JOURNAL OF FOOD SCIENCE
·
2025
·Vol. 90
·期 3
·e70075
·
IF 3.4
Xuefeng Qu,Qinxi Wang,Zemi Xie,Yuejin Wu,Yangjunna Zhang,Zhen Liu,Yin Wang
The Chlamydomonas reinhardtii (red) is a strain rich in protoporphyrin IX, which could be used as algal-derived novel sustainable nutritional sources. However, the safety research on C. reinhardtii (red) remains insufficient and further investigation is needed. In order to assess the safety of C. reinhardtii (red) and to expand its use in food applications, a series of toxicological safety evaluations were carried out to observe acute toxicity, subchronic toxicity and genotoxicity of C. reinhardtii (red). The C. reinhardtii (red) was administered to an acute oral toxicity test, mammalian micronucleus test, mouse chromosomal aberration test in Institute of Cancer Research (ICR) mice, and 90-day repeated-dose oral toxicity test in Sprague-Dawley (SD) rats. In the acute oral toxicological test, no mortality or abnormalities were observed in male and female rats, with an median lethal dose(Lethal Dose, 50%) (LD 50 ) exceeding 10.0 g/kg body weight (BW). Similarly, male and female mice exhibited no mortality or abnormalities, with an LD 50 surpassing 20.0 g/kg BW. The results of bacterial reverse mutation test, mammalian micronucleus test, and mouse chromosomal aberration test were all negative, suggesting that the C. reinhardtii (red) did not show mutagenicity under the conditions of this experiment. In a 90-day repeated-dose oral toxicity study, the SD rats were orally administered daily doses of 2.0 g/kg BW, 4.0 g/kg BW, and 8.0 g/kg BW without exhibiting any signs or symptoms of toxicity. Therefore, the no observed adverse effect level (NOAEL) of C. reinhardtii (red) was 8.0 g/kg BW/day. This study contributes to information necessary to form a basis for safety for expanding the application range of C. reinhardtii (red) in food. Practical Application The aim of this study was to assess the safety of C. reinhardtii (red) and to expand its use in food applications. The major finding of this study is that the C. reinhardtii (red) did not show acute toxicity, subchronic toxicity and genotoxicity under the conditions of this experiment. This study contributes to information necessary to form a basis for safety for expanding the application range of C. reinhardtii (red) in food.
研究领域:
毒理学
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食品安全
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营养学
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DOI
PubMed
高影响因子
JOURNAL OF APPLIED POLYMER SCIENCE
·
2022
·Vol. 140
·期 7
·e53485
·
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.
研究领域:
生物化学
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材料科学
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医学
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DOI
高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
·
2025
·
IF 2.5
Yang Sheng,Kangyao Zhao,Yang Liu,Peng Zhang,Yixin Sun,Rong Zhang
Photodynamic therapy (PDT) is a promising strategy for cancer treatment. However, the poor hydrophilicity of most photosensitizers makes them difficult to enter the cells and also susceptible to aggregation-induced quenching in aqueous environment. In this study, we encapsulated protoporphyrin IX (PPIX) by nanostructured lipid carrier to obtain a water-soluble PPIX delivery system (NLC-PPIX). The nanoparticles exhibited high colloidal stability and good fluorescence emission. The generation of 1O2 from the NLC-PPIX was verified using 9,10-anthracenediyl-bis(methylene)dicarboxylic acid (ABDA) as 1O2 indicator. The 1O2 quantum yield of the NLC-PPIX in aqueous solution was calculated to be ∼9%. The flow cytometry and fluorescence imaging confirmed the uptake of NLC-PPIX by the A2058 cells and the generation of 1O2 inside the cells under light excitation. The in vitro cytotoxicity assay showed that the NLC-PPIX exerted no toxicity on the A2058 cells under dark conditions, while light irradiation triggered high phototoxicity. The cell viability of the A2058 cells was significantly decreased and the inhibition rate reached approximately 96% by treating the cells with 200 μg/mL NLC-PPIX and 420 nm light irradiation. The successful cancer cell uptake and PDT effect revealed the therapeutic promise of our drug delivery system.
研究领域:
药剂学
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肿瘤学
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生物医学工程
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DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2020
·
IF 5.88
Tingting Wang,Huizhen Ke,Shiping Chen,Jian Wang,Wushi Yang,Xiuming Cao,Jingyan Liu,Qufu Wei,Reza A. Ghiladi,Qingqing Wang
Motivated by the need for self-disinfecting materials that can be used to reduce the surface transmission of harmful microbes to healthy hosts, here we prepared a photodynamic antimicrobial membrane comprised of electrospun cellulose diacetate (CA) microfibers into which the photosensitizer protoporphyrin IX (PpIX) was in situ embedded. The resultant porous PpIX-embedded CA (PpIX/CA) microfibrous membranes were prepared with two different photosensitizer loadings: 5 and 10 wt% PpIX with respect to CA (85 and 170 nmol PpIX/mg membrane, respectively). The singlet oxygen ( 1 O 2 ) generated by the embedded photosensitizer was confirmed by electron paramagnetic resonance spectroscopic studies through generation of the TEMPO radical, and its photooxidation efficiency was further investigated using potassium iodide as a model substrate. Antibacterial photodynamic inactivation studies showed that the PpIX/CA membrane achieved a 99.8% reduction in Gram-positive S . aureus after illumination (Xe lamp, 65 ± 5 mW/cm 2 , λ ≥ 420 nm; 30 min), with a lower level of reduction (86.6%) for Gram-negative E . coli . Potentiation with potassium iodide was found to be an effective way to further enhance the antimicrobial efficacy of the PpIX/CA microfibrous membrane, achieving 99.9999% (6 log units) inactivation of both S . aureus and E . coli in the presence of 25 and 100 mM KI, respectively. These findings indicate that the electrospun CA microfibrous membrane is an ideal matrix for a photosensitizer such as PpIX to be embedded and effectively sensitized upon visible light illumination, and its antimicrobial photodynamic inactivation efficiency could be strongly enhanced with the increased KI addition, showing a promising future for its use in pathogen transmission defensive materials.
研究领域:
材料科学
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微生物学
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光动力疗法
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DOI
PubMed
高影响因子
Food Bioscience
·
2024
·
IF 4.8
Ying Wu,Feiran Xu,Lingjie Kong,Xiaomin Li,Liangmin Wei,Baocai Xu
In this study, we investigated cooked hams to understand the relationship between display life and quality changes, as well as the microbiological characteristics of refrigerated storage for up to 90 days. Initially, the L* and a* values exhibited an initial decline with a gradual restitution to levels insignificantly disparate from those Day 15 hams. In contrast, the b* and h° values demonstrated an ascending pattern, indicating an augmentation in yellow intensity during the storage. Furthermore, there was an observable escalation in the C* value following 45 days of storage, implying an amplified luminosity and vividness of color during the latter phase of the storage period. Analyses of TBARS , TVB-N, and other physicochemical indexes indicated that the hams underwent deterioration during storage. Whereas, UV–vis and fluorescence spectroscopy illustrated that the pigment in cooked hams changed from nitrosylheme (NO-heme) to Zn-protoporphyrin IX (ZnPP) during storage. The NO-heme content decreased from 41.08 ± 0.44 to 12.76 ± 0.29 mg/kg, while the ZnPP content increased from 12.19 ± 0.41 to 89.44 ± 1.57 mg/kg. The structure of the bacterial community in the ham samples changed over the storage period. Towards the end of the shelf life, the microbial population was dominated by Lactic acid bacteria (LAB), particularly Latilactobacillus (34.91%) and Leuconostoc (19.73%). Redundancy analysis and Pearson correlation revealed a positive correlation between Latilactobacillus and Leuconostoc with TBARS , TVB-N, ZnPP content, and negative correlations with Aw and NO-heme.
研究领域:
食品科学
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微生物学
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DOI
高影响因子
ACS Omega
·
2021
·
IF 3.512
Yun Wang,Min Gong,Zhuo Huang,Hai Min,Peng Yu,Fuzhou Tang,Yuannong Ye,Simian Zhu,Zuquan Hu,Zhu Zeng,Jin Chen
Hematoporphyrin (HP) and protoporphyrin IX (PPIX) are useful porphyrin photosensitizers with significant application values in photodynamic therapy. Currently, many strategies have been developed to improve their clinical performance, such as incorporating them with nanoparticle (NP) carriers. In this work, we studied the possibility of using β-lactoglobulin (BLG) as a potential NP carrier due to their hydrophobic affinity, pH sensitivity, and low cost of extraction and preservation. The interaction mechanisms of BLG with HP and PPIX were investigated using spectroscopic techniques and molecular docking methods. The molecular docking results agree well with the experimental results, which demonstrate that the formations of HP-BLG and PPIX-BLG complexes are endothermic processes and the main acting force is hydrophobic force. Furthermore, the opening–closure states of EF loop have a great influence on the HP-BLG complex formation, where the central hydrophobic cavity of β-barrel is available for HP binding at pH 7.4 but not available at pH 6.2. However, the formation of the PPIX-BLG complex is less dependent on the states of the EF loop, and the binding sites of PPIX are both located on the external surface of BLG under both pH 7.4 and 6.2 conditions. All of our results would provide new insight into the mechanisms of noncovalent interactions between BLG and HP/PPIX. It is believed that this work indicated the potential application values of BLG in designing pH-sensitive carriers for the delivery of HP and PPIX, as well as other poorly soluble drugs.
研究领域:
生物化学
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药物递送
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光动力治疗
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2020
·
IF 4.225
Lv Jinpeng,An Xiaohong,Jiang Songzhou,Yang Ying,Song Guoqiang,Gao Rongyin
Protoporphyrin IX (PPIX) is a heterocyclic organic compound that is the last intermediate in the heme biosynthetic pathway. PPIX, due to its photodynamic effects, is utilized in the treatment of skin diseases. Furthermore, PPIX has been utilized as a melanogenesis-stimulating agent in various studies. However, the exact function and mechanism underlying PPIX action in melanocytes remain to be elucidated. In the present study, we sought to further investigate how PPIX affects melanocyte melanogenesis, and whether PPIX is involved in melanin transport. Our findings demonstrated that PPIX increased melanocyte dendricity and melanosome transport, in addition to increasing melanogenesis. PPIX functions primarily by activating the guanylate cyclase (GC) and cyclic guanosine 3’, 5’-monophosphate/protein kinase G (cGMP/PKG) signaling pathways. Once activated, these pathways increase tyrosinase activity and the expression of microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 and -2 (TRP-1 and TRP-2), myosin Va, melanophinin, Ras-related protein Rab-27A (Rab27a), and cell division cycle 42 (Cdc42), promoting melanogenesis, melanocyte dendricity, and melanosome transport. Furthermore, the melanogenic effects of PPIX were confirmed in vivo in a zebrafish model system. Our results indicate that PPIX is not cytotoxic and may, thus, be utilized as a pigmentation enhancer.
研究领域:
细胞生物学
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分子生物学
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药理学
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皮肤病学
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DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2016
·
IF 5.886
Hanjun Cheng,Xuefeng Qiu,Xiaozhi Zhao,Wei Meng,Da Huo,Hui Wei
Parallel monitoring of K+ and protoporphyrin IX (PPIX) is of vital importance because they are not only involved in a variety of biological processes but also closely linked to each other in numerous cellular pathways. However, there are currently no existing methods that can meet the requirements for parallel and in vivo detection of K+ and PPIX in living organisms. Herein, we demonstrated a functional nucleic acid (FNA)-based technique for parallel monitoring of K+ and PPIX in living animals. Specifically, the selected G-rich FNA probe was selectively induced to form a parallel G-quadruplex by K+. The parallel G-quadruplex then remarkably enhanced the fluorescence of PPIX. Thus, by modulating the fluorescence “turn on” with the G-quadruplex and K+/PPIX, both K+ and PPIX could be detected. After validating the developed method for selective and sensitive detection of K+ and PPIX in vitro, their dynamic changes in living organisms (i.e., living brains and tumors) following various physiological and pathological processes were simultaneously monitored. The current study not only provides a general method for the detection of metal ions and bioactive molecules but also presents a way to investigate their synergistic functions in the regulation of various biological processes. It may also be helpful for improving the imaging and therapeutic efficacy of PPIX and 5-ALA.
研究领域:
生物化学
·
分子生物学
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生物医学工程
·
分析化学
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DOI
PubMed
高影响因子
EUROPEAN POLYMER JOURNAL
·
2022
·
IF 5.546
Jinsheng Liu,Zhuoer Dai,Pingkai Shen,Yihua Yin,Yin Yi,Weiquan Cai,Lihong Fan,Guanghua He,Jingli Zhang,Wenjin Xu,Silin Chen,Jiayi Pan
To enhance bacteria-targeting and improve bactericidal activity, a novel GSH-responsive photodynamic antimicrobial nanosystem based on Alginate oligosaccharide-protoporphyrin IX (AOS-ss-PpIX) conjugates were constructed. The fluorescence self-quenching caused by the aggregation of PpIX groups into hydrophobic core could promote the photostability of PpIX and avoid the phototoxicity of the non-infected sites of the target plants. But once exposed to GSH stimulus, the recovery of high photodynamic activity were observed due to the destruction of the system and accompanied by the release of thiolated PpIX, and the photodynamic activity after 2 h was higher than that of PpIX under the same conditions. Furthermore the system showed more efficient photodynamic antibacterial capacity under light exposure. Moreover, the pot experiment also verified that the system showed outstanding control efficacy against cabbage soft rot caused by Erwinia carotovora Sclerotinia. Safety test exhibited that the size of nanoparticles can restrict the entry of nanoparticles into the plant cells to trigger photocytotoxicity. The design strategy provides a platform for promoting the utilization of photoactivated pesticides and reducing or avoiding their harm to target plants and the environment.
研究领域:
植物学
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微生物学
·
农药科学
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DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2021
·
IF 5.875
Xuerong Dong,Xiang Zhang,Manyuan Wang,Liwei Gu,Jing Li,Muxin Gong
Heme is a prosthetic group of hemoglobin comprising protoporphyrin IX (PPIX) with Fe 2+ . Studies have shown that modulating heme synthesis pathway in Plasmodium could greatly affect the action mechanism and antimalarial effect of artemisinin and its derivatives. Herein, an intraerythrocytic parasite targeted nanostructured lipid carrier (NLC) was developed for potentiation of artemether (ARM) by combination with PPIX and iron-loaded transferrin (holo-Tf). Firstly, ARM and PPIX were co-loaded into NLCs with high entrapment efficiency. Then, a targeting ligand heparin (HP) was electrostatically adsorbed onto the periphery of NLCs, followed by conjugation with holo-Tf to receive the final formulation Tf-HP-NLC/ARM/PPIX. Tf-HP-NLC/ARM/PPIX exhibited nanoscale particle size (~188 nm) and was relatively stable in simulated gastrointestinal fluids and rat plasma. A sustained drug release characteristic was observed in PBS (pH 7.4). In vitro targeting assay confirmed that Tf-HP-NLC/ARM/PPIX could be specifically and efficiently internalized into intraerythrocytic parasites via HP receptor-meditated endocytosis. Furthermore, due to enhanced intraparasitic accumulation and activated mechanism of ARM, the combinational delivery system Tf-HP-NLC/ARM/PPIX showed increased inhibitory activity against Plasmodium falciparum in culture and enhanced antimalarial effect in Plasmodium berghei -infected murine model, suggesting a promising strategy for development of new therapy based on action mechanism of ARM.
研究领域:
药剂学
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寄生虫学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Yin Zhou,Yutong Chen,Wentao Zhao,Jiafeng Wang,Yi Chen,Haobo Wen,Yiyan He,Ning Li,Hongli Mao,Yuwen Cui,Zhongwei Gu
Intracellular bacterial infections are challenging due to immune evasion and antibiotic resistance, especially within macrophages harboring dormant bacteria. Here, a synergistic antibacterial strategy is presented using the PG3M@GaPP nanoflowers, which integrate immune modulation, iron metabolism disruption, and antibacterial photodynamic therapy (APDT) to eliminate intracellular bacteria. This nanoflower encapsulates a gallium–protoporphyrin IX complex (GaPP) within mannose-functionalized poly-l-lysine dendrimers (PG3M), enabling targeted delivery to macrophages via mannose receptor recognition. PG3M@GaPP promotes macrophage polarization to the anti-inflammatory M2 phenotype, enhancing immune modulation and bacterial uptake. The platform’s positive charge facilitates endosomal escape, releasing GaPP in the acidic intracellular environment, where free iron ions compete with gallium ions to form the iron–protoporphyrin IX complex (FePP). This disrupts the gallium/iron ion balance, enhancing the Trojan horse effect of gallium ions and inducing iron metabolism-dependent bacterial death. Additionally, laser activation of GaPP generates reactive oxygen species (ROS), further amplifying bacterial killing via APDT. In vitro and in vivo experiments show that PG3M@GaPP outperforms both free GaPP and commercial antibiotics in eliminating intracellular bacteria. These nanoflowers offers an alternative, nonantibiotic approach to combat intracellular infections, addressing drug resistance and providing a promising platform for antibacterial therapies.
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PubMed
高影响因子
Nanoscale Research Letters
·
2019
·Vol. 14
·期 1
·1-12
·
IF 3.159
Yu Yueming,Wang Bingjie,Guo Chunjing,Zhao Feng,Chen Daquan
Laminarin conjugate-based nano-scaled particles were in this study proposed as a delivery system for protoporphyrin IX (Pp IX) in photodynamic therapy (PDT) of human breast cancer cells (MCF-7). Hematin-Laminarin-Dithiodipropionic Acid-MGK, named as HLDM, was an amphiphilic carrier material with dual pH/redox sensitive that could be used to load hydrophobic drug to improve their solubility and enhance biocompatibility. Therefore, we combined photosensitizer (Pp IX) with HLDM to fabricate a novel nano-micelles, herein called Pp IX-loaded HLDM micelles. The Pp IX-loaded HLDM micelles were 149.3 ± 35 nm sized in neutral water. Phototoxicity, in vitro PDT effect, and dual sensibility to pH and redox microenvironment of Pp IX-loaded HLDM micelles were examined at different concentrations by using MCF-7 human breast cancer cells. The experiments on phototoxicity and reactive oxygen species (ROS) production proved that the micelles could produce PDT to kill the cancer cells with a certain wavelength light. The apoptosis experiment indicated that the micelles could cause nuclear damage. In vivo PDT effect of the micelles was studied by constructing the tumor-bearing nude mouse model of MCF-7 cells. In vivo studies showed that the Pp IX-loaded HLDM micelles could induce remarkable anti-tumor effect. A promising laminarin-based nanomedicine platform acts as a new drug delivery system to enhance the uptake, accumulation, and PDT efficacy of Pp IX in vitro and in vivo.
研究领域:
药学
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纳米技术
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肿瘤学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）