PHOTOCHEMISTRY AND PHOTOBIOLOGY
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2020
·Vol. 96
·期 5
·1088-1095
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IF 2.721
Lirong Ma,Xuanlin Yang,Xiuzhong Yao,Weiyu Weng
Hexyl aminolevulinate (HAL) is a lipophilic derivative of 5-aminolevulinic acid (5-ALA) and can induce more protoporphyrin IX (PpIX) formation and stronger fluorescence intensity (FI) than 5-ALA, which will greatly facilitate photodynamic diagnosis and therapy. The main drawback of HAL is its low solubility in neutral aqueous media. In this study, surfactants were used to increase HAL solubility in the cell culture medium and serum, followed by in vitro fluorescence formation measurement in human pancreatic cancer cells (SW1990) and in vivo fluorescence detection in tumor-bearing mice. The results showed that Tween 80 (TW80) and Kolliphor® HS 15 (HS15) increased the solubility of HAL in the selected media. Although TW80 and HS15 exhibited in vitro cytotoxicity at high concentrations (5 mg mL −1 ), they facilitated fluorescent signal formation at the early stage of cell incubation. When surfactants were used, the FI should be determined without the routine washing process because surfactant-containing culture medium caused the loss of synthesized PpIX during the washing process. When HAL dissolved in TW80 solution was injected intraperitoneally into pancreatic cancer-bearing mice at a dose of 50 mg kg −1 , the tumors exhibited red fluorescence, which indicated that systemic administration of surfactant-solubilized HAL might be applicable for tumor fluorescence detection in vivo .
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BIOMATERIALS
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2020
·
IF 10.317
Shi-Bo Wang,Zhao-Xia Chen,Fan Gao,Cheng Zhang,Mei-Zhen Zou,Jing-Jie Ye,Xuan Zeng,Xian-Zheng Zhang
Photodynamic therapy (PDT) is a promising treatment modality for tumor suppression. However, the hypoxic state of most solid tumors might largely hinder the efficacy of PDT. Here, a functional covalent organic framework (COF) is fabricated to enhance PDT efficacy by remodeling the tumor extracellular matrix (ECM). Anti-fibrotic drug pirfenidone (PFD) is loaded in an imine-based COF (COF TTA-DHTA ) and followed by the decoration of poly(lactic-co-glycolic-acid)-poly(ethylene glycol) (PLGA-PEG) to fabricate PFD@COF TTA-DHTA @PLGA-PEG, or PCPP. After injected intravenously, PCPP can accumulate and release PFD in tumor sites, leading to down-regulation of ECM compenents such as hyaluronic acid (HA) and collagen I. Such depletion of tumor ECM reduces the intratumoral solid stress, a compressive force exerted by the ECM and cells, decompresses tumor blood vessels, and increases the density of effective vascular areas, resulting in significantly improved oxygen supply in tumor. Furthermore, PCPP-mediated tumor ECM depletion also enhances the tumor uptake of subsequently injected Protoporphyrinl IX (PPIX)-conjugated peptide formed nanomicelles (NM-PPIX) due to the improved enhanced permeability and retention (EPR) effect. Both the alleviated tumor hypoxia and improved tumor homing of photosensitizer (PS) molecules after PCPP treatment significantly increase the reactive oxygen species (ROS) generation in tumor and therefore realize greatly enhanced PDT effect of tumor in vivo.
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Frontiers in Chemistry
·
2019
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IF 3.782
Fan Jing Hao,Fan Gui Ling,Yuan Ping,Deng Fu An,Liu Ling Shan,Zhou Xiang,Yu Xi Yong,Cheng Hong,Li Shi Ying
Hypoxia is a common feature for most malignant tumors, which was also closely related to the oxygen-dependent photodynamic therapy. Based on Förster resonance energy transfer (FRET), a smart nanoprobe (designated as H-Probe) was designed in this paper for hypoxia imaging and photodynamic tumor therapy. Due to the FRET process, H-Probe could respond to hypoxia with a significant fluorescence recovery. Moreover, abundant in vitro investigations demonstrated that the photosensitizer of PpIX in H-Probe could generate large amounts of singlet oxygen to kill cancer cells in the presence of oxygen and light with appropriate wavelength. Also, intravenously injected H-Probe with light irradiation achieved an effective tumor inhibition in vivo with a reduced side effect. This original strategy of integrating hypoxia imaging and tumor therapy in one nanoplatform would promote the development of theranostic nanoplatform for tumor precision therapy.
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ACS Sustainable Chemistry & Engineering
·
2019
·
IF 6.97
Junfan Niu,Jingyue Tang,Gang Tang,Zhiyuan Zhou,Rong Tang,Jiale Yang,Na Jiang,Jianqiang Li,Yongsong Cao
Photosensitizers need to be activated by external light to achieve phototherapy. However, unsatisfactory tissue penetration of light and uncontrollable light intensity limit their application. To overcome the limitations, a novel fluorescent conjugate was developed by conjugating coumarin-functionalized nanosilica with acifluorfen to emit fluorescence as the supplementary light to activate protoporphyrin IX (PpIX, a photosensitizer in plant cell that can be induced by acifluorfen) for enhancing phototherapy activity. The results showed that the obtained conjugate could obviously increase the singlet oxygen yield of PpIX and exhibited remarkable photodynamic herbicidal activity against Amaranthus retroflexus. Under low light intensity, its photodynamic herbicidal activity was five to six times higher than that of acifluorfen sodium salt. The conjugate could move upward and downward freely in vascular system of Brassica juncea seedlings and significantly reduced the cytotoxicity of acifluorfen. Moreover, the conjugate was proved to be safe to soybean at concentrations of 200–800 mg/L of acifluorfen. This study gives a novel drug delivery system with the potential of reducing light-dependent drug dosage and harm to nontarget organisms and offers a way to use fluorescent emission as the supplementary light to enhance the phototherapy activity of photosensitizers.
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JOURNAL OF APPLIED POLYMER SCIENCE
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2022
·Vol. 140
·期 7
·e53485
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IF 3.057
Jiahao Shi,Zhengnan Lu,Yan Pan,Yang Sheng,Yixin Sun,Linhong Deng,Mark Bradley,Le Zhou,Rong Zhang
Protoporphyrin IX (PpIX) is a photosensitizer used in photodynamic therapy, however, its poor aqueous solubility always presents challenges and limits its application. To solve these problems water-soluble derivatives of PpIX were synthesized by esterification with polyethylene glycol, and polymerization of the PpIX diol with hexamethylene diisocyanate to form a water-soluble polyurethane. The polyurethane PpIX derivatives were characterized and showed high levels of singlet oxygen generation. The photodynamic antibacterial activity of the PpIX derivatives were explored on Escherichia coli , Staphylococcus aureus and methicillin-resistant Staphylococcus aureus indicated that 100% antibacterial killing was achieved with a concentration of 40 μM upon 405 nm irradiation for 5 min. The polyurethane showed high biocompatibility in the dark with a variety of cell lines, but when exposed to 405 nm light (for 5 min) cytotoxic singlet oxygen was generated, resulting in cell death. Importantly, this was also possible with 635 nm illumination. In summary this novel protoporphyrin polyurethane overcomes the issues of solubility, and offers enhanced killing (singlet oxygen) generation with the potential to be used in photodynamic therapy for both antibacterial and anticancer treatment.
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IEEE PHOTONICS TECHNOLOGY LETTERS
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2022
·Vol. 34
·期 12
·661-664
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IF 2.414
Tianfeng Wang,Jianfei Dong
Anti-fungal blue light (ABL) therapies are based on the photochemical reaction of endogenous photosensitizer (PS) in fungal cells. Knowing the spectral sensitivity of these cells for the ability to generate singlet oxygen is thus important to determine the most effective wavelength of such light therapies, and thereby to design ABL therapeutic devices, e.g., by light emitting diodes. We propose a modeling method of such spectral sensitivity in this work, based on the absorption spectra of cells and other inherent characteristic parameters, i.e., singlet oxygen quantum yield and the extinction coefficient of the endogenous PS. Specifically, the absorption spectra are determined by the PSs inside the fungus Candida albicans and human epithelial cells. Then, the concentration of PS in those two types of cells was measured by high-performance liquid chromatography (HPLC) assays. The HPLC assays show that the coproporphyrin (CP) is the main PS in C. albicans, accounting for 60% of the total PS. The simulation results demonstrate that the 390~420nm light can stimulate the PS in the cells to generate more singlet oxygen in C. albicans than in epithelial cells; and this range is the same as the CP Soret band. In contrast, the light with wavelengths >450nm is less effective in exciting the PS in C. albicans, and leads to more singlet oxygen generation in V.E. cells than shorter wavelength. We thus conclude that 390~420nm light is the most effective range for inhibiting C. albicans with the least damage to human host cells.
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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2023
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IF 5
Yun Liu,Qian Lan,Jinxiu Liu,Yaxin Shi,Quanxin Wu,Qian Wang,Shuang Yang,Fan Cheng
To avoid the occurrence of antibiotic resistance and improve bactericidal effect, a multifunctional antibacterial nanoagent BCPP was successfully constructed for targeted photodynamic/photothermal combination therapy (PDT/PTT). The prepared BCPP consists of protoporphyrin (PpIX) as the photosensitizer , CuS nanoparticles as the photothermal agent, phenylboric acid (PBA) as the bacteria-targeting segment and bovine serum albumin (BSA) as the colloid stabilizer. Afterwards, its photodynamic/photothermal capacities, bacteria-targeting effect and bactericidal efficiency were intensively investigated. Experimental results confirmed its good singlet oxygen generation ability and high photothermal conversion efficiency. In addition, BCPP displayed good bacteria-targeting properties for both S. aureus and E. coli . Moreover, in vitro antibacterial assays proved its enhanced therapeutic efficiency through combined antibacterial PDT/PTT owing to PBA-mediated bacteria-targeting function. Finally, in vitro assays revealed its good hemocompatibility and low cytotoxicity. To sum up, our study offered a convenient method to build non-antibiotic antibacterial nanoagents for targeted PDT/PTT, and the prepared bactericidal is a promising drug candidate suitable for clinical trials in the future.
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JOURNAL OF PHYSICAL CHEMISTRY B
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2023
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IF 3.3
Lu Li,Meng Kou,Yongda Wang,Feng Qin,Hua Zhao,Zhiguo Zhang
The oxygen-varying correlated fluorescence provides an effective strategy to gain the quenching constant KSV for a non-phosphorescent system. Owing to the absence of detectable phosphorescence emission in general optical spectroscopy, the facticity of this method has never been verified. Here, the correct way to determine KSV by oxygen-varying correlated fluorescence was systematically studied in detail. We selected gadolinium protoporphyrin IX (Gd-PpIX) to establish a fluorescence and phosphorescence dual emission system. Then, KSV of Gd-PpIX can be obtained by the change of fluorescence intensity (IF) with oxygen concentration using the method of correlated fluorescence at intense pump power; meanwhile, the value can also be determined from the relationship of the phosphorescence intensity ratio and oxygen content by the Stern–Volmer equation under relatively low power density. It was found that the KSV values obtained by the above two methods were 12.2(1) and 11.9(7) kPa–1, respectively. Our results successfully verified the accuracy of oxygen-varying correlated fluorescence for determining the KSV by the phosphorescence property and fluorescence saturation of Gd-PpIX.
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SENSORS AND ACTUATORS B-CHEMICAL
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2023
·
IF 8.4
Yongda Wang,Zheng Hu,Jia Li,Yunhan Zhao,Meng Kou,Feng Qin,Zhiguo Zhang
A dual-excitation laser modulation technique for the sensitive measurement of photosensitizers in tumor is proposed. The technique is based on the difference in optical absorption properties of photosensitizers and biological tissues at 405 nm and 450 nm. The 405 nm and 450 nm laser beams, with the same modulation frequency and 180° phase difference, were coupled into a single fiber simultaneously. A periodic signal with a frequency of 1 kHz was generated in alternating excitation, and was processed by phase sensitive detectors. The weak photosensitizer fluorescence masked by tissue autofluorescence can be effectively separated through the proposed method, so that the final signal intensity is only related to the concentration of photosensitizer. The method with a sensitivity of 0.22 mL/ng was determined by measuring the low concentration of protoporphyrin IX (PpIX) solution, and the detection limit of instrument reached 0.5 ng/mL. The puncturable optical probe with a diameter of 675 µm ensures that PpIX in can be detected with spatial resolution, which was performed in the measurement of PpIX in tumor bearing nude mice .
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Biosensors-Basel
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2023
·Vol. 13
·期 4
·489
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IF 5.4
Jiawen Han,Yaru Ding,Xujuan Lv,Yuwei Zhang,Daoqing Fan
The effective and accurate detection of the anticancer drug coralyne (COR) is highly significant for drug quality control, medication safety and good health. Although various COR sensors have been reported in recent years, previous ones can only exhibit single-signal output (turn ON or turn OFF) with poor reliability and anti-interference ability. Therefore, exploring novel platform with dual-signal response for COR detection is urgently needed. Herein, we reported the first ratiometric fluorescent platform for highly sensitive and selective COR detection by integrating G-quadruplex (G4) and Pyrene (Py) as signal probes and harnessing A-COR-A interaction. In the absence of COR, the platform shows a low fluorescence signal of PPIX (F642) and a high one of Py monomer (F383). With the addition of COR, two delicately designed poly-A ssDNAs will hybridize with each other via A-COR-A coordination to form complete G4, yielding the increased fluorescence signal of PPIX and the decreased one of Py due to the formation of Py excimer. Based on the above mechanism, we constructed a simple and efficient sensor that could realize the ratiometric fluorescent detection of COR with high sensitivity and selectivity. A linear relationship between F642/F383and COR’s concentration is obtained in the range from 1 nM to 8 μM. And the limit of detection of COR could reach to as low as 0.63 nM without any amplification, which is much lower than that of most COR sensors reported so far. Notably, the logical analysis of COR can be carried out under the control of a “YES-NOT” contrary logic pair, enabling the smart dual-channel response with an adequate S/N ratio and improved reliability and anti-interference ability. Moreover, this system also presents satisfactory performance in fetal bovine serum (FBS) samples.Keywords:ratiometric fluorescence;coralyne detection;contrary logic pair;G-quadruplex;anticancer drug
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JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2023
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IF 9.9
Jie An,Xinyi He,Huizhu Ma,Yanglei Li,Yayuan Li,Xinyu Zhang,Qizhi Shuai,YinMeng Wang,Wen Liu,Weihua Li,Hongliang Wang,Zhifang Wu,Sijin Li
Radionuclide therapy (RNT) is an effective method for the clinical precise treatment of cancer. However, the uneven dose distribution and rapid metabolism of nuclides limit the effective killing of tumors. To overcome the limitations of radionuclide therapeutic approaches, combining different therapeutic strategies to treat cancer has manifested great promise in basic and clinical research. Here, a new combination therapy strategy was developed to combine radionuclide therapy, sonodynamic therapy and photothermal therapy (RNT-SDT-PTT) under radionuclide imaging guided achieve highly effective combination therapy. We prepared a polydopamine-modified Au nanostar (AN), then loaded with the acoustic sensitizer protoporphyrin (IX) and labeled with diagnostic ( 99m Tc) or therapeutic ( 131 I) radionuclides ( 131 I/ 99m [email protected] /IX) for the precise diagnosis and treatment of pancreatic cancer. After intratumor administration, single photon emission computed tomography imaging showed that the nanocarriers were mostly retained in the tumor compared to free radionuclide. As well as using near-infrared light to trigger PTT and ultrasound with high penetration depth to activate IX to generate reactive oxygen species achieved SDT of tumor. The ultimate significantly improved the inhibitory effects by the RNT-SDT-PTT combined therapy for pancreatic cancer. Therefore, this study proposes an effective radionuclide combination therapy regimen consisting of three widely used treatments, offering promising prospects for the future of oncology.
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Acta Biomaterialia
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2023
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IF 9.7
Kang Song,Guobo Chen,Zongyan He,Jing Shen,Jing Ping,Yuhao Li,Lulu Zheng,Yuqing Miao,Dawei Zhang
Decreasing the scavenging capacity of reactive oxygen species (ROS) and enhancing ROS production are the two principal objectives in the development of novel sonosensitizers for sonodynamic therapy (SDT). Herein, we designed a protoporphyrin-sensitized bismuth-based semiconductor (P-NBOF) as a sonosensitizer to generate ROS and synergistically depleted glutathione for enhanced SDT against tumors. The bismuth-based nanomaterial (NBOF) is a wide-bandgap semiconductor. Sensitization by protoporphyrin made it easier to excite electrons under ultrasonic stimulation, and the energy of the lowest unoccupied electron orbital in protoporphyrin was higher than the conduction-band energy of NBOF. Under ultrasound excitation, the excited electrons in the protoporphyrin were injected into the conduction band of the NBOF, increasing its reducing ability leading to the production of more superoxide anion radicals and also helping to increase the charge separation of protoporphyrin leading to the production of more singlet oxygen. Meanwhile, P-NBOF continuously depleted glutathione, which was not only conducive to breaking the redox balance of the tumor microenvironment to enhance the therapeutic efficacy of SDT, but also promoted its degradation and metabolism. The construction of this P-NBOF sonosensitizer thus provided an effective strategy to enhance SDT for tumors. Statement of significance To enhance the efficacy of sonodynamic tumor therapy, we developed a degradable protoporphyrin-sensitized bismuth-based nano-semiconductor (P-NBOF) by optimizing the band structure and glutathione-depletion ability. Protoporphyrin in P-NBOF under excitation preferentially generates free electrons, which are then injected into the conduction band of NBOF, improving the reducing ability of NBOF and promoting the separation of electron-hole pairs, thereby enhancing the production capacity of reactive oxygen species. Furthermore, P-NBOF can deplete glutathione, reduce the scavenging of reactive oxygen species, and reactivate and amplify the effect of sonodynamic therapy. The construction of the nanotherapeutic platform provides an option for enhancing sonodynamic therapy.
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