Abstract Given that type I photosensitizers (PSs) possess a good hypoxic tolerance, developing an innovative tactic to construct type I PSs is crucially important, but remains a challenge. Herein, we present a smart molecular design strategy based on the Förster resonance energy transfer (FRET) mechanism to develop a type I photodynamic therapy (PDT) agent with an encouraging amplification effect for accurate hypoxic tumor therapy. Of note, benefiting from the FRET effect, the obtained nanostructured type I PDT agent (NanoPcSZ) with boosted light‐harvesting ability not only amplifies superoxide radical (O 2 •‐ ) production but also promotes heat generation upon near‐infrared light irradiation. These features facilitate NanoPcSZ to realize excellent phototherapeutic response under both normal and hypoxic environments. As a result, both in vitro and in vivo experiments achieved a remarkable improvement in therapeutic efficacy via the combined effect of photothermal action and type I photoreaction. Notably, NanoPcSZ can be eliminated from organs (including the liver, lung, spleen, and kidney) apart from the tumor site and excreted through urine within 24 h of its systemic administration. In this way, the potential biotoxicity of drug accumulation can be avoided and the biosafety can be further enhanced.
Abstract A pH‐responsive nanohybrid (LDH–ZnPcPS 4 ), in which a highly hydrophilic zinc(II) phthalocyanine tetra‐α‐substituted with 4‐sulfonatophenoxy groups (ZnPcPS 4 ) is incorporated with a cationic layered double hydroxide (LDH) based on electrostatic interaction, has been specially designed and prepared through a facile co‐precipitation approach. ZnPcPS 4 is an excellent singlet‐oxygen generator with strong absorption at the near‐infrared region (692 nm) in cellular culture media, whereas the photoactivities of ZnPcPS 4 were remarkably inhibited after incorporation with the LDH. The nanohybrid is essentially stable in aqueous media at pH 7.4; nevertheless, in slightly acidic media of pH 6.5 or 5.0, ZnPcPS 4 can be efficiently released from the LDH matrix, thus leading to restoration of the photoactivities. The nanohybrid shows a high photocytotoxicity against HepG2 cells as a result of much more efficient cellular uptake and preferential accumulation in lysosomes, whereby the acidic environment leads to the release of ZnPcPS 4 . The IC 50 value of LDH–ZnPcPS 4 is as low as 0.053 μ M , which is 24‐fold lower than that of ZnPcPS 4 . This work provides a facile approach for the fabrication of photosensitizers with high photocytotoxicity, potential tumor selectivity, and rapid clearance character.
A simple, one-pot process for the construction of substituted spiro[5,5]undecane-1,5,9-triones using aromatic aldehydes and Meldrum’s acid, and aniline as a catalyst, is reported. Fifteen compounds were synthesized, and the trans/cis ratios were calculated based on 1H NMR analyses of the unpurified products. Quantum mechanical calculations and X-ray diffraction were undertaken to identify the configuration of compound 2a. The proposed mechanisms for these reactions are presented in this paper. In contrast to previous literature, this method endows excellent diastereoselectivity to a series of trans-substituted derivatives. The method is characterized by its simple operation, commercial availability of all materials, mild reaction conditions and moderate-to-good chemical yields.
Nanoparticle-based enzyme mimics have fewer applications in ferrotherapy so far. The limited number of integrated biomimetic architectures satisfy biobuilding blocks and adaptability in the high efficiency of ferrotherapy requirements. Herein, we develop a minimal nanoparticle as an efficient photodynamic ferrotherapy agent, which is constructed through ferrous-coordination-driven cyanine-based amino acid assembly. In comparison with a free photosensitizer, this nanoparticle (photofenozyme) composed of Fe-containing cores and serum protein shells is fabricated. And it has a high light-harvesting ability, and a higher intersystem crossing (ISC) rate constant (4.41 × 1011 s–1 versus 1.17 × 106 s–1), which benefits efficient production of the triplet state. The photofenozyme allows adaptive photo-Fenton-like activity based on the different radical generations. And they further trigger and photoenhance efficient ferroptosis. This work provides insights into optimizing current photosensitizers to generate an adaptive supramolecular photocatalyst and presents a promising strategy to design multifunctional nanozyme theranostics.
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
The high penetration depth of sonodynamic therapy (SDT) and the instantaneous opening of the blood–brain barrier (BBB) due to ultrasound stimulation make SDT superior for treating gliomas. Here, we construct amphiphilic cationic phthalocyanine (ZnPc) and combine it with human serum albumin (HSA) to create a ZnPc–HSA supramolecular complex through green synthesis. The urgent need for energy to achieve rapid tumor growth and the strong expression of the albumin binding-related protein gives ZnPc–HSA the ability to cross the BBB and enrich gliomas. Moreover, this complex increases the biocompatibility and penetration depth (by approximately 1.75 times) and enhances reactive oxygen species generation (by approximately 16.54 times) after ultrasound stimulation. Further, ZnPc–HSA-based SDT effectively inhibits the growth of gliomas in diseased mice and prolongs their lifetime. This study provides a promising platform for future construction of supramolecular biomimetic nanomaterials for SDT to treat brain disorders.
Photoacoustic imaging has begun to be widely used to observe drug delivery and accumulation in the body. Theranostic, which includes both diagnosis and therapy, is an attractive approach for treating cancer. In this study, we synthesized nanomaterials and verified the theranostic effect through fluorescence and photoacoustic imaging. Selectively transporting a drug to the tumor site is essential to increase the therapeutic effect while reducing side effects. BODIPY has the advantages of being able to change its structure more easily, good photostability, good biocompatibility and high absorption coefficient than cyanine or porphyrin dyes, however they are limited to in vivo experiment due to their poor water solubility. We overcome the limitations of BODIPY-based materials by encapsulating in micellar nanoparticles with Hexa BODIPY cyclophosphazene (HBCP) and DSPE-PEG2000 polymer. HBCP NPs also have a property of selectively accumulating in tumors with enhanced permeability and retention effect due to their bulky nano-size molecular structure. We checked the tumor targeting and retention time of HBCP NPs by monitoring them with fluorescence imaging. In addition, the high heat conversion efficiency of HBCP NPs enables photoacoustic imaging and Photothermal therapy. We also conducted whole body scanning of tail-vein injected tumor-bearing mice with acoustic resolution photoacoustic microscopy system to provide tumor accumulation information of HBCP NP with vascular structure. The result suggests that HBCP NP has a potential to be used as a material for image guided phototherapy.
Abstract Given that type I photosensitizers (PSs) possess a good hypoxic tolerance, developing an innovative tactic to construct type I PSs is crucially important, but remains a challenge. Herein, we present a smart molecular design strategy based on the Förster resonance energy transfer (FRET) mechanism to develop a type I photodynamic therapy (PDT) agent with an encouraging amplification effect for accurate hypoxic tumor therapy. Of note, benefiting from the FRET effect, the obtained nanostructured type I PDT agent (NanoPcSZ) with boosted light‐harvesting ability not only amplifies superoxide radical (O 2 •‐ ) production but also promotes heat generation upon near‐infrared light irradiation. These features facilitate NanoPcSZ to realize excellent phototherapeutic response under both normal and hypoxic environments. As a result, both in vitro and in vivo experiments achieved a remarkable improvement in therapeutic efficacy via the combined effect of photothermal action and type I photoreaction. Notably, NanoPcSZ can be eliminated from organs (including the liver, lung, spleen, and kidney) apart from the tumor site and excreted through urine within 24 h of its systemic administration. In this way, the potential biotoxicity of drug accumulation can be avoided and the biosafety can be further enhanced.
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