Investigation Of Luminescent Ceramic Fibers For Cancer Therapy And Diagnosis

Cancer is one of the greatest threats to human health.Research on novel therapeutic technologies for multi-type cancer is currently a global research hotspot.Surgical resection,chemotherapy,and radiotherapy are the three most common treatments for cancer,but due to the intrinsic defects of these three types of treatment technology,the efficiency of cancer treatment is still very low,and the patient mortality rate remains high.The local drug delivery system is a new type of cancer treatment platform.It is a method of local implantation of tumors to achieve high concentration and controlled release of therapeutic functional factors at the lesion site.Compared with traditional chemotherapy and granular drug delivery systems,such treatment platforms have the advantages of strong targeting,high drug utilization,small side effects,and good patient compliance.Electrospinning technology is a convenient and suitable method for the preparation of macro-volume-produ:ced fiber materials.The obtained one-dimensional materials have various shapes,microscopic structures and extracellular matrix structures.Therefore,based on electrospun fiber materials has broad prospects in the biomedical field.In this paper,a series of multi-functional upconverting luminescent nanofiber materials were prepared by electrospinning and combined with various cancer treatment functional factors.Application exploration of these materials were systematically developed in the areas of drug delivery,tumor treatment,and early detection of tumors.The content is as follows:(1)A variety of fine photoluminescent STO:Er nanofibers with porous structures were successfully synthesized as a new localized drug delivery system for delivering model drug via electrospinning for the first time.After the surface modification with amino groups,the drug loading capacity was remarkably increased from-35%to?50%.Meanwhile,the amino-modified nanofibers present a rather sustained drug releasing kinetics compared to unmodified nanofibers due to the chemical bonding formed between EBU molecules and amino groups.When immersed in the PBS solutions with different pH values(7.4,5.8,and 4.7),the amino-modified nanofibers present a significantly accelerated drug releasing rate with the decreased pH value.More importantly,in addition to the pH-triggered drug releasing properties achieved,the upconversion luminescence phenomenon of the amino-modified STO:Er nanofibers corresponds well with the drug releasing progress.Fast drug release behavior(in an acid environment)induces rapid PL emission enhancing effect and vice versa.The main mechanism is the quenching effect of the C-Hx groups of drug molecules with vibration frequencies from 2850 to 3000 cm-1.(2)Through the selection and regulation of surfactants of different kinds and contents in the sol-gel process,a series of electrospinning STO:Er nanofibers materials with controlled microstructural features were achieved.When three surfactants(PVP,F127 and CTAB)were combined for electrospinning precursor,STO:Er nanofibers present the highest surface area and lowest pore dimension(?10 nm).In consequence,the higher DOX loading capacity,more sustained release kinetics as well as the stronger in-vitro anticancer efficacy were achieved when using STO-M2 nanofibers comparing to other two samples.More importantly,due to the construction of fluorescence resonance energy transfer(FRET)effect between DOX molecules and STO:Er nanofibers,the intensity ratio of green to red emission,I550/I660 ratio,corresponds effectively with DOX releasing progress.STO:Er nanofibers(STO-M2)with most sustained DOX release kinetics induce the tardiest increase of I550/I660 ratio,and vice versa.Further,a linear correlation between the I550/I660 ratio and the percentage of DOX molecules released was uncovered,and this can be utilized as a standard curve for evaluating the DOX releasing kinetics in a quantitative manner.(3)PAA decorated SrTiO3:Yb,Ho nanofibers were designed and synthesized as a multifunctional LDDS via electrospinning and multiple surface modifications.The nanofibers emitted strong upconversion green fluorescence under 980 nm laser irradiation and possessed good cyto-compatibility.The decoration of PAA molecules inhibited burst release in neutral environment and improved DOX loading capacity,from 9.5%to 39%.The pH-responsive drug release was observed due to promoted protonation of PAA molecules in acidic buffer solution.Meanwhile,accelerated DOX release behavior was successfully achieved under 808 nm light irradiation,which consequently induced significantly enhanced killing effect to cancer cells.In addition to dual-triggered DOX release characteristics,the UCPL phenomenon of the nanofibers changed dramatically during DOX loading and release due to the FRET effect built between luminescent nanofibers and DOX molecules.The intensity ratio(I545/I655)can be a reliable probe,in both qualitative and quantitative fashion,for monitoring drug release kinetics and tracking the drug dosage released in the physiological environment.(4)CaTiO3:Yb,Er-Rose Bengal-AuNRs nanocomposites have been successfully fabricated for use in an implantable device designed for use with combined photodynamic and photothermal therapy.In the composite,RB and AuNRs served as the PDT and PTT agents,respectively.Since RB and AuNRs have matched absorption with the green and red emissions of UCPL CTO nanofibers respectively,a laser with continuous single wavelength can be employed to induce the PDT and PTT effects simultaneously.Using 980 nm irradiation,the nanocomposite can convert energy effectively from NIR light to induce a combination of heat and ROS generation.Moreover,the results from in vitro experiments demonstrated that this simultaneous therapeutic approach was significantly more effective than PDT alone.(5)A novel UCPL-based FRET biosensor utilizing amino-modified CaF2:Yb,H0@SiO2 nanofibers and AuNPs was developed for miRNA-195 detectionand the limit of detection was 2 nM.The sandwich structure formed as a result of co-hybridization of target miRNA via the action of oligonucleotides allowed the nanofibers and AuNPs to be brought into sufficiently close proximity to trigger a FRET effect.The intensity ratio of green to red emission,I541/I650,varied linearly with miRNA concentration,allowing the result to be utilized as a standard curve for quantitative determination target miRNA.