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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 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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CARBOHYDRATE POLYMERS · 2017 · IF 4.811

The effect of α-cyclodextrin on poly(pseudo)rotaxane nanoparticles self-assembled by protoporphyrin modified poly(ethylene glycol) for anticancer drug delivery

Taotao Xu,Junhua Li,Jun Cao,Wenxia Gao,Li Li,Bin He

Poly(pseudo)rotaxane (PPR) nanoparticles was facilely prepared using poly(ethylene glycol) (PEG) modified with protoporphyrin (PpIX) and α-cyclodextrin (α-CD) via host-guest interaction, the effect of α-CD number on the nanoparticle properties was investigated. The PEG with protoporphyrin (PEG-PpIX) end capping was synthesized via coupling reaction and the poly(pseudo)rotaxane nanoparticles with different amount of α-CD were fabricated by host-guest interaction between mPEG-PpIX and α-CDs. The final product was characterized by nuclear magnetic spectrum ( 1 H NMR), X-ray diffraction (XRD), atomic force microscope (AFM) and dynamic light scattering (DLS). The results showed that the poly(pseudo)rotaxane nanoparticles with uniform spherical shape was successfully prepared and doxorubicin (DOX) could be efficiently encapsulated in the nanoparticles. The amount of α-CDs in poly(pseudo)rotaxane nanoparticles was proportional to micellar size and drug release rate. The nanoparticles with higher α-CD number showed better anticancer efficacy in half maximal inhibitory concentration (IC 50 ) test. The cell internalization efficiency of DOX-loaded poly(pseudo)rotaxane nanoparticles could be further improved by lowering the α-CD number to receive smaller nanoparticle size.

CAS / MDL: 10016-20-3 553-12-8
研究领域: 生物化学 · 药学 · 材料科学
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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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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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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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ACS Sustainable Chemistry & Engineering · 2019 · IF 6.97

Enhanced Phototherapy Activity by Employing a Nanosilica-Coumarin–Acifluorfen Conjugate as the Supplementary Light Source Generator

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.

研究领域: 植物学 · 药理学 · 生物医学工程
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ACS Applied Materials & Interfaces · 2016 · IF 7.145

Real-Time Fluorescence Tracking of Protoporphyrin Incorporated Thermosensitive Hydrogel and Its Drug Release in Vivo

Xia Dong,Chang Wei,Tianjun Liu,Feng Lv,Zhiyong Qian

Fluorescence imaging in vivo will pave an important way for the evaluation of biomaterials. The major advantage of fluorescence imaging compared to other imaging modalities is the possibility of tracking two or more fluorescence probes simultaneously with multispectral fluorescence imaging. It is essential to elucidate the location, erosion, drug release and resection of implanted biomaterials in vivo. Herein, a thermosensitive hydrogel with a protoporphyrin core based on a PEG and PCL copolymer (PCL–PEG–PPOR–PEG–PCL) was synthesized by ring-opening polymerization using protoporphyrin as a fluorescence tag. The optical properties of the hydrogel were investigated by UV–vis and fluorescence spectroscopy in vitro and by fluorescence imaging system in vivo. The hydrogel erosion and drug delivery in vivo were monitored and tracked by multispectral fluorescence imaging system in nude mice. The results show that the thermosensitive hydrogel exhibits fluorescence and injectability in vivo with good biocompatibility. Through the modality of fluorescence imaging, the status of the hydrogel is reflected in situin vivo including its location and erosion. Multispectral analysis separates the autofluorescence signals from the specific label and provides the ability to locate the drug and carrier. The protoporphyrin incorporated thermosensitive hydrogel can be a potential visiable biomedical implant for tissue repair or drug delivery.

研究领域: 生物材料 · 医学影像 · 药理学
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF RAMAN SPECTROSCOPY · 2020 ·Vol. 51 ·期 12 ·2447-2457 · IF 2

Validation of the laser-induced fluorescence effect of aromatic amino acids, protoporphyrin IX, and tetracycline hydrochloride on hydroxyapatite

Kainan Zhang,Xinjie Cai,Yaru Guo,Chuanzi Liu,Tao Jiang,Yining Wang

Changes in mineral content (mainly phosphate) are important for detecting primary dental caries. However, so far, there has not been a device that can provide detailed information on the changes in organic and inorganic content of dental caries during the caries development and sensitively found early dental caries. DIAGNOdent has been widely used as a laser device for detecting dental caries, but it does not provide information about dental inorganics. Our experiment synthesised hydroxyapatite-aromatic amino acids (HA-AAAs), protoporphyrin IX (HA-PPIX), and tetracycline hydrochloride (HA-TCN) complexes as a simple biological mineralization model related to teeth in vitro and achieved single-factor control to avoid impurity interference so that the test results are accurate. For the first time, Raman and DIAGNOdent were used to detect HA-AAAs, HA-PPIX, and HA-TCN and determine the fluorescence characteristics of each organic substance. Our results show that Raman results are consistent with DIAGNOdent readings when detecting complexes and that Raman relative intensity (RRI) calculated by Raman spectroscopy can directly reflect the phosphate content in the sample. This implies that Raman is possible to replace DIAGNOdent as a novel and more accurate caries detector after conversion of the spectrum results.

CAS / MDL: 553-12-8 35943-35-2
研究领域: 牙科学 · 生物矿化 · 光学检测技术
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