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Chlorin e6
Advanced Healthcare Materials · 2023 ·Vol. 12 ·期 20 ·2300184 · IF 10

Disulfide-Bridged Dendritic Organosilicas-Based Biodegradable Molecularly Imprinted Polymers for Multiple Targeting and pH/Redox-Responsive Drug Release toward Chemical/Photodynamic Synergistic Tumor Therapy

Shiwei Liu,Shuang Han,Yuzhuo Song,Ruonan Sun,Le Zhao,Chen Yan

In this study, a sialic acid (SA) and transferrin (TF) imprinted biodegradable disulfide bridging organosilicas-based drug delivery system (SS-DMONS/DOX-Ce6@MIPs) for targeted cancer therapy is constructed, for the first time. Disulfide bridged dendritic mesoporous organosilicas nanoparticles (SS-DMONs) not only enhance drug loading as the drug repository, but also provide enough specific surface area for the molecular imprinting shell to expose more degradation and imprinted sites on the surface. In addition,  S  S  can be disturbed in a highly reducing tumor microenvironment to achieve degradation. The biodegradable imprinting film, prepared with customized 2-amino- N -(3,4-dihydroxyphenethyl)-3-mercaptopropanamide and 4-mercaptophenylboronic acid as functional monomers, endows SS-DMONs with active targeting capacity, and responsive drug release through degradation under acidic and highly reductive tumor microenvironment. SS-DMONS/DOX-Ce6@MIPs after binding of TF can target tumor cells actively through multiple interactions, including the affinity between antigen and antibody, and the specific recognition between molecularly imprinted polymers and template molecules. Under laser irradiation the loaded chlorin e6 (Ce6) that can produce toxic reactive oxygen, combined with the doxorubicin (DOX), achieves chemical/photodynamic synergistic anticancer effects. SS-DMONS/DOX-Ce6@MIPs present excellent tumor targeting and dual-responsive drug release, which provides an effective strategy for chemical/photodynamic antitumor therapy.

研究领域: 生物材料学 · 肿瘤学 · 药剂学
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Advanced Science · 2021 ·Vol. 8 ·期 16 ·2100228 · IF 16.806

Photoacoustic Force-Guided Precise and Fast Delivery of Nanomedicine with Boosted Therapeutic Efficacy

Jun Wang,Tingting Li,Jen-Shyang Ni,Heng Guo,Tianyi Kang,Zeshun Li,Menglei Zha,Songbo Lu,Chen Zhang,Weizhi Qi,Lei Xi,Kai Li

Precise and efficient delivery of nanomedicine to the target site has remained as a major roadblock in advanced cancer treatment. Here, a novel photoacoustic force (PAF)-guided nanotherapeutic system is reported based on a near-infrared (NIR)-absorbing semiconducting polymer (SP), showing significantly improved tumor accumulation and deep tissue penetration for enhanced phototherapeutic efficacy. The accumulation of nanoparticles in 4T1 tumor-bearing mice induced by the PAF strategy displays a fivefold enhancement in comparison with that of the traditional passive targeting pathway, in a significantly shortened time (45 min vs 24 h) with an enhanced penetration depth in tumors. Additionally, a tumor-bearing mouse model is rationally designed to unveil the mechanism, indicating that the nanoparticles enter solid tumors through enhanced transportation across blood vessel barriers via both inter-endothelial gaps and active trans-endothelial pathways. This process is specifically driven by PAF generated from the nanoparticles under NIR laser irradiation. The study thus demonstrates a new nanotherapeutic strategy with low dose, enhanced delivery efficiency in tumor, and boosted therapeutic efficacy, opening new doors for designing novel nanocarriers.

研究领域: 生物医学工程 · 癌症治疗 · 纳米医学
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NPG Asia Materials · 2017 ·Vol. 9 ·期 5 ·e383 · IF 9.157

In vivo high-efficiency targeted photodynamic therapy of ultra-small Fe3O4@polymer-NPO/PEG-Glc@Ce6 nanoprobes based on small size effect

Yin Ting,Zhang Qian,Wu Haigang,Gao Guo,Shapter Joseph G,Shen Yulan,He Qiaozhi,Huang Peng,Qi Wen,Cui Daxiang

Effectively prolonging the residence time of nanoprobes in the tumor region and reducing the accumulation of nanoprobes in the vital organs (for example, lung, liver and spleen) is crucial for high-efficiency photodynamic therapy (PDT) of cancer. Herein, we systematically report an ultra-small and highly stable nanoplatform with diameters of 4, 8 and 13 nm that exhibited excellent photodynamic therapeutic efficacy using Fe 3 O 4 @polymer-NPO/PEG-Glc@Ce6 nanoprobes. Based on the small size effect, the nanoprobes displayed lower cytotoxicity and excellent biocompatibility. Owing to the synergistic virtues of markedly active targeting and intrinsic small size effect, the Fe 3 O 4 @P-NPO/PEG-Glc@Ce6 nanoprobes can effectively prolong their residence time in the tumor region and reduce accumulation in the normal organs. Benefitting from the small size effect, the synthesized Fe 3 O 4 @P-NPO/PEG-Glc@Ce6 nanoprobes exhibited excellent tumor-targeting capability and photodynamic therapeutic efficacy by inhibiting the growth of tumors in mice under visible red light irradiation with a relatively lower power. The successful application of the small size effect in Fe 3 O 4 @P-NPO/PEG-Glc@Ce6 nanoprobes to significantly improve the PDT efficiency in our strategy suggests new building blocks for PDT of tumors and paves a new way for clinical therapies and translation in the near future.

研究领域: 纳米医学 · 癌症治疗 · 材料科学
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ACS Applied Materials & Interfaces · 2017 · IF 7.504

Multifunctional Nanoplatform Based on Black Phosphorus Quantum Dots for Bioimaging and Photodynamic/Photothermal Synergistic Cancer Therapy

Yi Li,Zhiming Liu,Yuqing Hou,Guangcun Yang,Xixi Fei,Henan Zhao,Yanxian Guo,Chengkang Su,Zhen Wang,Huiqing Zhong,Zhengfei Zhuang,Zhouyi Guo

A multifunctional nanoplatform based on black phosphorus quantum dots (BPQDs) was developed for cancer bioimaging and combined photothermal therapy (PTT) and photodynamic therapy (PDT). BPQDs were functionalized with PEG chains to achieve improved biocompatibility and physiological stability. The as-prepared nanoparticles exhibite prominent near-infrared (NIR) photothermal and red-light-triggered photodynamic properties. The combined therapeutic application of PEGylated BPQDs were then performed in vitro and in vivo. The results demonstrate that the combined phototherapy significantly promote the therapeutic efficacy of cancer treatment in comparison with PTT or PDT alone. BPQDs could also serve as the loading platform for fluorescent molecules, allowing reliable imaging of cancer cells. In addition, the low cytotoxicity and negligible side effects to main organs were observed in toxicity experiments. The theranostic characteristics of PEGylated BPQDs provide an uplifting potential for the future clinical applications.

研究领域: 纳米技术 · 生物医学工程 · 癌症研究 · 材料科学
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Scientific Reports · 2016 ·Vol. 6 ·期 1 ·1-12 · IF 5.228

Superparamagnetic Fe3O4-PEG2K-FA@Ce6 Nanoprobes for in Vivo Dual-mode Imaging and Targeted Photodynamic Therapy

Yin Ting,Huang Peng,Gao Guo,Shapter Joseph G.,Shen Yulan,Sun Rongjin,Yue Caixia,Zhang Chunlei,Liu Yanlei,Zhou Sui,Cui Daxiang

The development of targeted nanoprobes is a promising approach to cancer diagnostics and therapy. In the present work, a novel multifunctional photo/magnet-diagnostic nanoprobe (MNPs-PEG 2K -FA@Ce6) has been developed. This nanoprobe is built using folic acid (FA), bifunctional polyethylene glycol (PEG 2K ) and photosensitizer chlorin e6 (Ce6). The MNPs-PEG 2K -FA@Ce6 nanoprobes are superparamagnetic, can be synthesized on a large scale by a one-pot hydrothermal process without further surface modification and are stable in an aqueous environment for eight months. Compared with free Ce6 nanoprobes in vitro studies, the MNPs-PEG 2K -FA@Ce6 nanoprobes significantly enhance cellular uptake efficiency and promote the effectiveness of photodynamic therapy (PDT) with the assistance of 633 nm laser irradiation. The unique nanoprobes show superior penetration and a retention time of more than six days with less accumulation in the liver allowing highly effective tumor recognition and monitoring. Additionally, there was little damage to healthy organs or tissues. These exciting new nanoprobes could be potential building blocks to develop new clinical therapies and translational medicine.

研究领域: 生物医学工程 · 癌症研究 · 分子影像学
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Advanced Science · 2025 · IF 14.1

A Real-Time Cell Death Self-Reporting Theranostic Agent for Dynamic Optimization of Photodynamic Therapy

Wei Bian,Qiyue Wang,Cui He,Pan Tao,Juanjuan Zheng,Yulu Zhang,Jing Li,Fangyuan Li,Hongyan Jia,Daishun Ling

The therapeutic efficiency of photodynamic therapy (PDT) hinges on the drug-light interval (DLI), yet conventional approaches relying on photosensitizer accumulation often lead to suboptimal irradiation and adverse side effects. Here, a real-time cell death self-reporting photodynamic theranostic nanoagent (CDPN) is presented that dynamically monitors extracellular potassium ion ([K⁺] ex ) fluctuations as direct indicators of tumor cell death. By exploiting [K⁺] ex dyshomeostasis associated with apoptosis and necrosis, CDPN combines a photosensitizer and a potassium-sensitive fluorophore within mesoporous silica nanoparticles, encapsulated by a K⁺-selective membrane for enhanced specificity. In vitro and in vivo studies validate that [K⁺] ex dynamics closely correlate with cell death, enabling precise evaluation of PDT efficacy and data-driven optimization of the DLI. Using a breast cancer model, CDPN-guided adjustments identify optimized DLI conditions, achieving significantly improved therapeutic outcomes. This study introduces a new paradigm for PDT, establishing a real-time, adaptable strategy for guiding treatment parameters and advancing precision oncology.

研究领域: 肿瘤学 · 生物医学工程 · 药理学
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FOOD CHEMISTRY · 2024 · IF 8.5

A novel sustainable photo/chemical magnetic nanomaterial effectively mitigates the allergenicity of phospholipase A2

Fukai Li,Enning Zhou,Min Wang,Fei Pan,Jian Zhou,Mengrui Yang,Tongtong Wang,Liang Li,Liming Wu,Qiangqiang Li

Reducing the allergenicity of edible insects is crucial for the comprehensive utilization of insect resources. Phospholipase A2 (PLA2) exists in various edible insects and mammalian tissues, which can cause serious allergic reactions. Herein, we constructed a magnetic nanocomposite with photo/chemical synergistic capability to mitigate the allergenicity of PLA2. The formation of prepared nanocomposite was systematically confirmed using various techniques. The nanocomposite exhibited uniform diameters, abundant functional groups, excellent magnetic capabilities. An effective photo/chemical method was established to reduce the allergenicity of PLA2 in vitro. The feasibility of the method was demonstrated through circular dichroism, fluorescence spectrum and IgE-binding analysis. The allergenicity and IgE-binding effect of PLA2 were significantly reduced due to conformational changes after nanomaterial treatment. These results demonstrate the sensitivity and effectiveness a strategy for reducing PLA2 allergenicity, providing a basis for development of nanomaterials to reduce the risk of novel food allergies in response to edible insect products.

研究领域: 纳米技术 · 过敏学 · 食品科学 · 材料科学
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ACS Applied Materials & Interfaces · 2021 · IF 9.229

Quantitative Analysis of Protein Corona on Precoated Protein Nanoparticles and Determined Nanoparticles with Ultralow Protein Corona and Efficient Targeting in Vivo

Zicheng Zhong,Senbiao Fang,Yan Li,Yuan Huang,Yue Zhang,Hao Chen,Jinzhi Zhang,Hang-Xing Wang,Huayu Xiong,Qichao Zou,Suxiao Wang

The protein corona on nanoparticles (NPs) is a critical problem that often screens the targeting molecules and becomes one of the key reasons for the lack of practical application in nanotherapy. It is critical to fully understand the mechanism of the nanoparticle–biological interactions to design the nanoparticle-based therapeutic agents. Some types of proteins can be precoated on the nanoparticles to avoid unwanted protein attachment; however, the ultralow level of protein corona is hard to achieve, and the relationship of the antifouling property of the precoated protein nanoparticles with protein conformation and protein–nanoparticle interaction energy has never been investigated. In this work, we provided the quantitative protein corona composition analysis on different precoated protein nanoparticles, and on the basis of the molecular simulation process, we found their antifouling property strongly depended on the interaction energy of the precoated protein–serum protein pair and the number of hydrogen bonds formed between them. Furthermore, it also depended on the nanoparticle–serum protein pair interaction energy and the protein conformation on the nanoparticle. The casein coated nanoparticle with the antifouling property was determined, and after aptamer conjugation and drug loading, they exhibited superior targeting and internalization behavior for photodynamic and photothermal therapy in vitro and in vivo. Our work adds to the understanding of the protein corona behavior of precoated protein nanoparticles, and the determined antifouling NP can potentially be used as a highly efficient nanodrug carrier.

研究领域: 生物医学工程 · 纳米医学 · 药物递送系统
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Bioengineering & Translational Medicine · 2022 ·Vol. 8 ·期 1 ·e10352 · IF 10.684

Microneedles loaded with glutathione-scavenging composites for nitric oxide enhanced photodynamic therapy of melanoma

Fan Jia,Weijiang Yu,Xinfang Li,Yonghang Chen,Youxiang Wang,Jian Ji

Photodynamic therapy (PDT) represents an attractive promising route for melanoma treatment. However, its therapeutic efficacy is compromised by inefficient drug delivery and high glutathione (GSH) levels in cancer cells. To overcome these challenges, microneedles (MNs) system loaded with GSH-scavenging nanocomposites was presented for nitric oxide (NO) enhanced PDT. The nanocomposites consisted of S -nitroso- N -acrylate penicillamine (SNAP; a NO donor) grafted fourth-generation polyamide amine dendrimer (G 4 ) and chlorin e6 (Ce6). Upon local insertion of polyvinylpyrrolidone MNs, G 4 -SNAP/Ce6 composites were fast delivered and significantly amplified the therapeutic effects during PDT, via GSH depletion and reactive nitrogen species generation. Even with a single administration and low power light exposure, MNs with G 4 -SNAP/Ce6 effectively halt the tumor progression. The system demonstrated better cancer ablation efficacy than Ce6 alone toward melanoma. The strategy may inspire new ideas for future PDT-related therapy for skin tumors.

研究领域: 肿瘤学 · 药学 · 生物医学工程
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BIOMEDICINE & PHARMACOTHERAPY · 2022 · IF 7.419

Targeted chemo-photodynamic therapy toward esophageal cancer by GSH-sensitive theranostic nanoplatform

Guodong Ren,ZiCheng Wang,Yafei Tian,Jinyao Li,Yingyu Ma,Liang Zhou,Chengwu Zhang,Lixia Guo,Haipeng Diao,Lihong Li,Li Lu,Sufang Ma,Zhifang Wu,Lili Yan,Wen Liu

As the sixth leading cause of cancer death, esophageal cancer is threatening the life of people worldwide. Traditional treatments, such as surgery, chemotherapy, radiotherapy, are facing always augmented challenges including invasion, multidrug resistance (MDR), off-target toxicity. Chemo & Photodynamic synergistic therapy represents one promising strategy for improved treatment efficiency. But it is still hindered by the lack of tumor targeting, deleterious side effects, and unfavorable microenvironment for photodynamic therapy (PDT). To overcome those obstacles, one theranostic nano-assambly drug, GCDs-Ce6/Pt-EGF, was designed and fabricated. Green fluorescence carbon dots (GCDs) with the excellent optical properties, modifiability and low toxicity were prepared as drug carrier. Epidermal growth factor (EGF) was conjugated to the nano-assembly to realize tumor specific targeting. Chlorin e6 (Ce6) in the presence of laser irradiation achieved PDT by generating proapoptosis reactive oxygen species (ROS). Moreover, Ce6 incorporated into GCDs endowed the nano-assambly imaging ability and facilitate image-guided therapy. Pt(IV), cisplatin prodrug, in the nano-assambly depleted the glutathione (GSH) of tumor microenvironment when it was reduced to cytotoxicity Pt(II). Compared with single treatment, GCDs-Ce6/Pt-EGF exhibited enhanced tumor cell killing capacity and better biosafety in vitro and in vivo , especially for EGFR bearing tumor. It paved ways for developing novel theranostic agent to be potentially applied in clinic.

研究领域: 癌症治疗 · 纳米技术 · 药物科学 · 生物医学工程
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CARBOHYDRATE POLYMERS · 2023 · IF 11.2

Diselenide-triggered hydroxyethyl starch conjugate nanoparticles with cascade drug release properties for potentiating chemo-photodynamic therapy

Ronghua Tan,Jing Ge,Congcong Wang,Ying Wan,Xiangliang Yang

A novel type of diselenide bond-bridged hydroxyethyl starch-doxorubicin conjugate, HES-SeSe-DOX, was synthesized via a specially designed multistep synthetic route. The optimally achieved HES-SeSe-DOX was further combined with photosensitizer, chlorin E6 (Ce6), to self-assemble into HES-SeSe-DOX/Ce6 nanoparticles (NPs) for potentiating chemo-photodynamic anti-tumor therapy via diselenide-triggered cascade actions. HES-SeSe-DOX/Ce6 NPs were observed to disintegrate through the cleavage or oxidation of diselenide-bridged linkages in response to the stimuli arising from glutathione (GSH), hydrogen peroxide and Ce6-induced singlet oxygen, respectively, as evidenced by the enlarged size with irregular shapes and cascade drug release. In vitro cell studies exhibited that HES-SeSe-DOX/Ce6 NPs in combination with laser irradiation effectively consumed intracellular GSH and promoted a large rise in levels of reactive oxygen species in tumor cells, actuating the disruption of intracellular redox balance and the enhanced chemo-photodynamic cytotoxicity against tumor cells. The in vivo investigations revealed that HES-SeSe-DOX/Ce6 NPs were inclined to accumulate in tumors with persistent fluorescence emission, inhibited tumor growth with high efficacy and had good safety. These findings demonstrate the potential of HES-SeSe-DOX/Ce6 NPs for use in chemo-photodynamic tumor therapy and suggest their viability for clinical translation.

研究领域: 肿瘤学 · 药剂学 · 生物医学工程
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Theranostics · 2023 · IF 12.4

Light-triggered photosynthetic engineered bacteria for enhanced-photodynamic therapy by relieving tumor hypoxic microenvironment

Chenyang Yin,ZeKun Wang,Chunxue Dai,Bangjia Yang,Weiyun Wang,Endong Yang,Feng Guo,Cundong Fan,Pu Zhang,Jikui Sun,Dongdong Sun

Background: Singlet oxygen ( 1 O 2 ) has received considerable research attention in photodynamic therapy (PDT) due to its cytotoxic solid features. However, the inherent hypoxic state of the tumor microenvironment (TME) leads to the meager 1 O 2 quantum yield of inorganic PDT reagents, and their application in vivo remains elusive. Methods: We developed a novel strategy to fabricate active photosynthetic bacteria/photosensitizer/photothermal agent hybrids for photosynthetic tumor oxygenation and PDT and PTT tumor therapy under different laser irradiation sources. Photosynthetic bacteria combined with Ce6 photosensitizer and Au NPs photothermal agent, the obtained Bac@Au-Ce6 effectively targets tumor tissues and further enhances the tumor accumulation of Au-Ce6. Results: The results showed that the Au-Ce6-loaded engineered bacteria (Bac@Au-Ce6) maintained the photosynthetic properties of Syne . After i.v. injection, Bac@Au-Ce6 efficiently aggregates at tumor sites due to the tumor-targeting ability of active Syne . With 660 nm laser irradiation at the tumor site, the photoautotrophic Syne undergoes sustained photosynthetic O 2 release and immediately activates O 2 to 1 O 2 via a loaded photosensitizer. PTT was subsequently imparted by 808 laser irradiations to enhance tumor killing further. Conclusions: This work provides a new platform for engineering bacteria-mediated photosynthesis to promote PDT combined with PTT multi-faceted anti-tumor.

研究领域: 生物医学工程 · 肿瘤学 · 纳米医学
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