Preparation Of Drug-loaded Copper Sulfide Nanocages For Cancer Diagnosis And Treatment

Nowadays,cancer has become as one of the lethal diseases,which seriously threatens human health.Surgery,chemotherapy and radiotherapy are the primary methods for cancer treatment in clinics.However,these three standard therapies have their intrinsic defects: surgery is risky in causing trauma and complications;unitary chemotherapy or radiotherapy may lead to toxicity and side effects toward normal tissues and organs because of the weak targeting.In recent years,nanomedicine,as an emerging research field,has shown great potential in cancer theranostics thanks to its unique features of small size effect and surface effect.Compared to traditional medicines,nanomedicine advances in many aspects,including specific drug targeting,controlled drug release,good biocompatibility and versatile functionalization,which favors on-target and on-demand tumor therapy.However,in real clinical treatment,single mode usually fails to achieve superior therapeutic effect,and thus the development of nanosystems for multimodal therapy(e.g.,chemotherapy,photothermal therapy,photodynamic therapy,etc.)has become a “hot” research topic in drug design and development.In this thesis,a novel nanoplatform with drug was constructed encapsulation based on hollow mesoporous copper sulfide nanoparticles.The hollow mesoporous copper sulfide nanoparticles were loaded with chemotheupic drug of doxorubicin(DOX)and pHotosensitizer of chlorin e6(Ce6).Meanwhile,the copper sulfide(CuS)nanoparticles exhibited good photothermal properties and biocompatibility.Herein,we designed and prepared a series of CuS-basednanoplatforms with drug loading for tumor theranosics.This thesis is mainly composed of two sections:Firstly,CuS nanocarriers with hollow mesoporous structure were synthesized through a hydrazine hydrate reduction method and ion exchange method.Then,PEG was conjugated onto the surface of CuS nanocarriers to enhance the biocompatibility and blood circulation of the nanocomposites.Subsequently,DOX and Ce6,a photosensitizer,were simultaneously loaded into the cavity of CuS nanocore by physical adsorption.The successful synthesis of the nanocomposites was confirmed by transmission electron microscopy(TEM),ultraviolet spectrophotometer,X-ray powder diffraction(XRD),X-ray photoelectron spectroscopy(XPS).Then,human breast cancer cell line(MCF-7)and mouse breast cancer cell line(4T1)were selected to evaluate the tumor cell killing effect mediated by the nanocomposites in vitro.The results showed that the nanocomposites could significantly inhibit the proliferation of tumor cells and induce cell apoptosis.In addition,pharmacokinetics of as-synthesized nanocomposites were analyzed by quantify the content of [Cu] using coupled plasma emission spectrometry(ICP-OES).The results showed that the nanocomposites with PEG modification could effectively prolong the blood circulation time in vivo.Meanwhile,the anti-tumor effect in vivo was verified by establishing 4T1 tumor model on mice.The nanocomposite group exhibited the most significant tumor suppression effect,demonstating a superior anti-tumor effect toward breast carcinoma..To realize controlled drug release,on the basis of hollow copper sulfide loaded with DOX and Ce6,thermosensitive phase change material(PCM)was encapsulatedin the surface nanopores of the nanocomposites.The underlying mechanism is that the melting point of the phase change material is 38.5 ?,and it will not dissolve at room temperature(25 ?)or physiological temperature(37 ?).However,when being irradiated by near infrared light,the hollow copper sulfide nanocarriers converts light energy into heat energy.When the temperature rose above 38.5 ?,the phase change material began to dissolve,resulting in the exposure of the tiny holes on the surface of nanocomposites.The nanoparticles can simultaneously realize the combination of photothermal therapy,photodynamic therapy and chemotherapy,as well as photothermal imaging and fluorescence imaging and other tumor diagnosis and treatment methods.In vitro cell experiments exhibited that the nanodrug can effective inhibit the growth of tumor cells.The anti-tumor effect was futher evaluated using BALB/c mice bearing 4T1 tumors in vivo.Compared to the control groups,as-synthesize nanocomposites exhibited an outstanding tumor eradication outcome.