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BIOMATERIALS · 2021 · IF 12.479

An efficient photochemotherapy nanoplatform based on the endogenous biosynthesis of photosensitizer in macrophage-derived extracellular vesicles

Ruomeng Li,Xue Gong,Chen Hong,Hong Wang,Yingying Chen,Kaiyue Tan,Xiaoqing Liu,Fuan Wang

Extracellular vesicles (EVs) have been emerged as versatile drug delivery vehicles due to their outstanding biocompatibility and long-term circulation, yet are constrained with low targeting property and inefficient loading capacity from post-synthetic passive EVs encapsulation. Herein, we report a simple and feasible in situ biosynthetic approach to encapsulate tumor-targeting folate (FA)-modified EVs with intracellularly produced protoporphyrin X (PpIX) and doxorubicin (DOX). As compared with the traditional directly drug-incubated or drug-electroporated EVs, these biosynthesized EVs revealed high drug-loading efficiency with minimized structural and functional perturbations. Our multifunctional EVs revealed the enhanced accumulation and penetration into deep tumor parenchyma, as well as the strengthened immune response to ablate orthotopic and metastatic tumors, thus realizing the more reliable photochemotherapy. As an intelligent multi-mode therapeutic system, our biosynthetic EVs could be engineered with more therapeutic agents and show great promise for biomedicine applications.

研究领域: 生物医学工程 · 肿瘤学 · 药剂学
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TALANTA · 2025 · IF 6.1

Colorimetry/fluorescence dual-signal sensing system based on peptide nanotubes activating hemin and PPIX for sensitive detection of tannic acid

Rong Tang,Chenglin Zhang,Baolian Liu,Yujie Kang,Ya Wang,Xiupei Yang

Recently, it has become valuable to develop strategies based on multi-mode sensors to detect analytes related to human health, food safety and environmental pollution. In this study, KL@PPIX-hemin composite prepared by immobilizing hemin and protoporphyrin IX (PPIX) on self-assembled peptide nanotubes (PNTs) through multiple non-covalent interactions were used for colorimetric/fluorescent dual-mode sensing of tannic acid (TA). PNTs as a carrier can provide the hydrophobic microenvironment for hemin and PPIX to protect them from dimerization, thus activating their respective peroxidase-mimicking activity and fluorescence emission. Further experiments show that the composite could catalyze H 2 O 2 to oxidize colorless 3,3′,5,5′-tetramethylbenzidine (TMB) to generate blue ox-TMB, which could exactly quench the emission of PPIX by inner filter effect. The added TA can reduce ox-TMB to TMB and further turn on the fluorescence of system. A colorimetric/fluorescent dual-mode sensing system for TA was thus constructed and a low limit of detection (13.2 nM) was obtained. In addition, the analytical strategy has been successfully applied to accurate TA determination in actual tea samples. The method was also combined with smartphone to achieve visual detection of TA, which provides a broad prospect for portable and rapid tannic acid analysis.

研究领域: 分析化学 · 生物医学工程 · 食品安全检测
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JOURNAL OF CONTROLLED RELEASE · 2017 · IF 7.786

Plasma membrane activatable polymeric nanotheranostics with self-enhanced light-triggered photosensitizer cellular influx for photodynamic cancer therapy

Hao-Ran Jia,Yao-Wen Jiang,Ya-Xuan Zhu,Yan-Hong Li,Hong-Yin Wang,Xiaofeng Han,Zhi-Wu Yu,Ning Gu,Peidang Liu,Zhan Chen,Fu-Gen Wu

To address the issue of low cellular uptake of photosensitizers by cancer cells in photodynamic therapy (PDT), we designed a smart plasma membrane-activatable polymeric nanodrug by conjugating the photosensitizer protoporphyrin IX (PpIX) and polyethylene glycol (PEG) with glycol chitosan (GC). The as-prepared GC-PEG-PpIX can self-assemble into core-shell nanoparticles (NPs) in aqueous solution and the fluorescence of PpIX moieties in the inner core is highly quenched due to strong π – π stacking. Interestingly, when encountering plasma membranes, the GC-PEG-PpIX NPs can disassemble and stably attach to plasma membranes due to the membrane affinity of PpIX moieties, which effectively suppresses the self-quenching of PpIX, leading to significantly enhanced fluorescence and singlet oxygen ( 1 O 2 ) production upon laser irradiation. The massively produced 1 O 2 can compromise the integrity of the plasma membrane , enabling the influx of extracellular nanoagents into cells to promote cell death upon further laser irradiation. Through local injection, the membrane anchored GC-PEG-PpIX enables strong physical association with tumor cells and exhibits highly enhanced in vivo fluorescence at the tumor site. Besides, excellent tumor accumulation and prolonged tumor retention of GC-PEG-PpIX were realized after intravenous injection, which ensured its effective imaging-guided PDT.

CAS / MDL: 67-68-5 6066-82-6
研究领域: 生物医学工程 · 肿瘤学 · 纳米医学
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Food Bioscience · 2024 · IF 4.8

The pigment transformation from nitrosylheme to Zn-protoporphyrin IX in cooked ham products

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 · 微生物学
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JOURNAL OF APPLIED POLYMER SCIENCE · 2022 ·Vol. 140 ·期 7 ·e53485 · IF 3.057

Synthesis of water-soluble protoporphyrin IX polymers and their photodynamic application

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 · 材料科学 · 医学
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ACS Omega · 2021 · IF 3.512

Spectroscopic and Theoretical Investigation of β-Lactoglobulin Interactions with Hematoporphyrin and Protoporphyrin IX

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.

CAS / MDL: 7722-84-1 553-12-8
研究领域: 生物化学 · 药物递送 · 光动力治疗
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PHOTOCHEMISTRY AND PHOTOBIOLOGY · 2020 ·Vol. 96 ·期 5 ·1088-1095 · IF 2.721

Solubilization of Hexyl Aminolevulinate by Surfactants for Tumor Fluorescence Detection

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 .

CAS / MDL: 553-12-8
研究领域: 生物化学 · 医学 · 药理学
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ANALYTICAL SCIENCES · 2016 ·Vol. 32 ·期 8 ·887-892 · IF 1.174

A Label-free, Highly Sensitive and Selective Detection of Hemin Based on the Competition between Hemin and Protoporphyrin IX Binding to G-Quadruplexes

Kang Bei Hua,Li Na,Liu Shi Gang,Li Nian Bing,Luo Hong Qun

Herein is reported a simple and label-free fluorescent detection method for hemin based on using protoporphyrin IX (PPIX) as a fluorescent signal reporter. PPIX emits weak fluorescence in an aqueous solution. When PPIX binds to G-quadruplexes, the fluorescence intensity of PPIX is greatly increased. While in the presence of target hemin, hemin competes with PPIX toward G-quadruplexes because its affinity to G-quadruplexes is higher than that of PPIX. With the formation of the hemin-G-quadruplex complex, PPIX is released to the solution from the G-quadruplex accompanied by quenching of the fluorescence of the system. This fluorescence change of the system can be used to monitor hemin with a low detection limit of 36 nM. In addition, the possible binding sites for PPIX binding to the G-quadruplex are discussed based on competition between hemin and PPIX. What is more, this method might pave the way for applying G-quadruplexes and PPIX to more sensing systems.

CAS / MDL: 67-68-5 16009-13-5
研究领域: 分析化学 · 生物化学 · 分子生物学
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JOURNAL OF COLLOID AND INTERFACE SCIENCE · 2021 · IF 8.128

A heme-regulatable chemodynamic nanodrug harnessing transcription factor Bach1 against lung cancer metastasis

Yaxin Zhou,Qian Du,Qingyun Zhao,Mengzhu Zhang,Xiaohan Qin,Yue Jiang,Yuxia Luan

Non-small cell lung cancer (NSCLC) is a type of cancer dominated by metastasis-induced death. The transcription factor BTB and CNC homology 1 (Bach1) regulates almost all metastasis steps by activating the transcription of critical metastatic genes. It is urgent to engineer a nanodrug enabling regulation of Bach1 against tumor metastasis. Herein, a minimalist nanodrug integrating chemodynamic therapy (CDT) and Bach1 degradation was reported to prevent metastasis of NSCLC. The nanodrug was achieved by self-assembly of ferrocene (Fc) and Tin protoporphyrin IX (TinPPIX). In our nanodrug, Fc not only triggers the production of highly cytotoxic ∙OH for tumor ablation via Fenton reaction, but also induces heme release from heme-containing proteins to stimulate Bach 1 degradation. Moreover, TinPPIX further augments the free heme level along with amplifies the CDT efficacy by disabling heme oxygenase-1 (HO-1)-mediated heme conversion into antioxidative bilirubin . The results showed that, compared with control group, TinPPIX/Fc nanodrug caused a four-fold increase in heme level, which triggered remarkable Bach1 degradation in Fbxo22-mediated manner and successfully inhibited Bach1-dominated metastasis. Therefore, this nanodrug could powerfully impeded NSCLC progression and metastasis, offering an innovative heme-regulatable chemodynamic therapeutic approach for lung cancer with strong metastasis capability.

研究领域: 肿瘤学 · 分子生物学 · 纳米医学
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INTERNATIONAL JOURNAL OF PHARMACEUTICS · 2021 · IF 5.875

Heparin-decorated nanostructured lipid carriers of artemether-protoporphyrin IX-transferrin combination for therapy of malaria

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 · 寄生虫学 · 分子生物学
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EUROPEAN POLYMER JOURNAL · 2022 · IF 5.546

Bacteria-targeting photoactivated antibacterial nanosystem based on oligoalginate-protoporphyrin IX for plant disease treatment

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.

CAS / MDL: 73-22-3
研究领域: 植物学 · 微生物学 · 农药科学
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SPECTROSCOPY LETTERS · 2013 · IF 0.667

Determination of Protoporphyrin IX Disodium Salt Based on Fluorescence Quenching of Glutathione-Capped Cadmium/Tellurium Quantum Dots

Pingping Li,Jing Song,Yizhong Shen,Youqiu He

Aqueous glutathione-capped cadmium/tellurium quantum dots with a diameter of about 3 nm were synthesized. The fluorescence was quenched in the presence of protoporphyrin IX disodium salt, with the excitation wavelength at 320 nm. Under the optimal conditions, the quenched fluorescence intensity was linear in the range of 0.096–16 µg · mL−1 with a concentration of protoporphyrin IX disodium salt, and the detection limit (3σ) was 2.8 × 10−2 µg · mL−1. The proposed method has been applied to the determination of protoporphyrin in serum samples with satisfactory results. The interaction mechanism was investigated.

CAS / MDL: 70-18-8 50865-01-5
研究领域: 分析化学 · 生物医学
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