An Activatable Near-Infrared Molecular Chemiluminescence Probe for Visualization of NQO1 Activity In Vivo

Chemiluminescence(CL)is a promising tool for diagnostics and sensing due to its inherent excitation light-free.However,most CL probes emit exclusively visible light with limited penetration depth,hindering their broad application for in vivo deep tissue imaging.This work reports an activated unimolecular CL probe(CL-P)that emits light in the near-infrared(NIR)region allowing a superior real-time visualization and detection of NAD(P)H quinone oxidoreductase 1(NQO1)in vivo.The NQO1-specific trimethyl-locked quinone is a lock for masking the NQO1 trigger site,and it was conjugated on the NIR Schaap's dioxetane chemiluminophore,achieving not only a subtle signal-to-noise ratio even at a depth of 15 mm in the chicken breast tissues,but also sensitively detecting the positive expression of NQO1 in A549 cells.CL-P has been successfully used for visualizing the aberrantly expressed NQO1 in subcutaneous xenograft A549 tumors.To our knowledge,this is the first work reporting the detection of NQO1 activity in the NIR region by unimolecular CL mode.Overall,the NQO1-activated visualization platform provides a guideline to transform a unimolecular CL sensor into a licensed imaging agent for the in vivo detection of enzyme-related diseases.

Activatable nanoscale metal-organic framework for ratiometric photoacoustic imaging of hydrogen sulfide and orthotopic colorectal cancer in vivo

Nanoscale metal-organic frameworks(nano MOFs)have emerged as a promising biomedical nanoplatform because of their unique properties.However,the exploration of nano MOFs in photoacoustic(PA)imaging is still limited.Here,a novel hydrogen sulfide(H2 S)-activated nano copper-based MOF(Cu-MOF)was developed as a near-infrared(NIR)ratiometric PA probe for in vivo monitoring of endogenous H2 S level and orthotopic colorectal cancer imaging via in situ reaction of nano Cu-MOFs with endogenous H2 S that is closely associated with tumor growth and proliferation in colon cancer.The synthesized nano Cu-MOFs displayed excellent PA responsiveness towards tumor H2 S level with high selectivity and rapid kinetics.The result suggests the developed probe may provide a unique opportunity to investigate the malignant behaviors of H2 S-associated events in vivo.

Dual activated NIR-Ⅱ fluorescence and photoacoustic imaging-guided cancer chemo-radiotherapy using hybrid plasmonic-fluorescent assemblies

Multimodal imaging in the second near-infrared window(NIR-II)guided cancer therapy is a highly precise and efficient cancer theranostic strategy.However,it is still a challenge to develop activated NIR-II optical imaging and therapy agents.In this study,we develop a pH-responsive hybrid plasmonic-fluorescent vesicle by self-assembly of amphiphilic plasmonic nanogapped gold nanorod(AuNNR)and fluorescent down-conversion nanoparticles(DCNP)(AuNNR-DCNP Ve),showing remarkable and activated NIR-II fluorescence(FL)/NIR-II photoacoustic(PA)imaging performances.The hybrid vesicle also exhibited superior loading capacity of doxorubicin as a superior drug carrier and efficient radiosensitizer for X-ray-induced radiotherapy.Interestingly,the accumulated hybrid AuNNR-DCNP Ve in the tumor resulted in a recovery of NIR-II FL imaging signal and a variation in NIR-II PA imaging signal.Dual activated NIR-II PA and FL imaging of the hybrid vesicle could trace drug release and precisely guided cancer radiotherapy to ultimately reduce the side effects to healthy tissue.

Ultrasound-propelled Janus Au NR-mSiO_(2) nanomotor for NIR-II photoacoustic imaging guided sonodynamic-gas therapy of large tumors

Varieties of contrast agents have been developed for photoacoustic(PA)and ultrasound(US)imaging of cancers in vivo.However,access of traditional contrast agents into the sites of tumors has been principally through passive infiltration without any external force,preventing their deep penetration into the tissues of the tumors,and hindering the use of PA and US for deep tumor imaging.The concept of micro/nanomotors has been the focus of increasing attention as active theranostic agents due to their active movement in particular fluids,thereby conducting assigned tasks.Herein,US-propelled Janus mesoporous SiO_(2)partially coated gold nanorods(Au NR-mSiO_(2))were fabricated for deep tumor NIR-II PA imaging and synergistic sonodynamic-gas therapy.Following US irradiation,2,2-azobis[2-(2-imidazolin-2-yl)propane]dihydrochloride(AIPH)loaded in mSiO_(2)(Au NR-mSiO_(2)/AIPH)generated N_(2)microbubbles with high efficiency to achieve nanomotor drive.Due to the deep penetration of US,the nanomotors exhibited a capability to travel deep within sites of tumors,providing enhanced PA/US imaging inside the tumors.Furthermore,the nanomotor based cancer therapy was demonstrated through synergistic N_(2)gas and sonodynamic therapy.The US-propelled nanomotors demonstrated a novel strategy for the simultaneous PA/US dual imaging deep within tumor tissues and precise therapy of large tumors.

Mesoporous radiosensitized nanoprobe for enhanced NIR-Ⅱ photoacoustic imaging-guided accurate radio-chemotherapy

Oxygen deficiency is a major obstacle to hypoxic-related cancer theranostics,and developing the oxygen production nanoplatforms received the widespread attention.However,it is remaining a challenge to structure a nanoplatform with hypoxia alleviation effect and imaging-guided cancer radiotherapy.Herein,we present a novel theranostics nanoplatform(Au NPs/UCNPs/WO_(3)@C)comprising of tungsten trioxide(WO3)that loaded gold nanoparticles(Au NPs)and up-conversion nanoparticles(UCNPs)for improved photoacoustic(PA)imaging performance in the second near infrared window(NIR-Ⅱ,900-1,700 nm).Au NPs/UCNPs/WO_(3)@C exhibited superior oxygen-generation effect and doxorubicin loading capacity,thus serving as an efficient radiosensitizer for radio-chemo anti-cancer therapy.Importantly,the accumulated Au NPs/UCNPs/WO_(3)@C in the tumor region led to the increased NIR-Ⅱ PA imaging signal and the blood oxygen saturation signal,which could enhance radiation sensitivity and accurately guiding cancer radiotherapy to reduce side effects on normal tissues.This study with proof-of-concept confirmed the multifaceted characteristics and encouraging potential of biomimetic Au NPs/UCNPs/WO_(3)@C for NIR-Ⅱ PA imaging-guided tumor therapeutics.