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Image‐guided photodynamic therapy (PDT) has received growing attention due to its non‐invasiveness and precise controllability. However, the PDT efficiency of most photosensitizers are decreased in living system due to the aggregation‐caused singlet oxygen (1O2) generation decreasing. Herein, we present an Iridium (III) pyridylpyrrole complex (Ir‐1) featuring of aggregation‐induced emission (AIE) and 1O2 generation characteristics for image‐guided PDT of cancer. Ir‐1 aqueous solution exhibits bright red phosphorescence peaked at 630 nm, large Stokes shift of 227 nm, and good 1O2 generation ability. The 1O2 generating rate of Ir‐1 in EtOH/water mixture solution is 2.3 times higher than that of Rose Bengal. In vitro experimental results revealed that Ir‐1 has better biocompatibility and higher phototoxicity compared with clinically used photosensitizers (Rose Bengal and Ce6), suggesting that Ir‐1 can serve as a photosensitizer for image‐guided PDT of cancer. [ABSTRACT FROM AUTHOR]

• The state-of-the-art strategies to improve the 1O 2 quantum yield are summarized. • The advantages and disadvantages of these strategies are highlighted and compared. • The challenges and obstacles encountered in clinical PDT are discussed. Singlet oxygen (1O 2) generation is an essential function of photosensitizer (PS) as applied to photodynamic therapy (PDT) of cancer. As illustrated in the Jablonski diagram, the generation of 1O 2 is directly related to the process of intersystem crossing (ISC), in which a high ISC efficiency typically correlates with a high quantum yield (QY) of 1O 2. In recent years, multiple strategies have been adopted to improve ISC efficiency, including tuning chemical structures and reducing aggregation-caused quenching (ACQ), thus increase the 1O 2 QY of PS. Here, we systematically summarize and compare the advantages and disadvantages of these strategies through analysis of some representative examples. In addition, we also discuss the challenges and obstacles encountered in the development of PS with high 1O 2 generation efficiency and propose directions for future clinical applications of PDT. [ABSTRACT FROM AUTHOR]

Sonodynamic therapy (SDT) has emerged as a promising minimally invasive and selective approach for the treatment of deep tumors. In this review, SDT-associated mechanisms include reactive oxygen species (ROS) and shear force. Organic sonosensitizers was systematically classify into porphyrins, phthalocyanines, xanthenes, indocyanines, natural products, and quinolones etc. The combination of SDT with phototherapy, chemodynamical therapy, chemotherapy, starvation therapy, gas therapy and immunotherapy, improves its therapeutic efficiency. [Display omitted] • The mechanisms of SDT are discussed. • The advantages and limitations of organic sonosensitizers for SDT are reviewed. • Strategies to improve the SDT efficacy are provided. • Guidelines are offered for the design of effective sonosensitizers. Sonodynamic therapy (SDT), which involves a combination of low-intensity ultrasound (US) and a chemical sonosensitizer, has emerged as a promising minimally invasive and selective approach for the treatment of deep tumors. US not only increases cell membrane permeability, thereby enhancing the cellular uptake efficiency of chemical sonosensitizers, but also excites chemical sonosensitizers in deep tissues to generate reactive oxygen species (ROS), which in turn kill cancer cells. As compared with inorganic materials, organic sonosensitizers exhibit a defined chemical structure, controlled synthesis process, excellent biodegradability, and high ROS generation. However, they frequently exhibit poor water solubility, strong phototoxicity, and low tumor tissue targeting capacity. In this review, we address the currently accepted mechanisms in SDT and the recent progresses in organic sonosensitizers, discuss the strategies to improve the water solubility, tumor targeting capacity, biocompatibility, and therapeutic effects of organic sonosensitizers. The advantages of combining SDT with other cancer treatments, including phototherapy, chemodynamic therapy, chemotherapy, starvation therapy, gas therapy, and immune therapy are also demonstrated. Finally, the existing challenges and future perspectives on clinical SDT of tumor are discussed. [ABSTRACT FROM AUTHOR]

This tutorial review summarizes the strategies for improving the efficacy of PDT in hypoxic tumor therapy. The advantages of combining PDT with other therapeutics, such as chemotherapy, chemodynamic therapy, gas therapy, immunotherapy and gene therapy, are also demonstrated. Finally, the existing challenges and future perspectives on clinical PDT for hypoxic tumors are discussed. [Display omitted] • Advanced materials and strategies for PDT to overcome hypoxia are classified. • Novel nano-systems in enhancing anti-tumor effects are summarized. • Combining PDT with other therapeutics to achieve synergetic effects are reported. • The current challenges and further opportunities are discussed. Photodynamic therapy (PDT) has been a preferred clinical technology for treating superficial tumors due to its advantages of high selectivity, non-invasiveness and negligible drug resistance. However, the hypoxic tumor microenvironment weakens the efficiency of O 2 -dependent PDT. Moreover, the PDT process consumes a large amount of O 2 and destroys the tumor blood vessels and further blocks the O 2 supply to tumor sites. Therefore, developing more advanced materials and methods for PDT of the hypoxic tumor is an essential scientific significance. This tutorial review summarizes the strategies for improving the efficacy of PDT in hypoxic tumor therapy, which is categorized into three sections: (I) enhancing O 2 concentration in the tumor; (II) disregarding hypoxia; and (III) exploiting hypoxia. The advantages of combining PDT with other therapeutics, such as chemotherapy, chemo-dynamic therapy, gas therapy, immunotherapy and gene therapy, are also demonstrated. Finally, the existing challenges and future perspectives on clinical PDT for hypoxic tumors are discussed. [ABSTRACT FROM AUTHOR]

Lysosome targetable carbon dots which can simultaneously generate 1O 2 , OH and heat under 635 nm laser irradiation were prepared, their applications in photothermal/photodynamic synergistic cancer therapy and photoacoustic/two-photon excited fluorescence imaging were demonstrated. • Carbon dots with lysosome targeting ability was prepared. • The carbon dots exhibited negligible toxicity. • The multimodality imaging of carbon dots could be applied for diagnosis. • A highly efficient photothermal-photodynamic phototherapy of cancer was performed. Phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT) holds great potential for efficient cancer therapy by inducing reactive oxygen species (ROS) or heat into tumor. Nevertheless, PDT or PTT suffers from some limitations, e.g., PTT requires long-time and high-power laser irradiation to generate enough heat, while the hypoxia microenvironment of tumor and the limit diffuse distance of ROS hamper the efficacy of oxygen-dependent PDT. Here we reported the carbon dots (CDs) which could simultaneously generate singlet oxygen (1O 2), hydroxyl radical (OH), and heat under a 635 nm laser irradiation, with a 1O 2 generation quantum yield of 5.7% and photothermal conversion efficiency of 73.5% (the highest thus far for CDs). Significantly, the CDs can selectively accumulate in lysosome, which is an ideal organelle for phototherapy because of its key role in sustaining cellular activity and stability. Moreover, the CDs present one-photon excited (OPE) and two-photon excited (TPE) fluorescence, and excellent photoacoustic (PA) imaging capability. Combining the good biocompatibility, the as-prepared CDs was served as multi-functional phototheranostic agent for synergistic PA/fluorescence imaging, and PDT/PTT. [ABSTRACT FROM AUTHOR]

An A-D-A structured AIEgen based nanoparticles was designed for long-term imaging, and effective photodynamic therapy. The small ΔE ST of 0.227 eV make BTZPP NPs possess excellent 1O 2 generation ability, and the lysosome-targeted property further assist the treatment effect of PDT. [Display omitted] • A-D-A structured AIE photosensitizer (BTZPP) with small ΔE ST was designed. • BTZPP has large Stokes shift, deep red fluorescence and high 1O 2 quantum yield. • The lysosome targeted ability make BTZPP NPs kill cancer cells more effectively. • Imaging guided PDT of cancer was demonstrated. Photosensitizers (PSs) with aggregation-induced emission (AIE) feature show promising applications in fluorescence imaging-guided photodynamic therapy (PDT) in virtue of their enhanced fluorescence and phototoxicity in aggregate state. Seeking the ideal AIE luminogens (AIEgens) with good capability of generating reactive oxygen species is still urgent. Here we rationally synthesized an acceptor-donor-acceptor (A-D-A) structured AIEgen (BTZPP) and then prepared it into nanoparticles (NPs) through a simple re-precipitation procedure. The obtained BTZPP NPs show a deep-red emission peaked at 635 nm, a large Stokes shift of 195 nm, and a high 1O 2 generation quantum yield of 72.3%. Moreover, these NPs can selectively target lysosomes in live cells and image mouse tumor with a high contrast and long-term tracking (up to 14 days) capability. The high-efficiency imaging-guided PDT against cancer cells and tumors is successfully demonstrated in vitro and in vivo. [ABSTRACT FROM AUTHOR]