Photodynamic therapy (PDT) has recently emerged as an approach to enhance intratumoral accumulation of nanoparticles. However, conventional PDT is greatly limited by the inability of the excitation light to sufficiently penetrate tissue, rendering PDT ineffective in the relatively deep tumors. To address this limitation, we developed a novel PDT platform and reported for the first time the effect of deep-tissue PDT on nanoparticle uptake in tumors. This platform employed c(RGDyK)-conjugated upconversion nanoparticles (UCNPs), which facilitate active targeting of the nanoconstruct to tumor vasculature and achieve the deep-tissue photosensitizer activation by NIR light irradiation. Results indicated that our PDT system efficiently enhanced intratumoral uptake of different nanoparticles in a deep-seated tumor model. The optimal light dose for deep-tissue PDT (34 mW/cm2) was determined and the most robust permeability enhancement was achieved by administering the nanoparticles within 15 minutes following PDT treatment. Further, a two-step treatment strategy was developed and validated featuring the capability of improving the therapeutic efficacy of Doxil while simultaneously reducing its cardiotoxicity. This two-step treatment resulted in a tumor inhibition rate of 79% compared with 56% after Doxil treatment alone. These findings provide evidence in support of the clinical application of deep-tissue PDT for enhanced nano-drug delivery.

It is an emerging focus to explore controlled release drug delivery systems for simultaneous cancer imaging and therapy. Herein, we synthesized a photothermal sensitive multifunctional nano‐liposome drug delivery system, with doxorubicin wrapped in the hydropholic layer as the therapeutical agent and cypate doped in the hydrophobic layer as the diagnostic agent. A series of in vitro and in vivo characterization demonstrated the stability of synthesized liposome, as the DL% was 9 ± 1.5 and the EE% was 82.7 ± 2.1. And the liposome achieved the functions of target‐delivery, enhanced photochemical internalized drug release, and simultaneous chemotherapy and thermal therapy, indicating that this multifunctional nano‐liposome is a promising drug delivery system for tumor diagnosis and targeting therapy.

Reactive oxygen species (ROS) are largely produced under pathological situations. To understand the etiology of disease, it is urgent to develop efficacious probes for detecting ROS. Herein, a novel nanoconjugate detection system constructed from gold clusters (AuNCs) and quantum dots (QDs) for fluorescence ratiometric-sensing ROS was reported. Upon interacting with ROS, the red emission fluorescence (645 nm from QDs) in the detection system gradually decreased, while the green fluorescence (480 nm from AuNCs) changed little. The fluorescence ratio at the 2 wavelengths (I /I ) was linearly correlated with the ROS, which could be used for the real-time ratiometric detection of ROS. The developed nanoconjugates could be applied to monitor the ROS in inflammatory cells for its ability of generating abundant ROS and uptaking ability to nanoparticles. The stimulated ROS in inflammatory cells were monitored by AuNC-QD and the results were consistent with the traditional 2', 7'-dichlorofluorescin diacetate method, confirming the reliability of the developed method. Featured with the merits of higher photostability, low background, high accuracy of ratiometric detection, the AuNC-QD conjugate demonstrated its potential to be the probe for real-time ROS detection in inflammatory cells.

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