EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2023
·
IF 6.7
Xiaofan Liu,Minghui Ma,Shuo Tian,Weicai Wang,Xuemei Li
The action pathways of starvation therapy and photodynamic therapy (PDT) do not exist in isolation and are usually related to tumor cell metabolism and immune regulation, which are of great significance in the treatment of malignant tumors. Here, a cancer-targeted “domino” cascade reactor is constructed for synergistic starvation therapy and amplifies photodynamic therapy by assembling hemin and glucose oxidase (GOx) into DNA hydrogel load with hypoxia-inducible factor 1α (HIF-1α) and photosensitizer chlorin e6 (Ce6). The cascade reactor has excellent biocompatibility and tumor targeting, which promotes PDT by reducing HIF-1α. At the same time, the G-quadruplex of AS1411 combined with hemin (AH) catalyzes the generation of oxygen from hydrogen peroxide to further improve the efficiency of PDT. The synergistic therapeutic effect of the cascade reactor is evaluated through in vivo and in vitro experiments, indicating that this cascade reactor has great potential advantages in the synergistic treatment of cancer.
研究领域:
生物医学工程
·
癌症治疗
·
纳米技术
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2024
·
IF 9.4
Guanghao Li,Yujun Bao,Hui Zhang,Jingchun Wang,Xiaodan Wu,Rui Yan,Zhiqiang Wang,Yingxue Jin
Tumor metastasis and recurrence are closely related to immune escape and hypoxia. Chemodynamic therapy (CDT), photodynamic therapy (PDT), and photothermal therapy (PTT) can induce immunogenic cell death (ICD), and their combination with immune checkpoint agents is a promising therapeutic strategy. Iron based nanomaterials have received more and more attention, but their low Fenton reaction efficiency has hindered their clinical application. In this study, Fe 3 O 4 -carbon dots complex (Fe 3 O 4 -CDs) was synthesized, which was modified with ferrocenedicarboxylic acid by amide bond, and crosslinked into Fe 3 O 4 -CDs@Fc nano complex. The CDs catalyzed the Fenton reaction activity of Fe 3 O 4 by helping to improve the electron transfer efficiency, extended the reaction pH condition to 7.4. The Fe 3 O 4 -CDs@Fc exhibit exceptional optical activity, achieving a thermal conversion efficiency of 56.43 % under 808 nm light and a photosensitive single-line state oxygen quantum yield of 33 % under 660 nm light. Fe 3 O 4 -CDs@Fc improved intracellular oxygen level and inhibited hypoxia-inducing factor (HIF-1 α ) by in-situ oxygen production based on Fenton reaction. The multimodal combination of Fe 3 O 4 -CDs@Fc (CDT/PDT/PTT) strongly induced immune cell death (ICD). The expression of immune-related protein and HIF-1 α was investigated by immunofluorescence method. In vivo, Fe 3 O 4 -CDs@Fc combined with immune checkpoint blocker (antibody PD-L1, αPD-L1) effectively ablated primary tumors and inhibited distal tumor growth. Fe 3 O 4 -CDs@Fc is a promising immune-antitumor drug.
研究领域:
纳米技术
·
癌症治疗
·
生物医学工程
·
免疫疗法
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2024
·
IF 9.4
Jianan Qiao,Shuhui Liu,Yanfeng Huang,Xiang Zhu,Chenyang Xue,Yan Wang,Hui Xiong,Jing Yao
Clinical pancreatic ductal adenocarcinoma (PDAC) treatment is severely limited by lack of effective KRAS suppression strategies. To address this dilemma, a reactive oxygen species (ROS)-responsive and PDAC-targeted nanodrug named Z/B-PLS was constructed to confront KRAS through dual-blockade of its downstream PI3K/AKT/mTOR and RAF/MEK/ERK for enhanced PDAC treatment. Specifically, photosensitizer zinc phthalocyanine (ZnPc) and PI3K/mTOR inhibitor BEZ235 (BEZ) were co-loaded into PLS which was constructed by click chemistry conjugating MEK inhibitor selumetinib (SEL) to low molecular weight heparin with ROS-responsive oxalate bond. The BEZ and SEL blocked PI3K/AKT/mTOR and RAF/MEK/ERK respectively to remodel glycolysis and non-canonical glutamine metabolism. ZnPc mediated photodynamic therapy (PDT) could enhance drug release through ROS generation, further facilitating KRAS downstream dual-blockade to create treatment-promoting drug delivery-therapeutic positive feedback. Benefiting from this broad metabolic modulation cascade, the metabolic symbiosis between normoxic and hypoxic tumor cells was also cut off simultaneously and effective tumor vascular normalization effects could be achieved. As a result, PDT was dramatically promoted through glycolysis-non-canonical glutamine dual-metabolism regulation, achieving complete elimination of tumors in vivo . Above all, this study achieved effective multidimensional metabolic modulation based on integrated smart nanodrug delivery, helping overcome the therapeutic challenges posed by KRAS mutations of PDAC.
研究领域:
肿瘤学
·
药理学
·
纳米技术
·
代谢调控
·
光疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2018
·
IF 5.08
Meng Li,Ying Wang,Huiming Lin,Fengyu Qu
Here, hollow CuS nanocubes about 250–300 nm in size were synthesized based on the Kirkendall effect by using CuO nanocubeas precursor and template. The reactant concentration and reaction time could be adopted to adjust the final composition and hollow structure. The as-synthetic CuS nanocube was assembled by a great deal of nanoparticles (15–20 nm), making abundant porous structure in the shell layer. The localized surface plasmon resonance and the novel porous hollow structure (improve light reflex) further make sure the enhanced Near-infrared (NIR) light absorption as well as photothermal conversion efficiency (30.3%). Moreover, the mechanism of reactive oxygen species (ROS) generation was investigated in detail, revealing that the released Cu + ion and the oxygen are the determined factors. To further improve the monodispersity and biocompatibility, PEG-NH 2 modified nanostructure (CuS@PEG) was prepared and it possessed high loading efficiency to doxorubicin hydrochloride (DOX). Moreover, DOX-CuS@PEG reveals the acid and NIR sensitive-release performance. The synergistic effect of chemotherapy associated with photothermal therapy (PTT) and photodynamic therapy (PDT) display the enhanced specific cytotoxicity to cancer cells.
研究领域:
纳米技术
·
癌症治疗
·
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2016
·Vol. 26
·期 24
·4339-4350
·
IF 11.382
Guo-Feng Luo,Wei-Hai Chen,Qi Lei,Wen-Xiu Qiu,Yu-Xin Liu,Yin-Jia Cheng,Xian-Zheng Zhang
To integrate treatments of photothermal therapy, photodynamic therapy (PDT), and chemotherapy, this study reports on a multifunctional nanocomposite based on mesoporous silica-coated gold nanorod for high-performance oncotherapy. Gold nanorod core is used as the hyperthermal agent and mesoporous silica shell is used as the reservoir of photosensitizer (Al(III) phthalocyanine chloride tetrasulfonic acid, AlPcS 4 ). The mesoporous silica shell is modified with β-cyclodextrin (β-CD) gatekeeper via redox-cleavable Pt(IV) complex for controlled drug release. Furthermore, tumor targeting ligand (lactobionic acid, LA) and long-circulating poly(ethylene glycol) chain are introduced via host–guest interaction. It is found that the nanocomposite can specifically target to hepatoma cells by virtue of the LA targeting moiety. Due to the abundant existence of reducing agents within tumor cells, β-CD can be removed by reducing the Pt(IV) complex to active cisplatin drug for chemotherapy, along with the releasing of entrapped AlPcS 4 for effective PDT. As confirmed by in vitro and in vivo studies, the nanocomposite exhibits an obvious near-infrared induced thermal effect, which significantly improves the PDT and chemotherapy efficiency, resulting in a superadditive therapeutic effect. This collaborative strategy paves the way toward high-performance nanotherapeutics with a superior antitumor efficacy and much reduced side effects.
研究领域:
纳米技术
·
癌症治疗
·
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Nano Materials
·
2022
·
IF 6.14
Weicai Wang,Xiaozu Chen,Junwei Li,Qiu Jin,Hyung Jong Jin,Xuemei Li
Nanotechnology provides more developments and challenges for cancer immunotherapy. Nanomaterial-mediated synergistic therapy, immunosuppressive adjustment of the tumor microenvironment (TME), and nanovaccine construction can promote cancer immunotherapy. Here, based on the biodegradable hollow manganese dioxide (H-MnO2) tumor-targeted drug delivery platform, we have developed a TME-responsive nanovaccine for synergistic cancer therapy. The nanoplatform significantly enhanced photodynamic therapy (PDT)-mediated immune response by improving the hypoxic tumor microenvironment and on-demand drug release. At the same time, it was supplemented with gene therapy and chemotherapy to achieve significant in vivo combined therapy benefits. Taking full advantage of the high reactivity to the hydrogen peroxide and weak acidity of the TME, H-MnO2 loaded with chemotherapy drug doxorubicin (DOX) and photosensitizer chlorin e6 (Ce6) not only provided the required oxygen for photodynamic therapy but also reduced the side effects of chemotherapy drugs on normal tissues. Moreover, the coating of nucleic acid on H-MnO2 solved the problem of biocompatibility of nanoparticles and ensured that they could be swallowed by cancer cells. The results revealed that through the controlled release of targeted drugs and combined therapy, the synergistic nanovaccine significantly inhibited tumor growth in mice, which is expected to achieve the treatment of primary tumors.
研究领域:
纳米技术
·
癌症免疫治疗
·
药物递送系统
·
光动力疗法
·
基因治疗
·
化疗
·
生物相容性
✓ 已验证
DOI
高影响因子
Materials Today Bio
·
2022
·
IF 10.761
Yi Feng,Hanxi Zhang,Xiaoxue Xie,Yu Chen,Geng Yang,Xiaodan Wei,Ningxi Li,Mengyue Li,Tingting Li,Xiang Qin,Shun Li,Fengming You,Chunhui Wu,Hong Yang,Yiyao Liu
Therapeutic approaches of combining conventional photodynamic therapy (PDT) with other adjuvant treatments to sensitize PDT represent an appealing strategy. Herein, a novel synergetic “nanobomb” strategy based on glutathione (GSH)-responsive biodegradation was proposed to effectively destroy tumors expeditiously and accurately. This “nanobomb” was rationally constructed via the simultaneous encapsulation of methylene blue (MB) and l -arginine (L-Arg) into polyethylene glycol (PEG) modified mesoporous organosilicon nanoparticles (MON). The resulting L-Arg/ [email protected] initially exhibited prolonged blood circulation, improved bioavailability, and enhanced tumor accumulation in mice after tail vein injection according to the pharmacokinetic investigations, before the nanoparticles were entirely excreted. Under laser irradiation, L-Arg/ [email protected] produced remarkable reactive oxygen species (ROS) directly for PDT therapy, while a portion of ROS may oxidize L-Arg to generate nitric oxide (NO) not only for gas therapy (GT) but also serve as a biological messenger to regulate vasodilation to alleviate the tumor hypoxia. Subsequently, the rapidly released NO was further oxidized to reactive nitrogen species, which together with ROS promote immunogenic cell death by inducing G2/M cell-cycle arrest and apoptosis in cancer cells, and eventually resulting in enhanced anti-tumor immune responses. Moreover, the GSH depletion in tumor tissues induced by L-Arg/ [email protected] biodegradation can cooperate with GT to amplify the therapeutic effect of PDT. These results demonstrate that this “nanobomb” provides new ideas for clinical translation to treat tumor patients in terms of synergistic PDT-GT nanotherapy in hypoxic-solid tumors.
研究领域:
癌症治疗
·
纳米技术
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2022
·
IF 9.965
Ningyue Yu,Linzhou Zhao,Danling Cheng,Mengbin Ding,Yan Lyu,Jinhua Zhao,Jingchao Li
Theranostics with integrations of both imaging and therapeutic elements can enable early diagnosis and effective treatment of cancer. Herein, we report the development of radioactive semiconducting polymer nanoparticles (rSPNs) for multimodal cancer theranostics. Such rSPNs constructed through labeling poly(ethylene glycol) (PEG) grafted SPNs with iodine-131 ( 131 I) exhibit ideal photothermal property, excellent singlet oxygen ( 1 O 2 ) generating ability and good radiolabeling stability. Owing to their small particle dimension and PEG surface corona, rSPNs show an effective accumulation into subcutaneous tumors of living mice after systemic administration. The good fluorescence property and stable radiolabeling of rSPNs enable contrast signals for near-infrared (NIR) fluorescence and single photon emission computed tomography (SPECT) dual-model imaging of tumors. Moreover, rSPNs provide combinational action of photothermal therapy (PTT), photodynamic therapy (PDT) and radiotherapy under NIR laser irradiation, resulting in much higher therapeutic efficacy in inhibiting tumor growth and metastasis relative to SPNs-mediated treatment. This study thus offers a multifunctional organic nanosystem for multimodal cancer theranostics.
研究领域:
癌症诊疗学
·
放射学
·
纳米医学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2023
·
IF 10.2
Jie Lv,Xiaoyu Wang,Xue Zhang,Runpei Xu,Shuyang Hu,Shuangling Wang,Meng Li
Tumor microenvironment (TME) with the particular features of severe hypoxia, insufficient endogenous H 2 O 2 , and overexpression of glutathione (GSH) markedly reduced the antitumor efficacy of monotherapy. Herein, a TME-responsive multifunctional nanoplatform (Bi 2 S 3 @ [email protected] /Art NRs) was presented for synergistic photothermal therapy (PTT), chemodynamic therapy (CDT), and photodynamic therapy (PDT) to achieve better therapeutic outcomes. The Z-scheme heterostructured bismuth [email protected] nanorods (Bi 2 S 3 @Bi NRs) guaranteed excellent photothermal performance of the nanoplatform. Moreover, its ability to produce O 2 and reactive oxygen species (ROS) synchronously could relieve tumor hypoxia and improve PDT outcomes. The densely coated polydopamine/ammonium bicarbonate (PDA/ABC) and hyaluronic acid (HA) layers on the surface of the nanoplatform enhanced the cancer-targeting capacity and induced the acidic TME-triggered in situ “bomb-like” release of Art. The CDT treatment was achieved by activating the released Art through intracellular Fe 2+ ions in an H 2 O 2 -independent manner. Furthermore, decreasing the glutathione peroxidase 4 (GPX4) levels by Art could also increase the PDT efficiency of Bi 2 S 3 @Bi NRs. Owing to the synergistic effect, this nanoplatform displayed improved antitumor efficacy with minimal toxicity both in vitro and in vivo . Our design sheds light on the application of phototherapy combined with the traditional Chinese medicine monomer-artesunate in treating the hypoxic tumor.
研究领域:
纳米技术
·
癌症治疗
·
药学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2024
·
IF 5.3
Jie Li,Yufeng Gu,Wenwen Sun,Baoyu Wen,Bin Li,Jie Liu,Zhihong Sun,Qi Zhao,Chengming Sun
Triple-negative breast cancer (TNBC) poses a significant challenge owing to its complex pathological features and treatment resistance. In recent years, immune checkpoint blockade (ICB) therapy has shown satisfactory results in the treatment of TNBC. ICB therapy targeting T cells’ inhibitory receptors and innate immune checkpoints has gradually become a research hotspot. However, a study has found that compared with single immune checkpoint inhibition, dual ICB has a more significant therapeutic effect. This study aimed to develop an engineered nanocarrier, aLS@VpNPs, loaded with the photosensitizer verteporfin and coated with TNBC cell membranes loaded with antilymphocyte activation gene-3 (anti-LAG3) and sialic acid binding immunoglobulin-like lectin 10 (Siglec10) proteins for delivering combination therapies. The biomimetic vector can mimic the surface characteristics of tumor cells, showing better biocompatibility and efficient tumor-targeting ability. Under photodynamic therapy (PDT), reactive oxygen species (ROS) are generated at the tumor site to directly kill cancer cells and induce immunogenic cell death, transforming “cold tumors” into “hot tumors” and further enhancing the efficacy of dual ICB targeting T cells and macrophages. In summary, this approach improves drug delivery efficiency and therapeutic precision and activates the host immune system through the synergistic mechanisms of PDT and ICB. In addition, the study reveals potential mechanisms for the combined therapy in modulating the tumor microenvironment, offering effective strategies and directions for TNBC treatment.
研究领域:
肿瘤学
·
免疫治疗
·
纳米技术
·
癌症研究
·
治疗学
✓ 已验证
产品关联
DOI
高影响因子
Nanoscale
·
2024
·
IF 5.8
Xinru Kong,Yanxi Yang,Xueli Ren,Yandai Lin,Yu Shi,Zhe Liu
The concept of combining external medical stimuli with internal functional biomaterials to serve cancer-oriented treatments is emergingly developed. Optical and acoustical activations have shown special promises as non-invasive regulation modalities in cancer treatment and intervention. It is always challenging to leverage their contributions between optical and acoustical stimuli and find the appropriate biomaterials to optimally match them. Herein, a type of hybrid nanomicelles (ICG@PEP@HA) containing ICG as photo/sonosensitizers, an amphiphilic peptide for membrane penetration and hyaluronic acid for cluster determinant 44 (CD44) targeting were fabricated. Triggered by external stimuli of laser and US irradiations, their photo/sonothermal performances, in vitro reactive oxygen species (ROS) production capabilities and tumor-targeting efficiency have been systematically evaluated. It was interestingly found that the external stimulus of laser induced more quantity of ROS which resulted in a significant cell apoptosis and tumor growth inhibition in the presence of ICG@PEP@HA. The individual analysis and corresponding rationales have been investigated. In the meanwhile, these hybrid nanomicelles were administered into the MDA-MB-231 tumor-bearing nude mice for PDT and SDT therapies and their biocompatibility assessment, and a PDT prevailing efficacy and reliable bio-safety have been evidenced based on the hematological analysis and histochemical stainings. In summary, this study has validated a novel pathway to utilize these hybrid nanomicelles for laser/US-triggered localized tumor treatments, and the treatment efficiency may be leveraged by different external stimuli sources. It is also expected to give birth to full accessibility to clinical translations for human cancer treatments by means of as-reported laser/US-nanomicelles combination strategy.
研究领域:
纳米技术
·
癌症治疗
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Caiyun Xu,Junqin Li,Chunlei Ou,Jing Yang,Shuting Fu,Weiqing Hu,Li Wang,Zefeng Wang,Luo Hai,Le Deng,Dinggeng He
Chemodynamic therapy (CDT) involving highly toxic hydroxyl radical (•OH) with no drug resistance has gained widespread attention for antibacterial applications. However, the CDT effect is seriously confined by overexpressed glutathione (GSH) and limited hydrogen peroxide (H 2 O 2 ) in the infection sites. Here, we have constructed a cascade enzyme/nanozyme assembly (MCS/GOx) composing of a bimetallic sulfide MoCuS x (MCS) nanozyme loaded with natural glucose oxidase (GOx) for synergistic photothermal/photodynamic enhanced chemodynamic antimicrobial therapy with high performance. The loaded GOx can promote the peroxidase (POD)-like activity of MCS by providing an acidic microenvironment and self-supplying H 2 O 2 , achieving cascade generation of •OH for efficient CDT. The CDT effect can be further promoted by a co-catalysis mediated by the Mo 4+ /Mo 6+ redox couple. Upon exposure to an 808 nm near-infrared laser, MCS/GOx provides hyperpyrexia for photothermal antibacterial therapy (PTT), and produce singlet oxygen ( 1 O 2 ) for photodynamic therapy (PDT). Moreover, MCS/GOx can significantly consume antioxidant glutathione via the Cu + /Cu 2+ redox couple and PDT-mediated 1 O 2 production, thereby enhancing CDT antibacterial effect. In vitro experiments exhibit that MCS/GOx has combined antimicrobial effect against Staphylococcus aureus and Escherichia coli . Further in vivo studies demonstrate that MCS/GOx can efficiently eliminate bacterial cells in wound tissues and accelerate wound healing with low inflammatory response and good biosafety. Consequently, the proposed MCS/GOx with multiple bactericidal modalities shows a great potential in fighting wound infections.
研究领域:
纳米技术
·
生物医学工程
·
材料科学
·
药学
·
细菌学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）