Developing multifunctional phototheranostics with nanoplatforms offers promising potential for effective eradication of malignant solid tumors. In this study, we develop a multifunctional phototheranostic by combining photothermal therapy (PTT) and photoacoustic therapy (PAT) based on a tumor-targeting nanoagent (DBCO-ZnPc-LP). The nanoagent DBCO-ZnPc-LP was facilely prepared by self-assembling of a single lipophilic near-infrared (NIR) dye zinc(II)-phthalocyanine (ZnPc) with a lipid-poly(ethylene glycol) (LP) and following modified further with dibenzyl cyclootyne (DBCO) for introducing the two-step chemical tumor-targeting strategy based on metabolic glycoengineering and click chemistry. The as-prepared DBCO-ZnPc-LP could not only convert NIR light into heat for effective thermal ablation but also induce a thermal-enhanced ultrasound shockwave boost to trigger substantially localized mechanical damage, achieving synergistic antitumor effect both in vitro and in vivo. Moreover, DBCO-ZnPc-LP can be efficiently delivered into tumor cells and solid tumors after being injected intravenously via the two-step tumor-targeting strategy. By integrating the targeting strategy, photoacoustic imaging, and the synergistic interaction between PTT and PAT, a solid tumor could be accurately positioned and thoroughly eradicated in vivo. Therefore, this multifunctional phototheranostic is believed to play an important role in future oncotherapy by the enhanced synergistic effect of PTT and PAT under the guidance of photoacoustic imaging.

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A theranostic nanozyme (Au NCs-ICG) decomposes intratumoral H2O2 to O2, subsequently enhancing photodynamic therapy and radiotherapy with the guidance of multimodal imaging.

Detection and visualization of hydrogen sulphide (H2S) is crucial for understanding its physiological and pathological roles towards human health and diseases, but precisely tracking of H2S in vivo remains challenging due to the limitations of available analytical methods. In this study, we developed a novel ratiometric photoacoustic (PA) nanoprobe for selective detection and imaging of H2S in biological fluids, live cells, brain tissues and animals. The nanoprobe AzHD-LP was fabricated by encapsulation of a newly synthesized H2S-responsive near-infrared (NIR) dye (AzHD) within a liposome (LP). The as-prepared AzHD-LP exhibits a dramatically red-shift response of its absorption peak after reduction reaction of AzHD with H2S: the absorbance of AzHD-LP centered at 600 and 700 nm is decreased and increased, respectively, producing a turn-on ratiometric PA signal in the presence of H2S. Typically, under the excitation of a 532 nm and 700 nm pulsed laser, the selective detection and imaging of H2S was achieved in aqueous solution, living cells and brain tissues of Alzheimer's diseased mice. Moreover, after AzHD-LP conjugated with a tumor-targeting peptide - c(RGDyK) as RGD-AzHD-LP - ratiometric PA mapping of the intratumoral generated H2S in the HCT116 colon tumor-bearing live mice was demonstrated.