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原卟啉IX (PpIX)
Frontiers in Chemistry · 2019 · IF 3.782

A Theranostic Nanoprobe for Hypoxia Imaging and Photodynamic Tumor Therapy

Fan Jing Hao,Fan Gui Ling,Yuan Ping,Deng Fu An,Liu Ling Shan,Zhou Xiang,Yu Xi Yong,Cheng Hong,Li Shi Ying

Hypoxia is a common feature for most malignant tumors, which was also closely related to the oxygen-dependent photodynamic therapy. Based on Förster resonance energy transfer (FRET), a smart nanoprobe (designated as H-Probe) was designed in this paper for hypoxia imaging and photodynamic tumor therapy. Due to the FRET process, H-Probe could respond to hypoxia with a significant fluorescence recovery. Moreover, abundant in vitro investigations demonstrated that the photosensitizer of PpIX in H-Probe could generate large amounts of singlet oxygen to kill cancer cells in the presence of oxygen and light with appropriate wavelength. Also, intravenously injected H-Probe with light irradiation achieved an effective tumor inhibition in vivo with a reduced side effect. This original strategy of integrating hypoxia imaging and tumor therapy in one nanoplatform would promote the development of theranostic nanoplatform for tumor precision therapy.

研究领域: 癌症研究 · 诊疗学 · 分子影像 · 纳米医学
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ACS Nano · 2015 · IF 12.881

Ratiometric Biosensor for Aggregation-Induced Emission-Guided Precise Photodynamic Therapy

Kai Han,Shi-Bo Wang,Qi Lei,Jing-Yi Zhu,Xian-Zheng Zhang

Photodynamic therapy faces the barrier of choosing the appropriate irradiation region and time. In this paper, a matrix metalloproteinase-2 (MMP-2) responsive ratiometric biosensor was designed and synthesized for aggregation-induced emission (AIE)-guided precise photodynamic therapy. It was found that the biosensor presented the MMP-2 responsive AIE behavior. Most importantly, it could accurately differentiate the tumor cells from the healthy cells by the fluorescence ratio between freed tetraphenylethylene and protoporphyrin IX (PpIX, internal reference). In vivo study demonstrated that the biosensor could preferentially accumulate in the tumor tissue with a relative long blood retention time. Note that the intrinsic fluorescence of PpIX and MMP-2-triggered AIE fluorescence provided a real-time feedback which guided precise photodynamic therapy in vivo efficiently. This strategy demonstrated here opens a window in the precise medicine, especially for phototherapy.

研究领域: 癌症研究 · 治疗诊断学 · 生物医学工程 · 分子影像
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Journal of Materials Chemistry B · 2021 ·Vol. 9 ·期 26 ·5255-5263 · IF 6.331

Oxygen-producing proenzyme hydrogels for photodynamic-mediated metastasis-inhibiting combinational therapy

Jiansheng Liu,Xueqin Qing,Qin Zhang,Ningyue Yu,Mengbin Ding,Zhaohui Li,Zhen Zhao,Zhiling Zhou,Jingchao Li

Photodynamic therapy (PDT) has provided a promising approach for the treatment of solid tumors, while the therapeutic efficacy is often limited due to the hypoxic tumor microenvironment, resulting in tumor metastasis. Herein, we report an oxygen-producing proenzyme hydrogel (OPeH) with photoactivatable enzymatic activity for PDT enabled metastasis-inhibiting combinational therapy of breast cancer. This OPeH based on alginate is composed of protoporphyrin IX (PpIX) conjugated manganese oxide (MnO2) nanoparticles, which act as both the photosensitizer and oxygen-producing agent, and singlet oxygen (1O2)-responsive proenzyme nanoparticles. In the hypoxic and acidic tumor microenvironment, MnO2 can generate 1O2 to promote PpIX-mediated PDT with an amplified 1O2 generation efficiency, which also triggers the cleavage of 1O2-responsive linkers and cascade activation of proenzymes for cancer cell death. This combinational therapy upon photoactivation not only greatly inhibited the tumor growth, but also suppressed lung metastasis in a mouse xenograft breast tumor model, which is impossible in the case of PDT alone. This study thus provides a proenzyme hydrogel platform with photoactivatable activity for metastasis-inhibiting cancer therapy with high efficacy and safety.

研究领域: 癌症治疗 · 纳米医学 · 生物医学工程 · 肿瘤微环境研究
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2020 · IF 4.389

Receptor-mediated photothermal/photodynamic synergistic anticancer nanodrugs with SERS tracing function

Ping Tang,Meishuang Xing,Xinyue Xing,Qiao Tao,Wendai Cheng,Shengde Liu,Xiaoxu Lu,Liyun Zhong

Phototherapy, especially the photothermal therapy (PTT) and the photodynamic therapy (PDT), have become very promising in cancer treatment due to its low invasiveness and high efficacy. Both PTT and PDT involve the utilization of light energy, and their synergistic treatment should be a good solution for cancer treatment by ingenious design. The therapeutic effect of phototherapy is closely associated with the amount and location of anticancer-nanodrugs accumulated in tumor cells, and the receptor-mediated endocytosis should be an excellent candidate for enhancing anticancer-nanodrugs internalization. Surface enhanced Raman spectroscopy (SERS) imaging is suitable for tracing nanodrugs due to its high selectivity, sensitivity and reliability. In this paper, we hope to construct a receptor-mediated PTT/PDT synergistic anticancer nanodrugs and evaluate the corresponding efficacy through SERS tracing function. Here, the receptor-mediated PTT/PDT synergistic anticancer nanodrugs are prepared by the chemical modification of gold nanorods (GNRs), involving protoporphyrin IX (PpIX), 4-mecaptobenzoic acid (MBA), and folic acid (FA). The achieved results show that the receptor-mediated endocytosis can greatly facilitate the internalized amount and intracellular distribution of the nanodrugs, thus lead to the anti-cancer efficacy improvement. Importantly, this receptor-mediated PTT/PDT synergistic treatment with SERS tracing function will provide a simple and effective strategy for the design and application of anticancer phototherapy nanodrugs.

CAS / MDL: 59-30-3
研究领域: 癌症治疗 · 纳米技术 · 生物医学工程 · 光学成像
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MATERIALS & DESIGN · 2024 · IF 7.6

Homologous tumor cell membrane-encapsulated methyl 5-aminolevulinate solid lipid nanoparticles for the precise localization of melanoma and sensitization by radiotherapy

Yanyan Meng,Shaoqing Chen,Pengyin Li,Cheli Wang,Xinye Ni

Melanoma is a highly invasive and lethal skin cancer with a strong tendency to metastasize and has a poor prognosis. Radiotherapy is one of the important treatments for melanoma. In this study, monoglyceride solid lipid nanoparticles (MG SLNs) were wrapped with the B16-F10 cell membrane (B16 CM) for the fabrication of B16@MG. B16@MG had low toxicity and specifically targeted B16-F10 cells. B16-F10 tumor–bearing mouse model showed that indocyanine green (ICG) -loaded B16@MG achieved long-term accumulation in the tumor and facilitated the localization of the tumor boundary. MG SLNs were encapsulated with methyl 5-aminolevulinate (MLA) and desferrioxamine (DFO), and B16 CM was wrapped around their surfaces to obtain B16@MG–MLA–DFO.MLA was metabolized to protoporphyrin IX (PpIX) in the cells and DFO reduced the content of iron ion in the cells, blocked the biotransformation of PpIX, and promoted the accumulation of PpIX in the cells. The results of mitochondrial reactive oxygen species (ROS) and membrane potential detection showed that PpIX enhanced the generation of ROS, caused DNA and mitochondrial damage, and led to the apoptosis of tumor cells under radiotherapy. In B16-F10 tumor–bearing mice, B16@MG–MLA–DFO can improve the efficacy of radiotherapy and allow the integration of diagnosis and treatment.

CAS / MDL: 79416-27-6 70-51-9
研究领域: 肿瘤学 · 纳米技术 · 药理学 · 放射生物学
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Nature Communications · 2023 ·Vol. 14 ·期 1 ·1-14 · IF 16.6

Continuous Spatiotemporal Therapy of A Full-API Nanodrug via Multi-Step Tandem Endogenous Biosynthesis

Fang Fang,Wang Sa,Song Yueyue,Sun Meng,Chen Wen-Cheng,Zhao Dongxu,Zhang Jinfeng

Nanomedicine holds great promise to enhance cancer therapy. However, low active pharmaceutical ingredient (API) loading content, unpredictable drug release, and potential toxicity from excipients limit their translational capability. We herein report a full-API nanodrug composed of FDA-approved 5-aminolevulinic acid (ALA), human essential element Fe 3+ , and natural bioactive compound curcumin with an ideal API content and pH-responsive release profile for continuous spatiotemporal cancer therapy achieved by multi-step tandem endogenous biosynthesis. First, ALA enzymatically converts into photosensitizer protoporphyrin IX (PpIX). Afterward, multiple downstream products including carbon monoxide (CO), Fe 2+ , biliverdin (BV), and bilirubin (BR) are individually biosynthesized through the PpIX-heme-CO/Fe 2+ /BV-BR metabolic pathway, further cooperating with released Fe 3+ and curcumin, ultimately eliciting mitochondria damage, membrane disruption, and intracytoplasmic injury. This work not only provides a paradigm for exploiting diversified metabolites for tumor suppression, but also presents a safe and efficient full-API nanodrug, facilitating the practical translation of nanodrugs.

研究领域: 纳米医学 · 癌症研究 · 药学 · 生物医学工程
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JOURNAL OF CONTROLLED RELEASE · 2023 · IF 10.8

Prodrug-based strategy with a two-in-one liposome for Cerenkov-induced photodynamic therapy and chemotherapy

Huihui Liu,Qing Wang,Jingru Guo,Kai Feng,Yiling Ruan,Zhihao Zhang,Xin Ji,Jigang Wang,Tao Zhang,Xiaolian Sun

Cerenkov radiation induced photodynamic therapy (CR-PDT) can tackle the tissue penetration limitation of traditional PDT. However, co-delivery of radionuclides and photosensitizer may cause continuous phototoxicity in normal tissues during the circulation. 5-aminolevulinic acid (ALA) which can intracellularly transform into photosensitive protoporphyrin IX (PpIX) is a cancer-selective photosensitizer with negligible side effect. However, the hydrophilic nature of ALA and the further conversion of PpIX to photoinactive Heme severely hinder the therapeutic benefits of ALA-based PDT. Herein, we developed an 89 Zr-labeled, pH responsive ALA and artemisinin (ART) co-loaded liposome ( 89 Zr-ALA-Liposome-ART) for highly selective cancer therapy. 89 Zr can serve as the internal excitation source to self-activate PpIX for CR-PDT, and the photoinactive Heme can activate the chemotherapeutic effect of ART. The 89 Zr-ALA-Liposome-ART exhibited excellent tumor inhibition capability in subcutaneous 4T1-tumor-bearing Balb/c mice via CR-PDT and chemotherapy. Combined with anti-PD-L1, the 89 Zr-ALA-Liposome-ART elicited strong antitumor immunity to against tumor recurrence.

CAS / MDL: 63968-64-9 7803-57-8
研究领域: 药学 · 放射肿瘤学 · 纳米技术 · 免疫疗法
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