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Hollow silica spheres have been widely studied for drug delivery because of their excellent biosecurity and high porosity. However, difficulties with degradation in the tumor microenvironment (TME) and premature leaking during drug delivery limit their clinical applications. To alleviate these problems, herein, hollow organosilica spheres (HOS) were initially prepared using a "selective etching strategy" and loaded with a photothermal drug: new indocyanine green (IR820). Then, the Cu2+–tannic acid complex (Cu-TA) was deposited on the surface of the HOS, and a new nanoplatform named HOS@IR820@Cu-TA (HICT) was finally obtained. The deposition of Cu-TA can gate the pores of HOS completely to prevent the leakage of IR820 and significantly enhance the loading capacity of HOS. Once in the mildly acidic TME, the HOS and outer Cu-TA decompose quickly in response, resulting in the release of Cu2+ and IR820. The released Cu2+ can react with the endogenous glutathione (GSH) to consume it and produce Cu+, leading to the enhanced production of highly toxic ·OH through a Fenton-like reaction due to the overexpressed H2O2 in the TME. Meanwhile, the ·OH generation was remarkably enhanced by the NIR light-responsive photothermal effect of IR820. These collective properties of HICT enable it to be a smart nanomedicine for dually enhanced chemodynamic therapy through GSH depletions and NIR light-triggered photothermal effects. [ABSTRACT FROM AUTHOR]

The efficiency of photodynamic therapy (PDT) is related to the subcellular localization of photosensitizers (PSs) because organelles are associated with many fundamental life-sustaining activities. In this work, we synthesized a PS (CN) based on curcumin (CUR) and obtained enhanced PDT efficiency by simultaneously targeting lipid droplets (LDs) and the endoplasmic reticulum (ER). Compared with CUR, CN with a D–π–A–π–D structure possessed stronger intramolecular charge transfer features, resulting in longer absorption and emission wavelengths. In cell imaging experiments of CN using a confocal laser scanning microscope, a bright green emission in LDs and a weak orange emission in the ER were simultaneously observed due to its sensitivity to polarity. Surprisingly, CN with low singlet oxygen yields (0.13) exhibited an excellent photodynamic effect. Further experimental results showed that the phototoxicity of CN resulted in apoptosis by destroying the ER and ferroptosis by oxidizing polyunsaturated fatty acids (PUFAs) in LDs. This work paves the way for developing more effective photosensitizers with superior dual-targeting specificity. [ABSTRACT FROM AUTHOR]

As a class of highly dynamic organelles, lipid droplets (LDs) are involved in numerous physiological functions, and the changes in polarity of LDs are closely related to a variety of diseases. In this work, we developed two polarity-sensitive fluorescent probes (CC-CH and CC-Cl) based on curcumin analogs. CC-CH and CC-Cl with a donor–acceptor–donor (D–A–D) structure exhibited the property of intramolecular charge transfer (ICT); thus, their fluorescence emissions were significantly attenuated with increasing ambient polarity. Cell experiments indicated that CC-CH and CC-Cl showed excellent photostability, a low cytotoxicity, and a superior targeting ability regarding LDs. After treatment with oleic acid (OA) and methyl-β-cyclodextrin (M-β-CD), the polarity changes of LDs in living cells could be visualized by using CC-CH and CC-Cl. In addition, CC-CH and CC-Cl could monitor polarity changes of LDs in different pathological processes, including inflammatory responses, nutrient deprivation, and H2O2-induced oxidative stress. Therefore, CC-CH and CC-Cl are promising potential fluorescent probes for tracking intracellular LD polarity changes. [ABSTRACT FROM AUTHOR]

Two photosensitizers (CCOH and CCN) were designed and synthesized by introducing coumarin into the curcumin (CUR) structure. Compared with CUR, more reactive oxygen species (ROS) were generated by CCOH and CCN in type I and II synergy upon light irradiation. Cell experiments indicated that CCN with an excellent LD-targeting effect could be used to monitor the changes in the morphology and number of LDs in tumor cells during PDT. [ABSTRACT FROM AUTHOR]

Hydrophobic photosensitizers greatly affect cell permeability and enrichment in tumors, but they cannot be used directly for clinical applications because they always aggregate in water, preventing their circulation in the blood and accumulation in tumor cells. As a result, amphiphilic photosensitizers are highly desirable. Although nanomaterial‐based photosensitizers can solve water solubility, they have the disadvantages of complicated operation, poor reproducibility, low drug loading, and poor stability. In this work, an efficient synthesis strategy is proposed that converts small molecules into nanoparticles in 100 % aqueous solution by molecular assembly without the addition of any foreign species. Three photosensitizers with triphenylphosphine units and ethylene glycol chains of different lengths, TPP−PPh3, TPP−PPh3−2PEG and TPP−PPh3−4PEG, were synthesized to improve amphiphilicity. Of the three photosensitizers, TPP−PPh3−4PEG is the most efficient (singlet oxygen yield: 0.89) for tumor photodynamic therapy not only because of its definite constituent, but also because its amphiphilic structure allows it to self‐assemble in water. [ABSTRACT FROM AUTHOR]

Peroxalate CL as an energy source to excite photosensitizers has attracted tremendous attention in photodynamic therapy (PDT). In this work, peroxyoxalate CPPO and hypocrellin B (HB)‐based nanoparticles (CBNPs) for ultrasound (US)‐enhanced self‐exciting PDT were designed and prepared. CBNPs showed an excellent therapeutic effect against cancer cells with the assistance of US. This US‐enhanced‐chemiluminescence system avoids the dependence on external light and provides an example for inspiring more effective and precise strategies for cancer treatment. [ABSTRACT FROM AUTHOR]

Hypocrellin B (HB) derived from naturally produced hypocrellins has attracted considerable attention in photodynamic therapy (PDT) because of its excellent photosensitive properties. However, the weak absorption within a "phototherapy window" (600–900 nm) and poor water solubility of HB have limited its clinical application. In this study, two HB derivatives (i. e., HE and HF) were designed and synthesized for the first time by introducing two different substituent groups into the HB structure. The obtained derivatives showed a broad absorption band covering the near‐infrared (NIR) region, NIR emission (peaked at 805 nm), and singlet oxygen quantum yields of 0.27/0.31. HE‐PEG‐NPs were also prepared using 2‐distearoyl‐sn‐glycero‐3‐phosphoethanolamine‐N‐[methoxy(polyethyleneglycol)‐2000] (DSPE‐mPEG2000) to achieve excellent dispersion in water and further explored their practical applications. HE‐PEG‐NPs not only retained their 1O2‐generating ability, but also exhibited a photothermal conversion efficiency of 25.9%. In vitro and in vivo therapeutic results revealed that the synergetic effect of HE‐PEG‐NPs on PDT and photothermal therapy (PTT) could achieve a good performance. Therefore, HE‐PEG‐NPs could be regarded as a promising phototheranostic agent. [ABSTRACT FROM AUTHOR]

Carbon dots (CDs), a kind of phototheranostic agent with the capability of simultaneous bioimaging and phototherapy [i.e. photodynamic therapy (PDT) or photothermal therapy (PTT)], have received considerable attention because of their remarkable properties, including flexibility for surface modification, high biocompatibility, low toxicity and photo‐induced activity for malignant tumor cells. Among numerous carbon sources, it has been found that natural biomass are good candidates for the preparation of CD phototheranostic agents. In this study, pheophytin, a type of Mg‐free chlorophyll derivative and also a natural product with low toxicity, was used as a raw carbon source for the synthesis of CDs by using a microwave method. The obtained hydrophobic CDs exhibited a maximum near‐infrared (NIR) emission peak at approximately 680 nm, and high singlet oxygen (1O2) generation with a quantum yield of 0.62. The self‐assembled CDs from the as‐prepared CDs with DSPE‐mPEG2000 retained efficient 1O2 generation. The obtained carbon dot assembly was not only an efficient fluorescence (FL) imaging agent but also a smart PDT agent. Our studies indicated that the obtained hydrophilic CD assembly holds great potential as a new phototheranostic agent for cancer therapy. This work provides a new route for synthesis of CDs and proposes a readily available candidate for tumor treatment. [ABSTRACT FROM AUTHOR]

A new water-soluble fluorescent probe 1 based on hemicyanine dye is designed for selective detection of glutathione (GSH). Probe 1 shows a tremendous colorimetric and ratiometric fluorescence response toward GSH with high selectivity over cysteine/homocysteine. After nucleophilic aromatic substitution reaction with GSH, probe 1 undergoes an intramolecular aldimine condensation that leads to forming a ring, which is accompanied by 107 and 41 nm red-shifts in the absorption and fluorescence spectra, respectively. Subsequent experiments in living cells indicate that probe 1 has a good photostability and response to mitochondrial GSH level in a ratiometric manner. [ABSTRACT FROM AUTHOR]

As phototheranostic agents, carbon dots (CDs), have recently drawn considerable attention due to their excellent physicochemical properties. However, the complex synthetic route and high-cost of CDs greatly limit their practical application. To address this issue, given their nearly infinite supply from nature, Hypocrella bambusae is used as the precursor for the preparation of CDs in this study. The obtained Hypocrella bambusae CDs (HBCDs) possess good water solubility, broad absorption (350–800 nm), red-light emission (maximum peak at 610 nm), and low biotoxicity. Moreover, HBCDs can highly generate 1 O 2 (0.38) and heat (27.6%) under 635 nm laser irradiation. These excellent properties of HBCDs capacitate them to be utilized for bimodal fluorescence/photoacoustic imaging-guided synergistic photodynamic therapy (PDT)/photothermal therapy (PTT). This work provides a new candidate for tumor treatment with the combination of PDT and PTT, and explores a novel approach for the preparation of CD-based phototheranostic agents with natural biomass as raw carbon sources. [ABSTRACT FROM AUTHOR]

Two asymmetrical benzoxanthene dyes (BP-1 and BP-2) were designed and synthesized by a convenient one-step procedure from naphthaldehyde and m -aminophenol precursors. These dyes showed long-wavelength absorption, near-infrared emission (>650 nm), and large Stokes shifts (>90 nm) because of the asymmetrical introduction of the benzene ring into the xanthene structure. BP-1 exhibited high fluorescence quantum yield in organic solvents, whereas BP-2 showed very weak fluorescence due to the photoinduced electron transfer of 9-substituted groups. Cell experiments indicated that BP-1 with crescent-shape structure showed lower cytotoxicity and higher photostability than BP-2 and could rapidly stain RNA in nucleoli at low concentration. [Display omitted] • Two asymmetrical benzoxanthene dyes were synthesized by a convenient one-step procedure. • The dyes showed long-wavelength absorption, near-infrared emission and large Stokes shifts. • BP-1 could stained RNA in nucleoli rapidly with low cytotoxicity and good photostability. • BP-2 showed a very weak fluorescence and cytotoxicity due to 9-substituted groups. [ABSTRACT FROM AUTHOR]

Recently, photodynamic therapy (PDT) based on the generation of cytotoxic reactive oxygen species (ROS) has drawn great attention in tumor treatment. However, the hypoxia tumor microenvironment (TME) inhibits the generation efficacy of ROS, and the high glutathione (GSH) level in TME could neutralize the generated ROS, both of which strongly reduce the therapeutic efficiency of PDT. In this work, we first constructed the porphyrinic metal-organic framework PCN-224. Then Au nanoparticles were decorated on the PCN-224 to obtain the PCN-224@Au. The decorated Au nanoparticles could not only produce O 2 through the decomposition of H 2 O 2 in tumor sites for enhancing the generation of 1 O 2 in PDT but also deplete glutathione through the strong interactions between Au and sulfhydryl groups on glutathione to weaken the antioxidant ability of tumor cells, thus amplifying the 1 O 2 damage to cancer cells. The in vitro and in vivo experiments totally exhibited that the as-prepared PCN-224@Au nanoreactor can be used as an oxidative stress amplifier for enhanced PDT, which provides a promising candidate to conquer the limitation of intratumor hypoxia and high GSH level on PDT of cancer.

Based on coumarin and benzopyran derivatives, a dual-wavelength excitation ratiometric fluorescent probe, HABA, was prepared to detect H 2 S. The HABA probe showed good selectivity and anti-interference abilities during H 2 S detection. Fluorescence co-localization experiments showed that HABA had excellent localization abilities toward mitochondria and lysosomes. More importantly, HABA can not only detect exogenous H 2 S, but it can also detect endogenous H 2 S, indicating that HABA has high application potential and value in the biological field.

Hydrophobic photosensitizers greatly affect cell permeability and enrichment in tumors, but they cannot be used directly for clinical applications because they always aggregate in water, preventing their circulation in the blood and accumulation in tumor cells. As a result, amphiphilic photosensitizers are highly desirable. Although nanomaterial-based photosensitizers can solve water solubility, they have the disadvantages of complicated operation, poor reproducibility, low drug loading, and poor stability. In this work, an efficient synthesis strategy is proposed that converts small molecules into nanoparticles in 100 % aqueous solution by molecular assembly without the addition of any foreign species. Three photosensitizers with triphenylphosphine units and ethylene glycol chains of different lengths, TPP-PPh 3 , TPP-PPh 3 -2PEG and TPP-PPh 3 -4PEG, were synthesized to improve amphiphilicity. Of the three photosensitizers, TPP-PPh 3 -4PEG is the most efficient (singlet oxygen yield: 0.89) for tumor photodynamic therapy not only because of its definite constituent, but also because its amphiphilic structure allows it to self-assemble in water., (© 2021 Wiley-VCH GmbH.)

Peroxalate CL as an energy source to excite photosensitizers has attracted tremendous attention in photodynamic therapy (PDT). In this work, peroxyoxalate CPPO and hypocrellin B (HB)-based nanoparticles (CBNPs) for ultrasound (US)-enhanced self-exciting PDT were designed and prepared. CBNPs showed an excellent therapeutic effect against cancer cells with the assistance of US. This US-enhanced-chemiluminescence system avoids the dependence on external light and provides an example for inspiring more effective and precise strategies for cancer treatment., (© 2021 Wiley-VCH GmbH.)

Hypocrellin B (HB) derived from naturally produced hypocrellins has attracted considerable attention in photodynamic therapy (PDT) because of its excellent photosensitive properties. However, the weak absorption within a "phototherapy window" (600-900 nm) and poor water solubility of HB have limited its clinical application. In this study, two HB derivatives (i. e., HE and HF) were designed and synthesized for the first time by introducing two different substituent groups into the HB structure. The obtained derivatives showed a broad absorption band covering the near-infrared (NIR) region, NIR emission (peaked at 805 nm), and singlet oxygen quantum yields of 0.27/0.31. HE-PEG-NPs were also prepared using 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-mPEG2000) to achieve excellent dispersion in water and further explored their practical applications. HE-PEG-NPs not only retained their 1 O 2 -generating ability, but also exhibited a photothermal conversion efficiency of 25.9%. In vitro and in vivo therapeutic results revealed that the synergetic effect of HE-PEG-NPs on PDT and photothermal therapy (PTT) could achieve a good performance. Therefore, HE-PEG-NPs could be regarded as a promising phototheranostic agent., (© 2020 Wiley-VCH GmbH.)

FTC dye with a D-π-A structure showed outstanding stability, high extinction coefficient, and good photothermal performance. Thus, nanoparticles based on FTC dye were first fabricated by a nanoprecipitation method for photothermal therapy (PTT) which was guided by photoacoustic imaging (PAI). The prepared FTC NPs showed a photothermal conversion efficiency of ∼52.71%, good photoacoustic performance, and excellent stability in in vitro experiments. Moreover, FTC NPs showed good performance in tumor ablation under a 635 nm laser irradiation and low cytotoxicity to the mice model without laser treatment. Histopathological analysis further confirmed that FTC NPs did not harm the major organs of mice. Given the abovementioned features, FTC NPs have great potential to be effective phototheranostic materials for PAI and PTT.

Carbon dots (CDs), a kind of phototheranostic agent with the capability of simultaneous bioimaging and phototherapy [i.e., photodynamic therapy (PDT) or photothermal therapy (PTT)], have received considerable attention because of their remarkable properties, including flexibility for surface modification, high biocompatibility, low toxicity and photo-induced activity for malignant tumor cells. Among numerous carbon sources, it has been found that natural biomass are good candidates for the preparation of CD phototheranostic agents. In this study, pheophytin, a type of Mg-free chlorophyll derivative and also a natural product with low toxicity, was used as a raw carbon source for the synthesis of CDs by using a microwave method. The obtained hydrophobic CDs exhibited a maximum near-infrared (NIR) emission peak at approximately 680 nm, and high singlet oxygen ( 1 O 2 ) generation with a quantum yield of 0.62. The self-assembled CDs from the as-prepared CDs with DSPE-mPEG2000 retained efficient 1 O 2 generation. The obtained carbon dot assembly was not only an efficient fluorescence (FL) imaging agent but also a smart PDT agent. Our studies indicated that the obtained hydrophilic CD assembly holds great potential as a new phototheranostic agent for cancer therapy. This work provides a new route for synthesis of CDs and proposes a readily available candidate for tumor treatment., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)