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MOLECULES · 2023 ·Vol. 28 ·期 12 ·4639 · IF 4.6

Monomer and Oligomer Transition of Zinc Phthalocyanine Is Key for Photobleaching in Photodynamic Therapy

Dafeng Liu,Longguang Jiang,Jincan Chen,Zhuo Chen,Cai Yuan,Donghai Lin,Mingdong Huang

Photodynamic therapy (PDT) is recognized as a powerful method to inactivate cells. However, the photosensitizer (PS), a key component of PDT, has suffered from undesired photobleaching. Photobleaching reduces reactive oxygen species (ROS) yields, leading to the compromise of and even the loss of the photodynamic effect of the PS. Therefore, much effort has been devoted to minimizing photobleaching in order to ensure that there is no loss of photodynamic efficacy. Here, we report that a type of PS aggregate showed neither photobleaching nor photodynamic action. Upon direct contact with bacteria, the PS aggregate was found to fall apart into PS monomers and thus possessed photodynamic inactivation against bacteria. Interestingly, the disassembly of the bound PS aggregate in the presence of bacteria was intensified by illumination, generating more PS monomers and leading to an enhanced antibacterial photodynamic effect. This demonstrated that on a bacterial surface, the PS aggregate photo-inactivated bacteria via PS monomer during irradiation, where the photodynamic efficiency was retained without photobleaching. Further mechanistic studies showed that PS monomers disrupted bacterial membranes and affected the expression of genes related to cell wall synthesis, bacterial membrane integrity, and oxidative stress. The results obtained here are applicable to other types of PSs in PDT.Keywords:photosensitizer (PS);photobleaching;photosensitizer aggregate;photosensitizer monomer

研究领域: 化学 · 生物医学工程 · 微生物学 · 分子生物学
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF CONTROLLED RELEASE · 2025 · IF 11.5

Red blood cell membrane-derived phototherapeutic nanodiscs: A new platform for enhanced phototherapy

Zhuge Deli,Li Li,Sun Xueying,Liang Hui,Jin Chenjie,Lu Ailing,Gao Wenli,Zhong Yutong,Li Wenlu,Chen Sihao,Wang Fang,Yan Linzhi,Meng Weiyang,Lin Xiaoji,Zhang Xufei,Liu Yong,Li Yuanfeng,Zhao Yingzheng,Zhang Xiang,Chen Mengchun,Chen Yijie

Phototherapy holds great potential for treating cancer and infections but faces limitations related to photosensitizer accumulation, tissue penetration, and diminished photo-conversion efficiency, particularly in deep-seated tumors and infections. Here, a biomimetic phototherapeutic nanodisc platform consisting of erythrocyte membranes and the photosensitizer IR780 is developed. With the advantages of the ultra-small size and exceptional biosafety of cell membrane-derived nanodiscs, this platform facilitates efficient accumulation and deep tissue penetration at disease sites. Upon near-infrared (NIR) irradiation, IR780 delivered via the nanodisc exhibits enhanced photothermal conversion efficiency, markedly inhibiting tumor growth in an orthotopic 4T1 breast cancer model and reducing bacterial load in a methicillin-resistant Staphylococcus aureus (MRSA) skin infection model. Furthermore, the nanodisc platform demonstrates outstanding biocompatibility in mice. In conclusion, this nanodisc system significantly extends the functional potential of cellular nanodiscs, presenting a promising strategy to address the challenges of photosensitizer delivery and biosafety in phototherapeutic applications.

CAS / MDL: 64-19-7 67-56-1 67-68-5
研究领域: 生物医学工程 · 肿瘤学 · 微生物学 · 材料科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CHEMICAL ENGINEERING JOURNAL · 2023 · IF 15.1

NIR-AIEgens nanospheres featuring high-fidelity dynamic lipid droplet targeting, expediting ferroptosis to annihilating tumor in hypoxia

Ke Xue,Yongfei Zhao,Saidong Sun,Yuanhang Li,Jiankang Liang,Zhengjian Qi

Severe ferroptosis is a non-apoptotic iron-dependent cell death pathway, and extreme hypoxia and anomalous iron metabolism in tumors critically suppress the efficacy of ferroptosis therapy. Overcoming tumor hypoxia while facilitating ferroptosis is an extremely challenging task. Herein, the photosensitizer named BOTTQ with specific targeting of lipid droplet (LD) was synthesized by increasing the tail chain length of triphenylamine. The addition of alkoxy chains optimized the molecular structure and fostered inter-system crossing and type I reactive oxygen species (ROS) generation. Besides, BOTTQ yielded large amounts of type I ROS under light excitation oxidize efficiently polyunsaturated fatty acids in lipid monolayer of LD and contribute to the formation of ferroptosis substrate. Meanwhile, the generation of type I ROS accelerated the Fenton reaction, thus effectively boosting the occurrences of ferroptosis. Furthermore, the successful encapsulation of BOTTQ into DSPE-PEG-MAL material not only elevates the stable type of nanoparticle colloids, but the MAL moiety can deplete the functional thiols of glutathione in a mild environment, which leads to glutathione failure and facilitates ferroptosis. Thus tumor-specific ferroptosis-inducing strategy offers a universally applicable therapy with the capacity to enhance type I ROS production and effectively contain tumorigenesis.

研究领域: 生物医学工程 · 肿瘤学 · 药理学
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DYES AND PIGMENTS · 2022 · IF 5.122

Mitochondria targeted upconversion molecular platform for photodynamic therapy of cancer cells

Yuanyuan Zhang,Jing Wang,Wanlu Sun,Hui Yu,Shubo An,Hai-Yan Wang,Yi Liu

Increasing interest has been noted in photosensitizer design. Currently, most small molecular photosensitizers have several drawbacks, including limited penetration depth and unsatisfying photostability. For addressing these limitations, Frequency upconversion luminescence (FUCL) small molecule was adopted as a photosensitizer design strategy for its deeper penetration, sensitive imaging, and better photostability. We developed a series of FUCL (NIR-NH 2 , NIR-NHEt, NIR-NEt 2 ) molecules with rigid structures. Equipped with the most powerful electron donor , NIR-NEt 2 exhibits the highest singlet oxygen generation, the strongest upconversion luminescence intensity under 808 nm irradiation and mitochondria-targeted ability. FUCL can be a superior molecular platform for image-guided photodynamic therapy of cancer cells.

CAS / MDL: 5471-63-6 298-93-1
研究领域: 化学 · 肿瘤学 · 分子生物学
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ACS Omega · 2023 · IF 4.1

Lutein-Based pH and Photo Dual-Responsive Novel Liposomes Coated with Ce6 and PTX for Tumor Therapy

Hong Shen,Changwei Zhang,Chengzhang Wang,Jianxin Jiang,Fengxia Tang,Chuan Li,Hua Yuan,Xiaoran Yang,Zhenkai Tong,Yi Huang

Liposomes are considered the best nanocarrier for delivering cancer drugs such as chlorin e6 (Ce6) and paclitaxel (PTX). However, the poor stability and non-selectivity release of liposomes may severely limit their further applications. In this study, based on the characteristics of lutein (L) photo-response and orthoester (OE) acid-response, stable and dual-responsive liposomes (Dr-lips) have been prepared. The Dr-lips exhibited a spherical shape with a uniform size of approximately 58.27 nm. Moreover, they displayed a zeta potential ranging from −45.45 to −28.25 mV and showed excellent storage stability, indicating stable colloidal properties. Additionally, they achieved high drug encapsulation rates, with 92.27% for PTX and 90.34% for Ce6, respectively. Meanwhile, under near-infrared (NIR) light at 660 nm, Ce6 plays a key role in accelerating the photodegradation rate of lutein and PEG-OE-L while also enhancing tissue penetration ability. Additionally, Dr-lips loaded with Ce6 and PTX not only displayed excellent pH and photo dual-responsiveness for targeted delivering and releasing but also showed remarkable reactive oxygen species (ROS) generation capacity and impressive anti-tumor activity in vitro. Therefore, it provides a novel strategy for optimizing stability and enhancing their targeted drug delivery of liposome.

研究领域: 药剂学 · 肿瘤学 · 生物医学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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MATERIALS SCIENCE FORUM · 2020 · IF 0

Synthesis of pH-Responsive Glycopolymer with End Group Zinc(II) Phthalocyanines as Potential Photosensitizer

Shu Guo Dong,Gui Hua Cui,Qian Duan

A novel end-functionalized glycopolymer poly (3-O-methacryloyl-D-glucofuranose) -b-poly (2-Diethylaminoethyl Methacrylate) (PMAGlc-b-PDEA-ZnTAPc) with zinc (II) teraamaninophthalocyanine was synthesized. First, a pH-responsive copolymer PMAIpG-b-PDEA was synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. Then PMAIpG-b-PDEA reacted with ZnTAPc and deprotected to form a water-soluble and pH-responsive photosensitizer. The structure of the PMAGlc-b-PDEA-ZnTAPc was characterized by 1H NMR and GPC. The photophysical properties were evaluated by UV-Vis and fluorescence spectra. The PMAGlc-b-PDEA-ZnTAPc can generate singlet oxygen species with good singlet oxygen quantum yields (Φ△=0.38), which is believed to be the major cytotoxic reactive oxygen species (ROS) for photodynamic therapy. The ZnPc functionalized glycopolymer will be used as a potential photosensitizer in the fields of photodynamic therapy.

研究领域: 材料科学 · 生物医学工程 · 药物化学
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ANALYTICAL CHEMISTRY · 2020 · IF 6.785

In Situ Monitoring of Mitochondria Regulating Cell Viability by the RNA-Specific Fluorescent Photosensitizer

Xiaojiao Zhu,Gang Liu,Yingcui Bu,Jie Zhang,Lianke Wang,Yupeng Tian,Jianhua Yu,Zhichao Wu,Hongping Zhou

Cell viability is greatly affected by external stimulus eliciting correlated dynamical physiological processes for cells to choose survival or death. A few fluorescent probes have been designed to detect whether the cell is in survival state or apoptotic state, but monitoring the regulation process of the cell undergoing survival to death remains a long-standing challenge. Herein, we highlight the in situ monitor of mitochondria regulating the cell viability by the RNA-specific fluorescent photosensitizer L. At normal conditions, L anchored mitochondria and interacted with mito-RNA to light up the mitochondria with red fluorescence. With external light stimulus, L generated reactive oxide species (ROS) and cause damage to mitochondria, which activated mitochondrial autophagy to prevent death, during which the red fluorescence of L witnessed dynamical distribution in accordance with the evolution of vacuole structures containing damaged mitochondria into autophagosomes. However, with ROS continuously increasing, the mitochondrial apoptosis was eventually commenced and L with red fluorescent was gradually accumulated in the nucleoli, indicating the programmed cell death. This work demonstrated how the delicate balance between survival and death are regulated by mitochondria.

研究领域: 细胞生物学 · 分子生物学 · 生物医学工程
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF FOOD SCIENCE · 2025 ·Vol. 90 ·期 3 ·e70167 · IF 3.4

Utilizing onion peel extract as photosensitizer combined with 405 nm blue light to control Salmonella Typhimurium on eggshells

Chae-Yeon Woo,Gi-Hyeok Lee,Kyung-Jik Lim,Jun-Won Kang

The use of blue light within a range of 400–470 nm holds significant potential for sanitization purposes. However, due to an extended exposure duration needed for an antibacterial effect, the utilization of a photosensitizer (PS) to increase the efficacy of the treatment becomes essential. This study investigated prospective use of onion peel extract as a PS in combination with 405 nm blue light for the inactivation of Salmonella Typhimurium, a common foodborne pathogen on eggs. Extracts were obtained using 99% ethanol, 50% ethanol, and distilled water (DW). Their photosensitizing activities were then compared. The combination of 405 nm blue light and onion peel extract using 99% ethanol reduced bacterial populations more effectively than blue light treatment alone, while also increasing reactive oxygen species generation, cell membrane permeability, lipid peroxidation, and DNA damage levels. However, the antimicrobial effect of the 99% ethanol extract did not show a concentration dependence. Spraying DW extract on eggshell treated with 99% ethanol onion peel extract at 1 mg/mL and blue light further enhanced Salmonella reduction. Liquid chromatography was conducted for component separation. However, none of the separated fractions exhibited a significant antibacterial effect, suggesting that the active compounds responsible for antibacterial activity might work synergistically in the crude extract rather than individually. In contrast, the crude extract exhibited a significant antibacterial effect, suggesting that 99% ethanol-extracted onion peel can serve as a PS, particularly in its crude state without purification, and effectively inactivate Salmonella on eggshells. Practical Application Antimicrobial blue light (aBL) in the range of 400–470 nm is a promising nonthermal technology with several advantages, including minimal impact on food quality and safety. This study optimized the concentration of onion peel extract to improve its effectiveness as a photosensitizer in aBL treatment against Salmonella Typhimurium on eggshells. These results may serve as a reference for further optimizing aBL treatments, offering a potentially sustainable and cost-effective photosensitizer for pathogen control.

CAS / MDL: 110231-30-6
研究领域: 食品安全 · 微生物学 · 食品科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Biomaterials Science · 2019 ·Vol. 8 ·期 3 ·830-836 · IF 5.251

A water soluble carbazolyl-BODIPY photosensitizer with an orthogonal D–A structure for photodynamic therapy in living cells and zebrafish

Chengjun Wang,Ying Qian

A novel photosensitizer carbazolyl-BODIPY (Cz-BODIPY) with an orthogonal donor–acceptor structure was developed for photodynamic therapy (PDT). The photosensitizer Cz-BODIPY showed strong singlet oxygen sensitizing capability (ΦΔ = 0.68 in MeOH), excellent water solubility in dilute solution, and high photostability. The photosensitizer Cz-BODIPY exhibited negligible dark cytotoxicity and high phototoxicity (IC50 0.45 μM). Cz-BODIPY could induce cell apoptosis upon light illumination. Three cell states including living cells, apoptotic cells, and dead cells in the PDT process of Cz-BODIPY were determined via the Hoechst 33342/PI dual staining assays. The ROS (reactive oxygen species) generation in living cells during the PDT process of Cz-BODIPY was captured by the ROS detector, dihydroethidium (DHE). The photosensitizer Cz-BODIPY could be assimilated by zebrafish to generate ROS and diminish the integrity of zebrafish tissue upon light illumination. Tumor cell growth could be inhibited by Cz-BODIPY upon light illumination. The photosensitizer Cz-BODIPY displayed potential in real PDT application.

研究领域: 生物化学 · 药理学 · 肿瘤学
✓ 已验证 DOI 高影响因子
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BIOORGANIC CHEMISTRY · 2025 · IF 4.7

A mono-substituted aluminum phthalocyanine photosensitizer with high phototoxicity index for effective bladder cancer treatment

Kebin Ye,Xinlu Bao,Zhikang Song,Mingzhu Zhang,Shaohua Wei,Jishuang Zhang,Lin Zhou

Photosensitizers are central to the efficacy of photodynamic therapy (PDT) in cancer treatment. The phototoxic index (PI) defines the therapeutic window of a photosensitizer, with the clinically used Photosens® exhibiting a PI of 725. In our study, we observed that Zn(II) phthalocyanine mono-β-substituted with 4-carboxyphenoxy (ZnPc-COOH) displayed a phototoxic IC 50 in bladder cancer T24 cells at approximately 11.2 nM, yet its dark toxicity was notably high, yielding a PI of only 199. We hypothesize that the elevated dark toxicity is linked to mitochondrial localization. Rather than employing traditional side-chain substitution strategies to mitigate dark toxicity, we adopted a center metal substitution approach, synthesizing the first Al(III) phthalocyanine mono-β-substituted with 4-carboxyphenoxy photosensitizer (AlPc-COOH). Remarkably, AlPc-COOH localized to the lysosome, exhibited a phototoxic IC 50 of 1 nM, and showed a nearly 89-fold reduction in dark toxicity, achieving a PI of 223,700, which is 1000 times greater than ZnPc-COOH. In a murine orthotopic bladder cancer model, AlPc-COOH demonstrated therapeutic efficacy comparable to that of the clinically used chemotherapeutic agent mitomycin C (MMC). This study provides a crucial foundation for the design of optimized mono-substituted aluminum phthalocyanine-based photosensitizers.

研究领域: 生物学 · 医学 · 药理学 · 肿瘤学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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POLYMER · 2024 · IF 4.1

A strategy for improving self-healing efficiency: Application of sensitizer in thymine photoresponsive materials

Bin Pu,Gaolang Xiao,Juying Xiao,Hua-Bing Yin,Jin Wang

Self-healing materials based on photodimerization have advantages such as being fast, efficient, environmentally friendly and controllable. However, most of photoresponsive self-healing materials suffer from a problem that there is a compromise between the strength and the self-healing efficiency. Therefore, most of the research focuses on using flexible materials to reach high self-healing efficiency. The absorption wavelengths of some photosensitive groups are narrow, which limits the application fields of self-healing properties of self-repairing materials. Here, we use photodimerizable thymine as the photoresponsive group and exploit the sensitivity of a methoxyacetophenone photosensitizer to increase the self-healing efficiency of a rigid membrane material from beyond repairing to 85% recovery under the same conditions. The tensile strength of the self-healing material is 33.88 MPa, and the elastic modulus reaches 3 GPa after 80 min of photo-irradiation at 308 nm. The maximum thermogravimetric decomposition rate temperature exceeds 400 °C, exhibiting their excellent thermal stability. This strategy provides a novel and effective approach to endow rigid materials with high self-healing efficiency at benign conditions, and opens a new avenue to functionalise a wide range of rigid engineering materials.

研究领域: 材料科学 · 化学工程
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2024 · IF 7.7

Self-assembling gelatin based delivery of multienzyme activity nanozyme and photosensitizer for ROS storm based cancer therapy

Donghui Zhao,Yunhao Deng,Junyi Shi,Xinye Ni,Chaoqing Li,Yang Bai,Yang Xuan,Jianhao Wang

Nanozymes with multienzyme activity for reactive oxygen species (ROS) generation and intracellular redox imbalance are attractive strategy for cancer therapy. However, it is severely limited by low biocompatibility and catalytic efficiency, hypoxic and high levels of GSH in the tumor microenvironment. To address these issues, a copper doping carbon nanozyme (CC) with multienzyme activity was designed and integrated with photosensitizer Ce6 and gelatin to fabricate ROS amplifier (CCC). Gelatin endowed CCC with good biocompatibility, low hemolysis, and enzyme responsive degradation. CCC with high CAT-like, POD-like, OXD-like, and GSHox-like activities can induce the intracellular ROS storm formation to eliminate the cancer cells. The OXD-like activity and PDT performance mediated 1 O 2 generation was markedly potentiated by the CAT-like activity of CCC via catalyzing high expression of H 2 O 2 to generate O 2 . At the same time, a large amount of ·OH were produced through POD-like activity of CCC and GSH was depleted by the GSHox-like activities of CCC, resulting in a destructive ROS storm formation and cellular redox homeostasis disruption. Both in vivo and in vitro experiments showed that CCC displayed satisfactory anti-tumor activity and biocompatibility. Our work provides a novel strategy for the development of nanozyne enhanced photodynamic therapy of cancer.

研究领域: 生物医学工程 · 肿瘤学 · 材料科学
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