Synthesis,Properties And Biomedical Applications Of Copper Chalcogenide Photothermal Agents

As a minimally invasive and potentially effective treatment alternative to conventional approaches,photothermal ablation therapy(PTA)has attracted much interest.In particular,near-infrared(NIR,λ = 700-1100 nm)laser-induced PTA has been paid increasing attention,because the NIR laser is absorbed less by biological tissues and the typical penetration depth of the NIR(such as 980 nm)light can reach several centimeters in biological tissues.When applying the NIR laser to treat cancer tissues,photothermal agents which can convert the NIR light energy into thermal energy are generally indispensable.Thus,for promoting the photothermal conversion efficiency and particularly improving lasers’ discrimination for the PTA of the targeted cancers,it is very important to develop photothermal agents with low cost and high photothermal conversion efficiency.In this study,we developed several kinds of low cost,high photothermal conversion efficiency copper chalcogenide photothermal agents and copper chalcogenide based multifunctional photothermal agents.1)flower-like CuS superstructures as an efficient 980 nm laser-driven photothermal agentTo address the unsatisfied photothermal conversion efficiency limitations of the copper chalcogenide,we developed a novel flower-like CuS superstructure photothermal agent with higher NIR photothermal conversion efficiency.These flower-like CuS superstructures were synthesized by using a controllable hydrothermal route assisted with poly(vinyl pyrrolidone)at 180 °C for 48 h.Since CuS superstructures are comprised of the faceted end planes of well-shaped crystals which can serve as good laser-cavity mirrors to enhance the photoabsorption,the absorption intensity of the as-synthesized CuS superstructures is as almost 2 times as that of the comparable CuS hexagonal nanoplates in the whole wavelength region,especially in the NIR region.Compared with the previous results,CuS superstructures afford higher photothermal conversion efficiency at much lower laser irradiation power.For example,aqueous dispersion containing CuS superstructures(0.07 mg/mL)exhibits a temperature increase of 11 °C under the irradiation of 980 nm laser with very low output power(～0.51 W/cm2)which is safe enough to human skin.Whereas,aqueous dispersion made of 3 nm CuS nanoparticles(0.07 mg/mL)only exhibits a temperature increase of 12.7 °C under the irradiation of 808 nm laser with high output power(24 W/cm2)over a period of 5 min in the previous results.Furthermore,if the aqueous dispersion is covered with a layer of chicken skin(thickness:-1 mm)as a model of biological tissues,its temperature can still be increased by 10.7 0C in 5 min,because 980 nm light penetrates deeper into biological tissues than visible light.More importantly,cancer cells packaged by chicken skin or in vivo can be efficiently killed by the photothermal effects of CuS superstructures under the irradiation of 980 nm laser with conservative and safe power density of 0.51 W/cm2 over a short period(5-10 min).These results demonstrate the promising application of the CuS superstructures in the PTA of in vivo tumor tissues.2)vacancy-doped copper chalcogenide photothermal agent with small diameter and high heat conversion efficiencyRecently,Alivisatos et al.demonstrated that the Cu2-xS nanocrystals with vacancy concentrations of-1021 cm-3 show obvious localized surface plasmon resonances(SPR)absorption characteristics similar to those of metals.Unlike metals,plasmon resonance frequencies of doped semiconductors can be modified by changing the material’s composition,creating new opportunities for plasmonic manipulation of light.Based on this theory,we developed two kinds of hydrophilic vacancy-doped copper chalcogenide,Cu2ZnSnS4 nanoparticle and Cu9S5 plate-like nanocrystals which are prepared by a simple solvothermal method and combing a simple modified thermal decomposition(from a single molecular precursor)and ligand exchange route respectively.The morphology,composition,structure,surface and absorption properties of the two kinds of vacancy-doped copper chalcogenide have been characterized carefully by TEM,SEM,XRD,FT-IR and UV-VIS-NIR techniques.The TEM results show that the two kinds of copper chalcogenide have small diameter(<100 nm),and the UV-VIS-NIR spectrum of them demonstrate that the absorption intensity of Cu9S5 plate-like nanocrystals is much higher than that of the Cu2ZnSnS4 nanoparticles in the whole wavelength region,especially in the NIR region.Hence,the Cu9S5 plate-like nanocrystal was used as one excellent example to investigate the photothermal conversion ability of the vacancy-doped copper chalcogenide.Compared with the Au nanorod which has been widely investigated,the aqueous dispersion of as-synthesized Cu9S5 plate-like nanocrystals shows higher extinction coefficient(～1.2×109 M-1cm-1)at 980 nm,which should be attributed to strong localized surface plasmon resonances(SPR)arising from p-type carriers.The exposure of the aqueous dispersion of Cu9S5 nanoplates(40 ppm)to 980 nm laser with a power density of 0.51 W/cm2 can elevate its temperature by 15.1°C in 7 min;a 980 nm laser heat conversion efficiency reaches as high as 25.7%,which is higher than that of the as-synthesized Au nanorods(23.7%from 980 nm laser)and the recently reported Cu2-xSe nanocrystals(22%from 808 nm laser).Importantly,cancer cells in vivo can be efficiently killed by the photothermal effects,which are realized by a very low concentration(40 ppm)aqueous dispersion of the Cu9S5 nanoplates under the irradiation of 980 nm laser with a low and safe power density of 0.51 W/cm2.Therefore,these Cu9S5 nanoplates have a great superiority as a new photothermal agent for the NIR induced PTA of cancer,due to their small size(<100 nm)and high photothermal conversion efficiency,as well as their low cost and low cytotoxicity.3)ultrasmall multifunctional Fe3O4@Cu9S8 core-shell nanostructures photothermal agentMultifunctional nanostructures displaying magnetization and near-infrared(NIR λ =700-1100 nm)absorption have been the subject of considerable attention,because of their dual-mode capabilities.Copper chalcogenide semiconductors have been a new kind of promising photothermal agent due to their low cost and high photothermal conversion efficiency.In addition,iron oxide has been used as a commercialized T2-weight magnetic resonance(MR)imaging contrast agent due to its excellent magnetic property.In this context,the integration of copper chalcogenide semiconductor with superparamagnetic iron oxide to form uniform ultrasmall core-shell composite particles has potential for simultaneous bioimaging and photothermal therapy.Herein,we designed the synthesis of a serials of ultrasmall(<10 nm),monodisperse,and precisely size controllable core-shell MFe2O4(M=Fe,Ni,Co)@Cu9S8 nanostructures(NSs).As a typical example,Fe3O4@Cu9S8(IOCS)was used to investigate their magnetic and NIR absorption properties.The hysteresis loops of IOCS core-shell NSs exhibit no remanence or coercivity at room temperature,suggesting that the superparamagnetic characteristics of the IOCS core-shell NSs.In addition,the saturated mass magnetization still shows 34.1 emu/g,even though it has the weight contribution from the nonmagnetic Cu9S8 material.Importantly,the IOCS core-shell NSs also show an increased absorption with the increase of wavelength in the NIR region and broad absorbance peak centered at 960 nm,which is attributed to the absorption of the Cu9S8 material due to the localized surface plasmon resonances(SPR)arising from p-type carriers in vacancy-doped semiconductor.To obtain hydrophilic IOCS core-shell NSs for the biological applications,amphiphilic polymer(oleylamine modified hydrolyzed polymaleic anhydride)was used to modify the surface property of the IOCS core-shell NSs.The higher r2 relaxivities(141.4 mM-1s-1)and r2/r,ratios(67),which are advantageous for 2-weighted MR imaging,and 16.02%photothermal conversion efficiency of the hydrophilic IOCS core-shell NSs suggest that it can be used as both a T2-weight contrast agent which generates dark contrast in MR images and a photothermal agent which can convert the light energy into thermal energy.The evidence of the enhanced contrast in the mouse after being injected with the IOCS core-shell NSs’ solution and the IRT imaging results which show obvious contrast before and after irradiation of the 980 nm laser further demonstrate the applicability of IOCS core-shell NSs for the MR imaging and IRT imaging.All cancer cells can be killed by the IOCS core-shell NSs when exposed to the irradiation of 980 nm laser,while treatment with the 980 nm laser irradiation or the IOCS core-shell NSs alone has no obvious effect on the cancer cells.These results imply that the IOCS core-shell NSs are a promising candidate as a photothermal agent for the PTA of cancer cells.Thus,the ultrasmall multifunctional IOCS core-shell NSs have a great potential for MR and IRT imaging-guided photothermal tumor therapy.Such an ultrasmall,low cost and highly efficient theranostic agent would remarkably improve the methodologies for cancer diagnosis and therapy.