Multimodal Imaging And Anti-Tumor Properties Of Several Gold/Rare Earth Based Upconversion Luminescence Core-Shell Nanomaterials

A multifunctional core-shell nanocomposite based on noble metal plasmons combined with upconversion material has emerged as a promising cancer theranostics nanoplatform that integrates properties such as multimodal imaging,photothermal effects,good biocompatibility,and efficient therapy.However,a reasonable combination of plasmons and upconversion materials,as well as increased penetration depth,has always challenged the anti-cancer efficiency.Besides,as the temperature is fatal for photothermal therapy(PTT),enhancing photothermal conversion efficiency is essential for improving PTT efficacy.In PTT,simultaneous achievement of imaging and hyperthermia mediated by a single laser inevitably encounters the risk of damaging normal tissues before treatment.For precise targeting therapy,nanocarriers are typically employed to realize tumor-guided delivery of chemotherapeutic drugs,which should ideally kill cancer cell without side effect under controlled release.The main research content is list as below.Firstly,we developed a novel type of thermalfluorescent core-shell hybrid nanocomposite incorporating rare-earth Yb3+ and Er3+ ion doped GdOF as the shell and gold nanorods(GNRs)as the core,creating upconversion nanorods(UCNRs)of GNRs@GdOF:Yb3+,Er3+.In order to facilitate the absorption or excretion of UCNRs in vivo,we designed gold nanorods with lower aspect ratios by reducing the amount of cetyltrimethylammonium bromide(CTAB)in the growth solution.More importantly,under 980 nm near-infrared(NIR)light irradiation,the green and red emissions of GdOF:Yb3+,Er3+generally overlap with the visible absorbance of GNRs;by altering the contents of Yb3+and Er3+ions appropriately,the localized surface plasmon resonance(LSPR)absorption of low aspect ratio GNRs under 980 nm NIR laser excitation can be enhanced for improving the PTT efficiency.Furthermore,in vitro and in vivo assays reveal that the composite has excellent bio-compatibility and cancer therapy efficiency.This multi-functional nanocomposite,which possesses upconversion luminescence and photothermal and biocompatibility properties,shows strong potential for application in bio-imaging and photothermal anti-cancer therapy.Besides,a unique kind of fluorescent thermalmagnetic resonance core-shell upconversion nanostructure has been designed and fabricated to simultaneously achieve PTT and multimodal imaging.GNRs are used as the plasmon cores and NaGdF4 with rare-earth Yb3+/Er3+ ions co-doping are used as the upconversion luminescence(UCL)shells,merging into UCNRs of GNRs@NaGdF4:Yb3+,Er3+.A NaGdF4 shell synthesized by a hydrothermal method can substitute for the CTAB on the surface of GNRs,which offers the benefits of reducing toxicity and increasing biocompatibility.More significantly,the red and green emission of Yb3+/Er3+ couples convert NIR into visible light,appropriately overlapping with absorbance of GNRs,which improves the photothermal conversion efficiency.Meanwhile,we designed small and low-aspect-ratio GNR cores for the absorption of UCNRs in vivo.Verification with evidence from in vivo and in vitro assays shows that these core-shell UCNRs exhibit a talented potential application in multimodal bioimaging and PTT.Furthermore,a quasi core-shell structured GdOF:Yb/Er@(GNRs@BSA)nanohybrid was designed and fabricated by conjugating GNRs on the surfaces of GdOF:Yb/Er nanoparticles by a facile procedure.By alternating NIR light appropriately,high photothermal efficiency for PTT and good UCL imaging can be respectively achieved in this structure,which can substantially solve the heat induced risk during the theranostic process.Furthermore,good biocompatibility and phagocytosis can be realized by modifying bovine serum albumin(BSA)on the surface of GNRs,and the conjugation of folic acid(FA)endows this nanohybrid with targeting function.It is noted that the size of GNRs prepared by one-pot method is much smaller than that by seed-mediated method,which is not only conducive to make uniform heat distribution during intratumoral therapy,but also contribute to the nanohybrid metabolic decomposition and fluorescence tracer after treatment.Moreover,this product can also be utilized as good magnetic resonance imaging(MRI)and computed tomography(CT)contrast agent,which can provide versatile imaging properties in the field of cancer clinical treatment.Finally,we developed a novel anti-tumor platform by combining upconversion nanoparticles with protein-capped gold nanodots through a facile route,following by loading chemotherapeutic drug(doxorubicin,DOX)and conjugating targeting agent(folic acid,FA).Such nanoplatform with luminescence resonance energy transfer(LRET)effect showed enhanced PTT efficacy under near-infrared(NIR)laser irradiation,and FA conjugation is capable of further targeting cancer cells,namely the focus location in vivo.Meanwhile,the nanocarrier with pH-sensitive DOX release ability would contribute to intensive release responding to acidic tumor microenvironment assisted by NIR light excitation induced heat effect,further improving in vivo anti-tumor efficiency.Additionally,by combining our upconversion/Au nanohybrid with multimodal imaging,direct cancer cell killing responses could be obtained at a deeper penetration depth,promising for completely inhibiting tumor proliferation.