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Combining phototherapy with other treatments has significantly advanced cancer therapy. Here, we designed and fabricated calcium-enriched carbon nanoparticles (Ca-CNPs) that could effectively deplete glutathione (GSH) and release calcium ions in tumors, thereby enhancing the efficacy of photodynamic therapy (PDT) and the calcium overload effect that leads to mitochondrial dysfunction. Due to the electrostatic interaction, π–π stacking interaction, multiple hydrogen bonds, and microporous structures, indocyanine green (ICG) was loaded onto the surface of Ca-CNPs with a high loading efficiency of 44.7 wt%. The obtained Ca-CNPs@ICG can effectively improve the photostability of ICG while retaining its ability to generate singlet oxygen (1O2) and undergo photothermal conversion (Ca-CNPs@ICG vs. ICG, 45.1% vs. 39.5%). In vitro and in vivo experiments demonstrated that Ca-CNPs@ICG could be used for near-infrared fluorescence imaging-guided synergistic calcium overload, photothermal therapy, and GSH depletion-enhanced PDT. This study sheds light on the improvement of 1O2 utilization efficiency and calcium overload-induced mitochondrial membrane potential imbalance in tumor cells. [ABSTRACT FROM AUTHOR]

Vascular disruption agent (combretastatin A-4 phosphate) and phototherapeutic (IEICO-4F) assembled nanoparticles (IFC NPs) were prepared for the first time. The IFC NPs have a high photo energy utilization efficiency of up to 96.1%, and could significantly inhibit tumor growth by photodynamic and photothermal therapy enhanced tumor vascular disruption. [ABSTRACT FROM AUTHOR]

Sonodynamic therapy (SDT) has emerged as a promising treatment approach of solid tumors given its deep tissue penetration, non-invasiveness, few side effects, and negligible drug resistance. Herein, we report the first polythiophene derivative-based sonosensitizer (PT2) containing a quaternary ammonium salt and dodecyl chains with better ultrasound stability than that of traditional sonosensitizers, such as Rose Bengal and chlorin e6. PT2 was encapsulated by folic acid-containing polyethylene glycol. The obtained nanoparticles (PDPF NPs) exhibited excellent biocompatibility, cancer cell-targeting capacity, and accumulated mainly in the lysosomes and plasma membranes of cells. These NPs could generate singlet oxygen and superoxide anions simultaneously under ultrasound irradiation. In vitro and in vivo experimental results demonstrated that PDPF NPs could induce cancer-cell death through apoptosis and necrosis, inhibit DNA replication, and ultimately achieve tumor depletion upon US irradiation. These findings revealed that polythiophene could serve as an efficacious sonosensitizer for enhanced US treatment of deep-seated tumors. [ABSTRACT FROM AUTHOR]

Phototherapeutic agents with near-infrared (NIR) fluorescence, strong reactive oxygen species generation and photothermal conversion capabilities are highly desirable for use in cancer therapy. Herein, a water-soluble NIR croconaine dye (TCR) with a thiophene-croconaine rigid core and two symmetric alkyl chains was designed and synthesized. TCR exhibits intense NIR absorption and fluorescence that peaked at 780 and 815 nm, respectively, with a high molar extinction coefficient of 1.19 × 105 M−1 cm−1. Moreover, TCR has a high photothermal conversion efficiency of 77% and is capable of generating hydroxyl radicals (OH˙) under 735 nm laser irradiation. Based on these outstanding properties, TCR has proven its application in NIR fluorescence imaging-guided synergistic photothermal/photodynamic therapy of cancer. [ABSTRACT FROM AUTHOR]

The blood–brain barrier (BBB) plays an irreplaceable role in protecting the central nervous system (CNS) from bloodborne pathogens. However, the BBB complicates the treatment of CNS diseases because it prevents almost all therapeutic drugs from getting into the CNS. With the growing understanding of the physiological characteristics of the BBB and the development of nanotechnology, nanomaterial-based drug delivery systems have become promising tools for delivering drugs across the BBB to the CNS. Herein, we systematically summarize the recent progress in organic-nanoparticle delivery systems for treating CNS diseases and evaluate their mechanisms in overcoming the BBB with the aim to provide a comprehensive understanding of the advantages, disadvantages, and challenges of organic nanoparticles in delivering drugs across the BBB. This review may inspire new research ideas and directions for applying nanotechnology to treat CNS diseases. [ABSTRACT FROM AUTHOR]

Nanosheet carriers loaded with drugs and phototherapeutics are used for effective cancer therapy, but the process remains challenging. Here, we prepared sulfur nanosheets (S-NSs) and then loaded tirapazamine (TPZ) and indocyanine green (ICG) with a loading efficiency of 6.3% and 94%, respectively. The obtained S-NSs-TPZ-ICG exhibits near-infrared (NIR) fluorescence, high 1O2 generation and photothermal conversion capabilities, good biocompatibility, and tumor microenvironment responsiveness. In vivo and in vitro experiments reveal that S-NSs-TPZ-ICG can be selectively decomposed under acidic and H2O2 conditions to release TPZ and ICG, and significantly inhibit tumor growth under laser irradiation without obvious toxic side effects. [ABSTRACT FROM AUTHOR]

Two-photon excitation (TPE) photodynamic therapy (PDT) has attracted great interest due to its distinctive properties, e.g., good penetration ability of biological tissues and less damage to healthy tissues. However, the conventional photosensitizers (PSs) for PDT have poor subcellular location capability and low two-photon absorption (TPA) cross section in the phototherapeutic window. Herein, we report a fascinating multi-functional TPE PS, polythiophene nanoparticles (PT NPs), for simultaneous lysosome-targetable fluorescence imaging and PDT. PT NPs show bright yellow fluorescence, good water solubility as well as excellent photo- and pH-stability. Moreover, PT NPs exhibit high singlet oxygen generation quantum yield (∼42%) and large TPA cross section (∼3420 GM). A fluorescence imaging penetration depth of 1800 μm could be reached in the tissue phantom under the TPE mode. Due to these outstanding merits and their unique clathrin- and caveola-independent intracellular uptake pathway, PT NPs have great potential for application in TPE fluorescence imaging and photodynamic therapy. [ABSTRACT FROM AUTHOR]