Photodynamic therapy(PDT)has been applied in clinical treatment of tumors for a long time.However,insufficient supply of pivotal factors including photosensitizer(PS),light,and oxygen in tumor tissue dramatically redu...Photodynamic therapy(PDT)has been applied in clinical treatment of tumors for a long time.However,insufficient supply of pivotal factors including photosensitizer(PS),light,and oxygen in tumor tissue dramatically reduces the therapeutic efficacy of PDT.Nanoparticles have received an influx of attention as drug carriers,and recent studies have demonstrated their promising potential to overcome the obstacles of PDT in tumor tissue.Physicochemical optimization for passive targeting,ligand modification for active targeting,and stimuli-responsive release achieved efficient delivery of PS to tumor tissue.Various trials using upconversion NPs,two-photon lasers,X-rays,and bioluminescence have provided clues for efficient methods of light delivery to deep tissue.Attempts have been made to overcome unfavorable tumor microenvironments via artificial oxygen generation,Fenton reaction,and combination with other chemical drugs.In this review,we introduce these creative approaches to addressing the hurdles facing PDT in tumors.In particular,the studies that have been validated in animal experiments are preferred in this review over proof-of-concept studies that were only performed in cells.展开更多
Fluorescence imaging has become an essential tool in biomedical research.However,non-invasive deep-tissue threedimensional optical in vivo imaging with the high spatiotemporal resolution is challenging due to the inte...Fluorescence imaging has become an essential tool in biomedical research.However,non-invasive deep-tissue threedimensional optical in vivo imaging with the high spatiotemporal resolution is challenging due to the interaction between photons and tissues.Beam shaping has been used to tailor microscopy techniques to enhance microscope performance.The nearinfrared window(NIR)between 700 and 1,700 nm,generally emphasized as the NIR-II(1,000–1,700 nm)window,has been developed into a promising bio-optical solution chosen as the lower interaction effect in this spectrum,showing potential in basic biological research and clinical application.In this review,we summarize the existing methods to increase penetration depth and extensively describe biological microscopy techniques,NIR-II spectral windows,and fluorophores.Strategies to improve bioimaging performance and NIR-II imaging applications are introduced.Based on the current research achievements,we elucidate the main challenges and provide some recommendations and prospects for deep tissue penetration fluorescence for future biomedical applications.展开更多
Gold nanoparticles(GNPs) are emerging as a novel tool to improve existing cancer therapeutics. GNPs are being used as radiation dose enhancers in radiation therapy as well as anticancer drugs carriers in chemotherapy....Gold nanoparticles(GNPs) are emerging as a novel tool to improve existing cancer therapeutics. GNPs are being used as radiation dose enhancers in radiation therapy as well as anticancer drugs carriers in chemotherapy. However,the success of GNP-based therapeutics depends on their ability to penetrate tumor tissue. GNPs of 20 and 50 nm diameters were used to elucidate the effects of size on the GNP interaction with tumor cells at monolayer and multilayer level. At monolayer cell level, smaller NPs had a lower uptake compared to larger NPs at monolayer cell level. However, the order was reversed at tissue-like multilayer level. The smaller NPs penetrated better compared to larger NPs in tissue-like materials.Based on our study using tissue-like materials, we can predict that the smaller NPs are better for future therapeutics due to their greater penetration in tumor tissue once leaving the leaky blood vessels. In this study, tissue-like multilayer cellular structures(MLCs) were grown to model the post-vascular tumor environment. The MLCs exhibited a much more extensive extracellular matrix than monolayer cell cultures. The MLC model can be used to optimize the nano–micro interface at tissue level before moving into animal models. This would accelerate the use of NPs in future cancer therapeutics.展开更多
Photothermal therapy(PTT)triggered by second near-infrared(NIR-II)light(1000–1400 nm)has shown great potential in tumor ablation because of its good tissue penetrability.However,NIR-II PTT still cannot treat tumors u...Photothermal therapy(PTT)triggered by second near-infrared(NIR-II)light(1000–1400 nm)has shown great potential in tumor ablation because of its good tissue penetrability.However,NIR-II PTT still cannot treat tumors underneath skin because of the light scattering effect of skin components.This research aims to promote the NIR-II penetrability of skin tissue by weakening the light scattering effect from the refractive index inhomogeneity among skin constituents.展开更多
A rapid, sensitive, and robust reversed-phase liquid chromatography with tandem mass spectrometry method was developed and validated for the determination of total and unbound ceritinib, a secondgeneration ALK inhibit...A rapid, sensitive, and robust reversed-phase liquid chromatography with tandem mass spectrometry method was developed and validated for the determination of total and unbound ceritinib, a secondgeneration ALK inhibitor, in patient plasma and brain tumor tissue samples. Sample preparation involved simple protein precipitation with acetonitrile. Chromatographic separation was achieved on a Waters ACQUITY UPLC BEH C_(18) column using a 4-min gradient elution consisting of mobile phase A(0.1% formic acid in water) and mobile phase B(0.1% formic acid in acetonitrile), at a flow rate of 0.4 m L/min. Ceritinib and the internal standard([^(13)C_6]ceritinib) were monitored using multiple reaction monitoring mode under positive electrospray ionization. The lower limit of quantitation(LLOQ) was 1 n M of ceritinib in plasma. The calibration curve was linear over ceritinib concentration range of 1–2000 n M in plasma. The intra-and interday precision and accuracy were within the generally accepted criteria for bioanalytical method( o15%).The method was successfully applied to assess ceritinib brain tumor penetration, as assessed by the unbound drug brain concentration to unbound drug plasma concentration ratio, in patients with brain tumors.展开更多
基金supported by Basic Research Program(2016R1C1B3013951,2021R1F1A1061286,and 2021R1A4A3031875)through the National Research Foundation of Korea(NRF)funded by the Korean government(Ministry of Science,ICT,and Future Planning).
文摘Photodynamic therapy(PDT)has been applied in clinical treatment of tumors for a long time.However,insufficient supply of pivotal factors including photosensitizer(PS),light,and oxygen in tumor tissue dramatically reduces the therapeutic efficacy of PDT.Nanoparticles have received an influx of attention as drug carriers,and recent studies have demonstrated their promising potential to overcome the obstacles of PDT in tumor tissue.Physicochemical optimization for passive targeting,ligand modification for active targeting,and stimuli-responsive release achieved efficient delivery of PS to tumor tissue.Various trials using upconversion NPs,two-photon lasers,X-rays,and bioluminescence have provided clues for efficient methods of light delivery to deep tissue.Attempts have been made to overcome unfavorable tumor microenvironments via artificial oxygen generation,Fenton reaction,and combination with other chemical drugs.In this review,we introduce these creative approaches to addressing the hurdles facing PDT in tumors.In particular,the studies that have been validated in animal experiments are preferred in this review over proof-of-concept studies that were only performed in cells.
基金This work was financially supported by the China Postdoctoral Science Foundation(No.2019M661026)the National Key Research and Development Program of China(No.2021YFF1200700)+3 种基金the National Natural Science Foundation of China(Nos.91859101,81971744,U1932107,814717866,and 11804248)the Natural Science Foundation of Tianjin(Nos.20JCQNJC01270 and 21JCBJC00460)the Public Health Science and Technology Major Project of Tianjin(No.21ZXGWSY00070)the Independent Innovation Foundation Tianjin University(No.2021XT-0018).
文摘Fluorescence imaging has become an essential tool in biomedical research.However,non-invasive deep-tissue threedimensional optical in vivo imaging with the high spatiotemporal resolution is challenging due to the interaction between photons and tissues.Beam shaping has been used to tailor microscopy techniques to enhance microscope performance.The nearinfrared window(NIR)between 700 and 1,700 nm,generally emphasized as the NIR-II(1,000–1,700 nm)window,has been developed into a promising bio-optical solution chosen as the lower interaction effect in this spectrum,showing potential in basic biological research and clinical application.In this review,we summarize the existing methods to increase penetration depth and extensively describe biological microscopy techniques,NIR-II spectral windows,and fluorophores.Strategies to improve bioimaging performance and NIR-II imaging applications are introduced.Based on the current research achievements,we elucidate the main challenges and provide some recommendations and prospects for deep tissue penetration fluorescence for future biomedical applications.
基金the Natural Sciences and Engineering Research Council of Canada(NSERC)Canadian Foundation for Innovation(CFI)
文摘Gold nanoparticles(GNPs) are emerging as a novel tool to improve existing cancer therapeutics. GNPs are being used as radiation dose enhancers in radiation therapy as well as anticancer drugs carriers in chemotherapy. However,the success of GNP-based therapeutics depends on their ability to penetrate tumor tissue. GNPs of 20 and 50 nm diameters were used to elucidate the effects of size on the GNP interaction with tumor cells at monolayer and multilayer level. At monolayer cell level, smaller NPs had a lower uptake compared to larger NPs at monolayer cell level. However, the order was reversed at tissue-like multilayer level. The smaller NPs penetrated better compared to larger NPs in tissue-like materials.Based on our study using tissue-like materials, we can predict that the smaller NPs are better for future therapeutics due to their greater penetration in tumor tissue once leaving the leaky blood vessels. In this study, tissue-like multilayer cellular structures(MLCs) were grown to model the post-vascular tumor environment. The MLCs exhibited a much more extensive extracellular matrix than monolayer cell cultures. The MLC model can be used to optimize the nano–micro interface at tissue level before moving into animal models. This would accelerate the use of NPs in future cancer therapeutics.
基金from the National Natural Science Foundation of China(grant no.21825503).
文摘Photothermal therapy(PTT)triggered by second near-infrared(NIR-II)light(1000–1400 nm)has shown great potential in tumor ablation because of its good tissue penetrability.However,NIR-II PTT still cannot treat tumors underneath skin because of the light scattering effect of skin components.This research aims to promote the NIR-II penetrability of skin tissue by weakening the light scattering effect from the refractive index inhomogeneity among skin constituents.
基金supported by the United States Public Health Service Cancer Center Support Grant P30 CA022453Novartis for providing the study drug and isotope-labeled internal standard and providing financial support for the clinical study
文摘A rapid, sensitive, and robust reversed-phase liquid chromatography with tandem mass spectrometry method was developed and validated for the determination of total and unbound ceritinib, a secondgeneration ALK inhibitor, in patient plasma and brain tumor tissue samples. Sample preparation involved simple protein precipitation with acetonitrile. Chromatographic separation was achieved on a Waters ACQUITY UPLC BEH C_(18) column using a 4-min gradient elution consisting of mobile phase A(0.1% formic acid in water) and mobile phase B(0.1% formic acid in acetonitrile), at a flow rate of 0.4 m L/min. Ceritinib and the internal standard([^(13)C_6]ceritinib) were monitored using multiple reaction monitoring mode under positive electrospray ionization. The lower limit of quantitation(LLOQ) was 1 n M of ceritinib in plasma. The calibration curve was linear over ceritinib concentration range of 1–2000 n M in plasma. The intra-and interday precision and accuracy were within the generally accepted criteria for bioanalytical method( o15%).The method was successfully applied to assess ceritinib brain tumor penetration, as assessed by the unbound drug brain concentration to unbound drug plasma concentration ratio, in patients with brain tumors.
