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BIOCONJUGATE CHEMISTRY · 2021 · IF 4.774

MOFs-Derived Fe–N Codoped Carbon Nanoparticles as O2-Evolving Reactor and ROS Generator for CDT/PDT/PTT Synergistic Treatment of Tumors

Chunxiao Sui,Rui Tan,Yiwen Chen,Guotao Yin,Ziyang Wang,Wengui Xu,Xiaofeng Li

Metal–organic frameworks (MOFs) derivatives had been widely explored in electronic and environmental fields, but rarely evaluated in the biomedical applications. Herein, Fe–N codoped carbon (FeNC) nanoparticles were synthesized and characterized via facile pyrolysis of precursor ZIF-8 (Fe/Zn) nanoparticles, and their potential applications in tumor therapy were assessed in this investigation both in vitro and in vivo. After PAA (sodium polyacrylate) modification, the FeNC@PAA nanoparticles were able to initiate a Fe-based Fenton-like reaction to generate ·OH and O2 for chemodynamic therapy (CDT) and O2 evolution. Meanwhile, the porphyrin-like metal center in the FeNC@PAA nanoparticles could be used as a photosensitizer for photodynamic therapy (PDT) of tumors, which could be enhanced by O2 generated in CDT. Furthermore, the FeNC@PAA nanoparticles were also found to be effective in photothermal therapy (PTT) with a photothermal conversion efficiency of 29.15%, owing to a high absorbance in the near-infrared region (NIR). In conclusion, the synthesized FeNC@PAA nanoparticles exhibited promising applications in O2 evolution and CDT/PDT/PTT synergistic treatment of tumors.

研究领域: 生物医学工程 · 材料科学 · 肿瘤学
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Small · 2018 ·Vol. 14 ·期 52 ·1802994 · IF 9.598

Rational Design of IR820- and Ce6-Based Versatile Micelle for Single NIR Laser–Induced Imaging and Dual-Modal Phototherapy

Xu Hu,Hailong Tian,Wei Jiang,Aixin Song,Zhonghao Li,Yuxia Luan

Phototherapy as a promising cancer diagnostic and therapeutic strategy has aroused extensive attention. However, single-wavelength near-infrared (NIR) light–triggered combinational treatment of photothermal therapy (PTT) and photodynamic therapy (PDT) is still a great challenge. Herein, a multifunctional micelle activated by a single-wavelength laser for simultaneous PTT and PDT as well as fluorescence imaging is developed. Briefly, new indocyanine green (IR820) is conjugated to d -α-tocopheryl polyethylene glycol 1000 succinate (TPGS) via the linker 6-aminocaproic acid, and then, chlorin e6 (Ce6) is encapsulated into the micelles formed by TPGS–IR820 conjugates to fabricate TPGS–IR820/Ce6 micelles. As the well-designed TPGS–IR820 conjugate shares a similar peak absorption wavelength with Ce6, this micelle can be applied with a single NIR laser (660 nm). The stable micelles exhibit excellent photothermal conversion efficiency in vitro and in vivo as well as high singlet oxygen generation capacity in tumor cells. After efficient cellular internalization, the as-prepared micelles display outstanding anticancer activity upon single NIR laser irradiation in vitro and in vivo. Furthermore, TPGS–IR820/Ce6 micelles show negligible systemic toxicity. The highly safe and effective TPGS–IR820/Ce6 micelles can offer an innovative strategy to construct single NIR light–induced PTT and PDT combined phototherapy nanoplatforms via suitable modification of organic phototherapeutic agents.

研究领域: 癌症研究 · 诊疗学 · 材料科学 · 生物医学工程
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JOURNAL OF POLYMER RESEARCH · 2018 ·Vol. 25 ·期 12 ·1-12 · IF 1.434

Click synthesis of glycosylated porphyrin-cored PAMAM dendrimers with specific recognition and thermosensitivity

Chang Dan-Dan,Yang Wei-He,Dai Xiao-Hui,Wang Ji-Xiang,Chen Li,Pan Jian-Ming,Yan Yong-Sheng,Dai Yi-Rong

Glycoporphyrin dendrimers have received increasing attentions due to their distinct physical and chemistry properties, such as fluorescence and water solubility. They also acted as a promising photodynamic therapy (PDT) sensitizer and used in the study of carbohydrate-protein interaction. In this study, different generations of porphyrin-cored dendrimers consisting of glycosylated siloxane-poly (amido amine) typed dendron (PP-Si-PAMAM-D m -Lac, m = 1, 2, and 3), multifunctional specific-targeting sensitizers, had been synthesized via click reaction. The structure of PP-Si-PAMAM-D m -Lac was characterized by 1 H NMR, GPC, FT-IR, UV-vis and fluorescence analyses. This glycoporphyrin dendrimers, not only obtained high fluorescence quantum yield and singlet oxygen production efficiency, but also showed specific recognition of lectin and remarkable temperature-responsive property (20–80 °C). These properties proved a facile click synthetic strategy of glycosylated siloxane-poly (amido amine) typed dendrimers with multiple functions as a promising tumor-selective photsensitizer (PS) for PDT and also allow applications in highly sensitive fluorescent probes over a larger temperature window.

研究领域: 材料科学 · 化学 · 生物医学工程 · 纳米技术
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ACS Applied Materials & Interfaces · 2023 · IF 9.5

Platinum-Coordinated Engineered Nanoreactors with O2 Self-Amplificationand On-Demand Cascade Chemo-Drug Synthesis for Self-Reinforcing Hypoxic Oncotherapy

Qiuli Wang,Jiahao Meng,Lingling Huang,Feng Wu,Xue Yi,Guanghao Su,Ying Li,Zhenqing Hou,Zhongxiong Fan

How to efficiently synthesize toxic chemo-drugs in the hypoxia tumor microenvironment still faces a huge challenge. Herein, we have tailored engineered vehicle-free nanoreactors by coordination-driven co-assembly of photosensitizer indocyanine green (ICG), transition metal platinum (Pt), and nontoxic 1,5-dihydroxynaphthalene (DHN) to self-amplify O2 and cascade chemo-drug synthesis in tumor cells for self-reinforcing hypoxic oncotherapy. Once vehicle-free nanoreactors are internalized into tumor cells, they show a serious instability that results in rapid disassembly and on-demand drug release under the stimuli of acidic lysosome and laser radiation. Notably, the released Pt can efficiently decompose the endogenous hydrogen peroxide (H2O2) into O2 to alleviate tumor hypoxia, which is conducive to enhancing the photodynamic therapy (PDT) efficiency of the released ICG. Complementarily, a large amount of the 1O2 generated by PDT can efficiently oxidize the released nontoxic DHN into the highly toxic chemo-drug juglone. Therefore, such vehicle-free nanoreactors can achieve intracellular on-demand cascade chemo-drug synthesis and self-reinforce photo-chemotherapeutic efficacy on the hypoxic tumor. On the whole, such a simple, flexible, efficient, and nontoxic therapeutic strategy will broaden the study of on-demand chemo-drug synthesis and hypoxic oncotherapy.

研究领域: 癌症治疗 · 纳米医学 · 生物化学 · 材料科学
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JOURNAL OF NANOBIOTECHNOLOGY · 2024 ·Vol. 22 ·期 1 ·1-18 · IF 10.6

Iron-based MOF with Catalase-like activity improves the synergistic therapeutic effect of PDT/ferroptosis/starvation therapy by reversing the tumor hypoxic microenvironment

Chen Yukun,Chen Yuanyuan,Wang Zhenzhi,Yang Lian,Zhang Yu,Zhang Zhanxia,Jia Lijun

Reversing the hypoxic microenvironment of tumors is an important method to enhance the synergistic effect of tumor treatment. In this work, we developed the nanoparticles called Ce6@HGMOF, which consists of a photosensitizer (Ce6), glucose oxidase (GOX), chemotherapy drugs (HCPT) and an iron-based metal-organic framework (MOF). Ce6@HGMOF can consume glucose in tumor cells through “starvation therapy”, cut off their nutrition source, and produce gluconic acid and hydrogen peroxide (H 2 O 2 ). Utilizing this feature, Ce6@HGMOF can produce oxygen through catalase-like catalytic activity, thereby reversing the hypoxic microenvironment of tumors. This strategy of changing the hypoxic environment can help to slow down the growth of tumor blood vessels and improve the drug-resistant microenvironment to some extent. Meanwhile, increasing the supply of oxygen can enhance the effect of photodynamic therapy (PDT) and enhance the oxidative stress damage caused by reactive oxygen species (ROS) in tumor cells. On the other hand, cancer cells usually produce higher levels of glutathione (GSH) to adapt to high oxidative stress and protect themselves. The Ce6@HGMOF we designed can also consume GSH and induce ferroptosis of tumor cells through Fenton reaction with H 2 O 2 , while enhancing the effect of PDT. This innovative synergistic strategy, the combination of PDT/ferroptosis /starvation therapy, can complement each other and enhance each other. It has great potential as a powerful new anti-tumor paradigm in the future.

研究领域: 纳米技术 · 癌症治疗 · 生物医学工程 · 药学 · 材料科学
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Journal of Materials Chemistry B · 2020 ·Vol. 8 ·期 46 ·10650-10661 · IF 5.344

Black phosphorus quantum dots encapsulated in anionic waterborne polyurethane nanoparticles for enhancing stability and reactive oxygen species generation for cancer PDT/PTT therapy

Fengying Lu,Zhengjun Li,Yong Kang,Zhiguo Su,Rong Yu,Songping Zhang

Black phosphorus quantum dots (BPQDs) with excellent biocompatibility, outstanding photothermal and photodynamic efficacies have attracted significant attention in cancer therapy. However, the low environmental stability and poor dispersity of BPQDs limit their practical applications. In the present work, biocompatible anionic waterborne polyurethane (WPU) nanoparticles were synthesized from castor oil to encapsulate the BPQDs. The WPU–BPQDs with a BPQDs loading capacity of about 13.8% (w/w) exhibited significantly improved dispersion and environmental stability without affecting the photothermal efficiency of BPQDs. Intriguingly, it was found that WPU encapsulation led to significant enhancement in the reactive oxygen species (ROS) generation of BPQDs, which indicated the enhanced photodynamic efficacy of the encapsulated BPQDs as compared to the bare BPQDs. The effect of solution pH on the ROS generation efficiency of BPQDs and the pH variation caused by BPQDs degradation was then investigated to explore the possible mechanism. In acidic solution, ROS generation was suppressed, while BPQDs degradation led to the acidification of the solution. Fortunately, after being encapsulated inside the WPU nanoparticles, the degradation rate of BPQDs became slower, while the acidic environment around BPQDs was favorably regulated by WPU nanoparticles having a special electrochemical double layer consisting of interior COO− and exterior NH(Et3)+, thus endowing the WPU–BPQDs-boosted production of ROS as compared to the bare BPQDs. Considering the undesired acidic tumor environment, this unique pH regulation effect of WPU–BPQDs would be beneficial for in vivo photodynamic efficacy. Both in vitro and in vivo experiments showed that WPU–BPQDs could effectively improve photodynamic therapy (PDT) and maintain outstanding photothermal therapy (PTT) effects. Together with the excellent dispersity, biocompatibility, and easy biodegradability, WPU–BPQDs can be a promising agent for PDT/PTT cancer treatments.

研究领域: 纳米医学 · 癌症治疗 · 材料科学 · 生物医学工程
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Biomaterials Science · 2022 ·Vol. 10 ·期 11 ·2857-2864 · IF 7.59

Green synthesis of broccoli-derived carbon quantum dots as effective photosensitizers for the PDT effect testified in the model of mutant Caenorhabditis elegans

Shereen M. Elsherbiny,Changsheng Shao,Adolf Acheampong,Mahmoud A. Khalifa,Chao Liu,Qing Huang

The clinical application of photodynamic therapy (PDT) is still limited because of the drawbacks of the traditional photosensitizers, such as low singlet oxygen (1O2) quantum yield and the problem of photobleaching. Herein, carbon quantum dots (CQDs) derived from broccoli natural biomass as a carbon source were fabricated via a simple hydrothermal method and showed outstanding PDT ability as an effective photodynamic agent tested in Caenorhabditis elegans (C. elegans) models. The as-prepared broccoli-derived CQDs (BCQDs) showed excellent water solubility and optical properties and could generate singlet oxygen (1O2) effectively under irradiated light with a wavelength of 660 nm. The in vivo experiment revealed that the PDT efficiency of the BCQDs was dependent on the induction of germline apoptosis through the cep-1/p53 pathway. Further investigation confirmed the DNA damage of the worm by the BCQDs after sufficient light irradiation, which was tested by measuring the egl-1-fold induction in hus-1(op244), and cep-1(w40) mutants that have a loss of function in the genes involved in DNA damage response such as hus-1 (DNA checkpoint gene) and cep-1/p53 (tumor suppressor). The lack of germline apoptosis in the loss of function mutants egl-1(n487), hus-1(op244), and cep-1(w40) exposed to light irradiation compared with the control proved the necessity of these genes in DNA damage-induced germline apoptosis. Therefore, this work has not only provided a new photodynamic agent but also introduced C. elegans as an easy and high-throughput model for the rapid evaluation of the efficiency of PDT.

CAS / MDL: 57-88-5 7487-88-9
研究领域: 生物医学 · 分子生物学 · 纳米材料科学
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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Two birds with one stone: A multi-functional nanoplatform for sensitive detection and real-time inactivation of pathogenic bacteria with NIR-triggered PTT/PDT

Xianqing Huang,Yana Fu,Yicheng Guo,Yuzheng Cai,Tiange Li,Peijun Zhao,Yan Ma,Lianjun Song,Tianlin Wang

Given the increase in public safety incidents due to bacterial infections, sensitive detection and real-time inactivation of pathogenic bacteria have garnered increasing attention in the field of food safety, clinical diagnosis, and environmental monitoring. In this study, we constructed a “two-in-one” PB@DPA-Ce-GMP@Van (PCV) nanoplatform possessing enzyme-like properties and photothermal therapeutic (PTT) and photodynamic therapeutic (PDT) abilities for the detection and inactivation of pathogenic bacteria. PCV was captured on the surface of S. aureus to form a PCV/S. aureus complex. After centrifugation, PCV suspensions could catalyze non-fluorescent Amplex Red (AR) into fluorescent substrates and fluorescent scopolamine (SC) into non-fluorescent substrates. Hence, a ratiometric fluorescence probe with SC/AR reading was constructed for the sensitive detection of bacteria. The detection range reached 10 1 –10 7 colony-forming unit (CFU)/mL, and the detection limit was as low as 5.0 CFU/mL. Furthermore, approximately 99.7 % of free S. aureus can be inactivated by the PTT and PDT abilities of PCV. Thus, this nanoplatform exhibits a novel advantage in detecting and inactivating bacteria. Moreover, the bacterial infection wound model indicated that PVC exerts good disinfection ability. This study is of immense significance in the application of targeted sensing, eliminating bacterial infection, and even clinical therapy.

研究领域: 生物医学工程 · 食品安全 · 微生物学
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ADVANCED FUNCTIONAL MATERIALS · 2024 · IF 18.5

Bimetallic Nanozymes-Integrated Parachute-Like Au2Pt@PMO@ICG Janus Nanomotor with Dual Propulsion for Enhanced Tumor Penetration and Synergistic PTT/PDT/CDT Cancer Therapy

Xiaolei Zhang,Yangsai Lyu,Jia Li,Xiaohan Yang,Ziwei Lan,Zhixu Chen

Nanocatalytic therapeutic agents with triple synergistic treatment modes of chemodynamic therapy (CDT), photothermal therapy (PTT) and photodynamic therapy (PDT) are emerging nanomaterials in malignancy treatment. Nevertheless, the passive diffusion and transport of nanomaterials result in poor permeability in tumor lesions, severely affecting the effectiveness of synergistic therapy. Herein, a dual-source-driven parachute-like Au 2 Pt@PMO@ICG Janus nanomotor (APIJNS) is prepared by an interfacial energy-mediated anisotropic growth strategy for PTT-mediated CDT/PDT triple synergistic cancer therapy. Such nanomotor can realize self-thermophoresis drive under the trigger of near-infrared light, which can effectively enhance the active permeability and uptake of the APIJNS in the tumor tissue, thus achieving efficient PTT/PDT/CDT synergistic therapeutic effect. In addition, parachute-like APIJNS exhibits high-efficiency catalase (CAT)-like activity and can catalyze the overexpressed H 2 O 2 in the tumor microenvironment (TME) to generate oxygen (O 2 ), not only alleviating the hypoxia in the tumor lesion, but also converting it into singlet oxygen ( 1 O 2 ) to activate the photosensitizer ICG, achieving PDT. This work provides new ideas for enhancing triple synergistic cancer therapy by improving tumor permeability with dual-drive Janus nanomotors based on dual noble metal nanozymes.

研究领域: 纳米技术 · 生物医学工程 · 癌症治疗 · 材料科学 · 光热治疗 · 光动力治疗 · 化学动力治疗
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ACS Applied Materials & Interfaces · 2016 · IF 7.145

Tumor-Homing and Penetrating Peptide-Functionalized Photosensitizer-Conjugated PEG-PLA Nanoparticles for Chemo-Photodynamic Combination Therapy of Drug-Resistant Cancer

Xingye Feng,Di Jiang,Ting Kang,Jianhui Yao,Yixian Jing,Tianze Jiang,Jingxian Feng,Qianqian Zhu,Qingxiang Song,Nan Dong,Xiaoling Gao,Jun Chen

The combination of photodynamic therapy (PDT) and chemotherapy holds great potential in combating drug-resistant cancers. However, the major challenge that lies ahead is how to achieve high coloading capacity for both photosensitizer and chemo-drugs and how to gain efficient delivery of drugs to the drug-resistant tumors. In this study, we prepared a nanovehicle for codelivery of photosensitizer (pyropheophorbide-a, PPa) and chemo-drugs (paclitaxel, PTX) based on the synthesis of PPa-conjugated amphiphilic copolymer PPa-PLA-PEG-PLA-PPa. The obtained nanoparticles (PP NP) exhibited a satisfactory high drug-loading capacity for both drugs. To achieve effective tumor-targeting therapy, the surface of PP NP was decorated with a tumor-homing and penetrating peptide F3. In vitro cellular experiments showed that F3-functionalized PP NP (F3-PP NP) exhibited higher cellular association than PP NP and resulted in the strongest antiproliferation effect. In addition, compared with the unmodified nanoparticles, F3-PP NP exhibited a more preferential enrichment at the tumor site. Pharmacodynamics evaluation in vivo demonstrated that a longer survival time was achieved by the tumor-bearing mice treated with PP NP (+laser) than those treated with chemotherapy only or PDT only. Such antitumor efficacy of combination therapy was further improved following the F3 peptide functionalization. Collectively, these results suggested that targeted combination therapy may pave a promising way for the therapy of drug-resistant tumor.

CAS / MDL: 538-75-0 1122-58-3
研究领域: 肿瘤学 · 药学 · 纳米技术 · 癌症治疗
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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
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CHEMISTRY OF MATERIALS · 2019 · IF 10.159

Covalent Organic Nanosheets Integrated Heterojunction with Two Strategies To Overcome Hypoxic-Tumor Photodynamic Therapy

Kui Wang,Zhe Zhang,Lin Lin,Jie Chen,Kai Hao,Huayu Tian,Xuesi Chen

Photodynamic therapy (PDT) still faces a key challenge associated with its oxygen-dependent property, which limits its therapeutic efficiency against hypoxic tumor. To address the problem, covalent organic nanosheets (CONs) are prepared with a donor–acceptor molecular heterostructure. CONs can address the hypoxic-tumor PDT by two strategies, that is, type I PDT and type I PDT combined with photothermal therapy (PTT). On the one hand, the molecular heterostructure of CONs can afford highly efficient charge carrier separation, a long lifetime of electrons and holes can be obtained, the electrons can reduce O2 to form O2·–, and at the same time, the holes can oxidize water to produce ·OH. Therefore, type I PDT is obtained, which can be used to diminish the limits of hypoxia in type II PDT. On the other hand, the recombination of photoexcited species results in an important nonradiative attenuation, and thus the energy is emitted as heat. A combination of type I PDT and PTT serves as an effective way to get around the difficulties of hypoxia in PDT. Intravenous injection of CONs in nude mice followed by the combination of type I PDT and PTT under single-wavelength irradiation achieves significant tumor ablation.

CAS / MDL: 30525-89-4 109-97-7
研究领域: 纳米技术 · 癌症治疗 · 材料科学 · 生物医学工程
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