Deep Photoacoustic/Luminescence/Magnetic Resonance Multimodal Imaging In Living Subjects Using High Efficiency Upconversion Nanocomposites

Tumor microvessels as disease indicators are of great importance in cancer progression.Photoacoustic imaging(PAI)is particularly suitable for visualizing tumor vasculature.However,PAI usually maps a relatively small field-of-view due to moderate laser energy.At macroscopic level,fluorescence imaging can unveil tumor localization and organ distribution of in whole-body of mouse.However,fluorescence imaging often suffers from low spatial resolution and thus loses localization accuracy due to optical scattering.Although MRI is widely used in clinics and can provide an independent imaging mechanism,it requires cumbersome instrumentation and the data-acquisition is quite time-consuming.Therefore,incorporating photoacoustic(PA),fluorescence and MR multi-modal imaging is highly desired for accurate disease diagnosis and comprehensive information.Lanthanide-doped UCNPs,converting near infrared(NIR)light into visible light,possess several advantages including high tissue penetration depth,minimized auto-fluorescence background,and low toxicity in biosamples.Notably,UCNPs have been extensively explored as multi-modal imaging probes by doping various lanthanide elements.Upconversion nanoparticles(UCNPs)allow whole-body fluorescence imaging with high contrast.Unfortunately,the low quantum yield(QY)and limited optical absorption of UCNPs result in low photon-to-ultrasound conversion efficiency.Additionally,strong water absorbance at 980 nm laser leads to overheating effects.Herein,for the first time,we introduce Gd3+ doped and indocyanine green(ICG)conjugated multi-shell UCNPs at 800 nm laser excitation for upconversion luminescence(UCL),photoacoustic and magnetic resonance(MR)tri-modal imaging.Notably,the UCL intensity of multi-shell UCNPs under 800 nm excitation was significantly enhanced 10-fold greater than that of 980 nm in water.Moreover,this fluorescent nanoprobe reached a penetration depth up to 25 mm with negligible overheating effects.PAI can provide pathophysiological information by penetrating the whole tumor while maintaining submillimeter resolution.MRI,as an independent mechanism,supplied high-resolution in vivo tumor and organ imaging such as liver.The excellent tri-modal imaging capacity endows the unique nanocomposites great potential for visualizing tumor morphology,microvessel distribution,and drug perfusion at new imaging depth.