively targeted and enriched in solid tumors.Functionalized nano-diagnostic integrated materials can pass through the microenvironment or tumor cells after material enrichment.The response of the internal environment releases the therapeutic drug,which reduces the side effects on other cells while treating.This thesis focuses on the diagnosis agents and therapeutic drugs.Based on the controllable design of functionalized nanomaterials,a variety of new nano-integrated intelligent materials have been prepared to explore the diagnosis and treatment of tumors.New methods are provided for the diagnosis and treatment of tumors.The main research contents and results are as follows:1.Fe₃O₄ with a particle size of about 10 nm was prepared by oil phase pyrolysis method.The phase-transfer method was used to convert oil-soluble iron oxide into water phase by PESA to form a nano-bowl,which was then coated with polydopamine.The surface modification has prepared a nano-diagnostic system that combines MRI diagnosis with chemotherapeutic drug delivery and sustained release under acidic conditions.The nanoclusters are in the shape of a bowl with a negative charge on the surface and a particle size of about 130 nm.At the same time,the nanoclusters retain good T2 MRI capability,and the r2 relaxation rate is 161.4 s^-1·m M^-1,which could load water-soluble chemotherapeutic drugs like doxorubicin hydrochloride and irinotecan hydrochloride.The drug-loading rates were 241μg/1 mg Fe₃O₄,203μg/1 mg Fe₃O₄,respectively.Those drugs could be slowly released under acidic conditions,the cumulative release rates under acidic conditions for 18 hours reached 44%and 12%,respectively.2.A water-soluble irinotecan-loaded Fe₃O₄@CPT nanocluster was prepared by a one-step solvent evaporation method using oil-soluble Fe₃O₄ and a synthesized irinotecan prodrug.The particle diameter of Fe₃O₄@CPT was about 117 nm,has good monodispersity（PDI=0.169）with a strong positive charge on the surface.It shows good stability in aqueous solution,culture solution and fetal bovine serum.The mass ratio of irinotecan/iron oxide in the system is as high as 15.9.The and the irinotecan drug can be slowly released under the acidic condition of p H=5.0,while retaining the ability of iron oxide to shorten the transverse relaxation time of water molecules,r2relaxation rate is 189 s^-1·m M^-1.Besides of that,Fe₃O₄@CPT could be uptake by cells through lysosomes,the surface of the positive charge and the nature of the nanomaterials greatly increase the uptake of cells,cells The intake is 2-3 orders of magnitude higher than irinotecan hydrochloride.This nanoformular also have good MR imaging effects in vivo and in vitro,which demonstrats that Fe₃O₄@CPT is a kind of MRI guided drug-release nanotheranostic system.3.Upconversion nanoparticle NaYF₄:Yb³⁺,Er³⁺was prepared through solvothermal method with sodium oleate as the sodium source.The size was about 7-8nm.Then,an inert shell of NaYF₄ was coated by hot-injection method,making NaYF₄:Yb³⁺,Er³⁺@NaYF₄ core-shell upconversion nanoparticles（UCNPs）.The addition of the inert shell can effectively reduce the surface defects of the Upconversion nanoparticle NaYF₄:Yb³⁺,Er³⁺and then significantly enhance the fluorescence property.The size of this core-shell upconversion nanoparticle is about 13 nm.The surface modification of UCNPs was performed by using protoporphyrin（PPIX）,which is a photosensitizer.The UCNPs could then self-assemble into water soluble nano-clusters（UCNPs@PPIX）with the size about 100 nm.The nanoclusters can use near-infrared light at 980 nm as an excitation source to excite the ability of PPIX photodynamic therapy through fluorescence resonance energy transfer.4.Prodrug compound TCPP（SN-38）₄ was prepared by linking the photosensitizer meso-tetrakis（4-carboxyphenyl）porphyrin（TCPP）with the chemotherapeutic drug 7-ethyl-10-hydroxy-camptothecin（SN-38）through ester bond.At the same time,a water-soluble PS nanosheet（PS-14 NSs）was prepared by re-precipitation method.PS-14 NSs have a size of about 113 nm with good monodispersity（PDI=0.138）.The nanosystem,with a molar ratio of SN-38/TCPP of 1:4,does not contain any additional carrier,which means it is composed of 100%cancer-treated active compound.PS-14 NSs can increase cell uptake due to its strong hydrophobicity.The IC50 of PS-14 NSs on HT-29 cells is about 37 n M,which is a certain improvement compared with SN-38.PS-14NSs could form a FRET system with SN-38 as donor and TCPP as acceptor.It can be observed that it can slowly release TCPP and SN-38 under the acidic condition of p H=5.0 by the change of fluorescence intensity.The TCPP component in PS-14 NSs allows it to have certain cell imaging capabilities,and the lysosomes of cells can be clearly seen in the red.In addition,the photodynamic therapy ability of TCPP has also been preserved.PS-14 NSs could generate singlet oxygen to kill tumor cells under red LED light.Besides of that,it can promote the break of ester bond and induce the release of SN-38 with light irradiation.This is a nanotheranostic system that combines the chemotherapy,photodynamic therapy,and fluorescence imaging.