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International Journal of Nanomedicine · 2024 · IF 6.6

Preparation of Hematoporphyrin-Poly(Lactic Acid) Nanoparticles Encapsulated Perfluoropentane/Salicylic Acid for Enhanced US/CEST MR Bimodal Imaging

Liqiong Ding,Fengnan Xu,Binhua Luo,Liyuan Cheng,Lingping Huang,Yanlong Jia,Jieqiong Ding

Background Medical imaging modalities, such as magnetic resonance imaging (MRI), ultrasound, and fluorescence imaging, have gained widespread acceptance in clinical practice for tumor diagnosis. Each imaging modality has its own unique principles, advantages, and limitations, thus necessitating a multimodal approach for a comprehensive disease understanding of the disease process. To enhance diagnostic precision, physicians frequently integrate data from multiple imaging modalities, driving research advancements in multimodal imaging technology research.Methods In this study, hematoporphyrin-poly (lactic acid) (HP-PLLA) polymer was prepared via ring-opening polymerization and thoroughly characterized using FT-IR, 1H-NMR, XRD, and TGA. HP-PLLA based nanoparticles encapsulating perfluoropentane (PFP) and salicylic acid were prepared via emulsion-solvent evaporation. Zeta potential and mean diameter were assessed using DLS and TEM. Biocompatibility was evaluated via cell migration, hemolysis, and cytotoxicity assays. Ultrasonic imaging was performed with a dedicated apparatus, while CEST MRI was conducted using a 7.0 T animal scanner.Results We designed and prepared a novel dual-mode nanoimaging probe SA/PFP@HP-PLLA NPs. PFP enhanced US imaging, while salicylic acid bolstered CEST imaging. With an average size of 74.43 ± 1.12 nm, a polydispersity index of 0.175 ± 0.015, and a surface zeta potential of −64.1 ± 2.11 mV. These NPs exhibit excellent biocompatibility and stability. Both in vitro and in vivo experiments confirmed the SA/PFP@HP-PLLA NP’s ability to improve tumor characterization and diagnostic precision.Conclusion The SA/PFP@HP-PLLA NPs demonstrate promising dual-modality imaging capabilities, indicating their potential for preclinical and clinical use as a contrast agent.

CAS / MDL: 7722-84-1 301-10-0
研究领域: 医学影像学 · 纳米医学 · 生物材料学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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MYCOSES · 2020 ·Vol. 63 ·期 11 ·1215-1225 · IF 3.575

Evaluation of the photodynamic efficacy and effects of haematoporphyrin monomethyl ether on Trichophyton rubrum microconidia in vitro

Tiantian Pan,Xiaojing Liu,Chengcheng Liu,Jiao Li,Wenpeng Ma,Yannan Qin,Yunru Chen,Shumei Lin,Feng Ye

Background Current available treatment modes against dermatophytoses are often tedious and sometimes unsatisfactory. As an emerging and promising approach, antimicrobial photodynamic therapy (aPDT) attracts much attention in the treatment of superficial or localised infections. Objectives This work investigated the photodynamic efficacy and effects of haematoporphyrin monomethyl ether (HMME) on microconidia of Trichophyton rubrum in vitro. Methods The photodynamic killing efficacy of HMME on microconidia of two T rubrum strains was assessed by MTT assay. The effects of HMME-mediated aPDT on the growth of T rubrum and cellular structure of microconidia were also investigated. Confocal laser scanning microscopy (CLSM) and flow cytometry were employed to study the intracellular localisation of HMME and generation of reactive oxygen species (ROS). Results HMME showed no obvious toxicity in the dark, but after light irradiation it inactivated the T rubrum microconidia in a light energy dose-dependent manner, and inhibited the growth of T rubrum . CLSM demonstrated that HMME initially bound to the cell envelop and entered into the cell after light irradiation. HMME-mediated aPDT also damaged the cell cytoplasm and increased the accumulation of intracellular ROS, resulting in cell death. Conclusions The results suggested that HMME-mediated aPDT had potential to be used in the treatment of superficial infections caused by T rubrum .

研究领域: 医学 · 微生物学
✓ 已验证 DOI PubMed 高影响因子
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EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES · 2021 · IF 4.384

Co-delivery of gefitinib and hematoporphyrin by aptamer-modified fluorinated dendrimer for hypoxia alleviation and enhanced synergistic chemo-photodynamic therapy of NSCLC

Fangyin Zhu,Liang Xu,Xudong Li,Ziying Li,Jun Wang,Haijun Chen,Xiumei Li,Yu Gao

Although epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs)-based molecular targeted therapy are proved to be effective in the treatment of non-small cell lung cancer (NSCLC) with EGFR mutation, its efficacy is limited by the acquired drug resistance. The combination of EGFR-TKIs with photodynamic therapy (PDT) has been explored to combat NSCLC with promising synergistic results. However, hypoxic tumor microenvironment is associated with the development of EGFR-TKIs resistance and severely limits the efficacy of PDT. Here, we synthesized an aptamer modified fluorinated dendrimer (APF) as a drug carrier and prepared nanocomplexes APFHG by encapsulation of gefitinib (Gef) and hematoporphyrin (Hp). APF has good oxygen-carrying capacity, high drug entrapment efficiency, and could release Gef and Hp in response to intracellular pH. APF can specifically recognize EGFR-positive NSCLC cells and effectively improve the tumor hypoxic microenvironment due to the targeting effect of aptamer and the good oxygen-carrying capacity of the fluorinated dendrimer. Under the laser irradiation, APFHG can significantly increase the production of the intracellular reactive oxygen species and produce a synergistic therapeutic effect in inhibition of cellular growth and induction of cell cycle arrest and apoptosis on both Gef-sensitive and Gef-resistant EGFR-mutant NSCLC cells through PDT/molecular targeted therapy. This work indicates that fluorinated dendrimer could be a potent drug delivery platform to overcome hypoxia-related resistance and the co-delivery of EGFR-TKI and photosensitizer by the fluorinated dendrimer could be a promising therapeutic approach for reversal of EGFR-TKIs resistance in EGFR mutation-positive NSCLC.

研究领域: 肿瘤学 · 药剂学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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DYES AND PIGMENTS · 2018 · IF 3.767

A hematoporphyrin and indocyanine green co-delivery system with NIR triggered-controllable photoactivities for photodynamic therapy

Ziying Li,Tingting Lv,Yingying Zhang,Liang Xu,Lu Zhang,Xiuying Wang,Haijun Chen,Yu Gao

Photodynamic therapy (PDT) was hindered by the poor water solubility and long-enduring photoactivities of photosensitizers . Here, we developed a novel controllable photodynamic agent CPHI based on β-cyclodextrin modified polyamidoamine (PAMAM) dendrimer (CP) co-delivery of indocyanine green (ICG) and hematoporphyrin (HP). The CPHI possessed appropriate particle sizes and zeta potentials , considerable photostability, and NIR-triggered release property. The fluorescence of HP could be quenched by ICG when HP and ICG were co-loaded inside the CP, and the quenching efficiency was related with the weight ratio of HP and ICG. When the feeding weight proportion of HP and ICG is 1/10, the fluorescence of HP was quenched by 87.3% in CPHI. Under 808 nm laser irradiation , the ICG in CP was degraded, and the fluorescence of HP could recover. The recovered HP was capable of generating reactive oxygen species (ROS) for PDT with 606 nm laser irradiation. The cytotoxicity and cell apoptosis studies showed that CPHI could effectively induce MCF-7 cells apoptosis with PDT effects under 808/660 nm laser. These results suggested that CPHI could be an efficient cancer therapeutic agent for controllable PDT with low dark toxicity.

CAS / MDL: 111689-03-3
研究领域: 医学 · 生物材料学
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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
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Journal of Materials Chemistry B · 2023 ·Vol. 11 ·期 25 ·5910-5921 · IF 7

A pectin-based photoactivated bactericide nanosystem for achieving an improved utilization rate, photostability and targeted delivery of hematoporphyrin

Yun Li,Zhi Cai,Yihua Yin,Ying Yi,Weiquan Cai,Shengxiang Tao,Mengting Du,Jingli Zhang,Ruyu Cao,Yijing Luo,Wenjin Xu

Photoactivated pesticides have many advantages, such as high activity, low toxicity, and no drug resistance. However, poor photostability and a low utilization rate limit their practical application. Herein, the photosensitizer hematoporphyrin (HP) was used as a photoactivated pesticide, covalently linked with pectin (PEC) via ester bonds, to prepare an amphiphilic polymer pro-bactericide, and subsequently self-assembled in aqueous solutions to obtain an esterase-triggered nanobactericide delivery system. The fluorescence quenching effect due to the aggregation of HP in nanoparticles (NPs) enabled the inhibition of photodegradation of HP in this system. Esterase stimulation could trigger HP release and increase its photodynamic activity. Antibacterial assays have shown that the NPs had potent antibacterial capacity, almost completely inactivating bacteria after 60 min of exposure to light. The NPs had good adherence to the leaves. Safety assessment indicated that the NPs have no obvious toxic effects on plants. Antibacterial studies on plants have shown that the NPs have excellent antibacterial effects on infected plants. These results provide a new strategy for obtaining a photoactivated bactericide nanosystem with a high utilization rate and good photostability and targeting ability.

CAS / MDL: 307554-62-7 9005-65-6
研究领域: 农药科学 · 植物保护 · 生物化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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DYES AND PIGMENTS · 2019 · IF 4.018

Water-soluble sulfonate porphyrin functionalized hyaluronic acid with comb-like structure: Potential photosensitizers for photodynamic therapy

Xu Cui,Yanhui Li,Yanwei Li,Baoguo Qiu,Qian Duan

A water-soluble comb-like porphyrin polymer based on hyaluronic acid ( HA ) as the main chain and sulfonate substituted tetraphenylporphyrin ( TASP ) as side groups, named as HA- g -NH-TPP-(SO 3 Na) [( HA- g -TASP )], was designed and synthesized, which could be used as a potential photosensitizer in photodynamic therapy (PDT). This photosensitizer displayed high-water solubility, low dark cytotoxicity, high photocytoxiticy and high singlet oxygen yield ( Φ Δ  = 0.86). The HA- g -TASP was carefully characterized by UV–Vis, FTIR, and 1 H NMR. UV–Vis spectra showed the Q bands of the HA- g -TASP spectrum had a significant red shift about 50 nm to near-infrared (NIR) region compared with TASP , the HA- g -TASP had a smaller energy band gap . The NIR region is known as the transparent window of the organisms, NIR irradiation shows larger penetration distance in tissue. As a novel photosensitizer, HA- g -TASP exhibited low cytotoxicity in dark and also low photocytotoxicity towards normal cells, but performed enhanced photodynamic activity against cancer cells (HeLa cells). As a result, HA- g -TASP with comb-like structure may be a useful photosensitizer for practical photodynamic therapy in the future.

研究领域: 生物化学 · 药物化学 · 肿瘤学
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EUROPEAN POLYMER JOURNAL · 2023 · IF 6

Bacteria-triggered photodynamic nano-system based on hematoporphyrin-modified chitosan for sustainable plant disease control

Mengting Du,Ying Yi,Yihua Yin,Zhi Cai,Weiquan Cai,Junli Li,Guanghua He,Jingli Zhang

Faced with increasingly serious drug resistance and environmental pollution, there is an urgent necessity to develop green and efficient pesticides with new mechanisms of action. A novel antibacterial nano-system for plant protection based on photodynamic action was prepared by grafting hematoporphyrin (HP) onto modified chitosan through ester bonding. The self-quenching effect caused by aggregation of grafted HP could effectively inhibit its photodegradation, thus enhancing its photostability. The breakage of ester bonds induced by enzyme stimulation at the sites of bacterial infection could trigger HP release exerting an efficient photodynamic effect. The antibacterial experiments showed that the nanoparticles (NPs) have good photodynamic antibacterial activity, and the inhibition rate was as high as 96 % after 60 min of light exposure. Adhesion and safety studies have shown that the NPs are well retained on plant foliage without causing damage to the crop. Thus, NPs have great potential in sustainable plant disease management.

研究领域: 农业科学 · 生物技术 · 环境科学
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INORGANIC CHEMISTRY · 2022 · IF 5.436

Intrinsic Characterization Method on the Heavy Atom Effect of Metalloporphyrins

Meng Kou,Feng Qin,Yongda Wang,Xiyu Zhang,Hua Zhao,Ye Tian,Zhiguo Zhang

The presence of room temperature phosphorescence emission in metalloporphyrin, via the transition from the excited triplet state (T1) to the ground state (S0), relies on the chelated heavy metal ions, which is known as the heavy atom effect (HAE). Despite the HAE being a reliable method to tune the phosphorescence process widely, the realization of the HAE nature is a tough task as the induced phosphorescence process is sensitive to not only the specie of bonded heavy atoms but also chemical environments such as the oxygen quenching and solvent effect. In this study, we have aimed at a quantitative determination of the intrinsic phosphorescent transition rate (kP) in metalloporphyrin gadolinium-labeled hematoporphyrin monomethyl ether (Gd-HMME). After the theoretical analysis based on the rate equation model to remove the nonintrinsic contribution and the experimental results of phosphorescence, the kP is calculated to be ∼2.4 × 10–4 μs–1. This study enables us to approach the intrinsic energy characteristic of metalloporphyrins; moreover, our work provides an effective pathway for the further optimization of the varied functional metalloporphyrin.

研究领域: 化学 · 材料科学 · 生物医学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF PHYSICAL CHEMISTRY B · 2023 · IF 3.3

Insight into the Heavy Atom Effect Induced by Environmental Heavy Atoms for Gadolinium-Labeled Hematoporphyrin Monomethyl Ether

Meng Kou,Feng Qin,Yongda Wang,Xiyu Zhang,Zheng Hu,Zhiguo Zhang

Environmental heavy atoms can further enhance the room temperature phosphorescence (RTP) emissions of gadolinium-labeled hematoporphyrin monomethyl ether (Gd-HMME) by way of the external heavy atom effect (HAE). However, the macroscopic phosphorescence intensity covered the intrinsic effect of the environmental heavy atoms. In this study, a method of separating the external HAE from the total is performed, and a quantity to describe the intrinsic nature of external HAE is defined. The environmental Gd3+ concentration evolution of the phosphorescent transition rate (kP) is obtained by correlated absorption, emission, and time-resolved spectroscopy. The kP increases linearly with environmental Gd3+ concentration, while the intercept kP0 coincides with that of the internal HAE. The slope κ could be calculated, and it is a quantity free of the Gd3+ concentration and only relies on the type of environmental heavy atoms. In addition, the environmental Lu3+ exhibits similar functionality to Gd3+ in external HAE. Environmental Pd2+ quenches the phosphorescence intensity macroscopically, while it enhances the HAE intrinsically. Our method provides an alternative insight into the intrinsic nature of environmental heavy atoms.

研究领域: 化学 · 生物医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Polymers · 2025 ·Vol. 17 ·期 9 ·1238 · IF 4.9

Novel Molecular Weight Gradient Hyaluronate Dissolving Microneedles for Sustained Intralesional Delivery and Photodynamic Activation of Hematoporphyrin in Port-Wine Stain Therapy

Xueli Peng,Chenxin Yan,Nengquan Fan,Chaoguo Sun,Suohui Zhang,Yunhua Gao

Port-wine stain (PWS), a progressive congenital vascular malformation characterized by ectatic dermal capillaries, demonstrates age-dependent lesion expansion and chromatic intensification, resulting in significant psychosocial comorbidity. While systemic hematoporphyrin (HP) administration remains the clinical paradigm for photodynamic therapy (PDT), its therapeutic utility is severely constrained by non-targeted biodistribution. Pharmacokinetic analyses reveal prolonged dermal retention and suboptimal lesion accumulation, predisposing 42% of patients to phototoxic reactions. To address these limitations, this work creatively suggested a local targeted drug delivery method based on soluble microneedles in response to the difficulties mentioned above. The rational design of a molecular weight (MW) HA gradient system enabled the engineering of ternary nanocomposite microneedles with enhanced biomechanical integrity (0.49 N/needle) and superior HP loading capacity, which collectively facilitated spatiotemporally controlled transdermal delivery of hematoporphyrin with complete dissolution within 30 min. The release performance, skin permeability, and storage stability of hematoporphyrin dissolving microneedles (HP-DMNs) have all been demonstrated in vitro. This study applies soluble microneedle technology to the delivery of HP in PWS for the first time. It avoids the risk of systemic exposure through precise local administration. It uses the rapid dissolution properties of microneedles to achieve high concentration and rapid release of drugs in skin lesions. This study provides a new strategy for sustained intralesional release and rapid drug delivery treatment of PWS and provides novel ideas for the development of new formulations of HP and related photosensitizers.

研究领域: 药剂学 · 医学工程 · 皮肤科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Nanoscale · 2021 ·Vol. 13 ·期 27 ·11953-11962 · IF 7.79

Nanoengineering of a newly designed chlorin e6 derivative for amplified photodynamic therapy via regulating lactate metabolism

Xiaohan Qin,Mengzhu Zhang,Xu Hu,Qian Du,Zhipeng Zhao,Yue Jiang,Yuxia Luan

Chlorin e6 (Ce6) is a widely utilized photosensitizer in photodynamic therapy (PDT) against tumor growth, but its hydrophobic feature and the hypoxia in the tumor microenvironment greatly compromise its therapeutic efficacy. To address the issues, here we designed a new Ce6 derivative (TCe6) by coupling Ce6 with amphiphilic D-α-tocopherol polyethylene glycol 1000 succinate (TPGS), endowing Ce6 with an excellent amphiphilic feature. In particular, the overall reactive oxygen species (ROS) generation by TCe6 was significantly enhanced because TPGS could interact with mitochondrial complex II to induce extra ROS production, amplifying the total ROS production under PDT. Inspired by the unique property of α-cyano-4-hydroxycinnamate (CHC) in regulating lactate metabolism to spare more intracellular oxygen for PDT, TCe6 was further co-assembled with CHC to construct TCe6/CHC nanoparticles (NPs) for addressing the insufficient oxygen issue in PDT. The as-prepared TCe6/CHC NPs not only increased the efficiency of cell internalization but also improved the solubility and stability of Ce6 and CHC. Thanks to the extra ROS production by the TPGS unit, the amphiphilic feature of TCe6 and the CHC-mediated hypoxia microenvironment, the TCe6/CHC NPs demonstrated excellent PDT against tumor growth. This work provided a versatile strategy to solve the current bottleneck in photosensitizer-based PDT, holding great promise for the design of advanced photodynamic nanoplatforms.

研究领域: 纳米技术 · 药学 · 肿瘤学
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