ACS Applied Materials & Interfaces
·
2018
·
IF 8.097
Xiang-long Tang,Feng Jing,Ben-lan Lin,Sheng Cui,Ru-tong Yu,Xiao-dong Shen,Ting-wei Wang
By overcoming drug resistance and subsequently enhancing the treatment, the combination therapy of photodynamic therapy (PDT) and chemotherapy has promising potential for cancer treatment. However, the major challenge is how to establish an advanced nanoplatform that can be efficiently guided to tumor sites and can then stably release both chemotherapy drugs and a photosensitizer simultaneously and precisely. In this study, which considered the possibility and targeting efficiency of a magnetic targeting strategy, a novel Fe3O4@mSiO2(DOX)@HSA(Ce6) nanoplatform was successfully built; this platform could be employed as an efficient synergistic antitumor nanoplatform with magnetic guidance for highly specific targeting and retention. Doxorubicin (DOX) molecules were loaded into mesoporous silica with high loading capability, and the mesoporous channels were blocked by a polydopamine coating. Human serum albumin (HSA) was conjugated to the outer surface to increase the biocompatibility and blood circulation time, as well as to provide a vehicle for loading photosensitizer chlorin e6 (Ce6). The sustained release of DOX under acidic conditions and the PDT induced by red light exerted a synergistic inhibitory effect on glioma cells. Our experiments demonstrated that the pH-responsive Fe3O4@mSiO2(DOX)@HSA(Ce6) nanoplatform was guided to the tumor region by magnetic targeting and that the nanoplatform suppressed glioma tumor growth efficiently, implying that the system is a highly promising photodynamic therapy/chemotherapy combination nanoplatform with synergistic effects for cancer treatment.
研究领域:
纳米技术
·
癌症研究
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生物医学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2023
·
IF 9.7
Shao-Yi Chen,Lin-Ping Zhao,Zu-Xiao Chen,Chu-Yu Huang,Ren-Jiang Kong,Yu-Qing Wang,Da-Wei Zhang,Shi-Ying Li,Hui-Hui Ti,Hong Cheng
ABSTRACT Reactive oxygen species (ROS) generated during photodynamic therapy (PDT) can induce autophagy to protect tumor cell from PDT-induced apoptosis. In this work, a self-delivery autophagy regulator (designated as CeCe) is developed for autophagy promotion sensitized PDT against tumor. Briefly, CeCe is prepared by the assembly of a photosensitizer of chlorin e6 (Ce6) and autophagy promoter of celastrol. By virtue of intermolecular interactions, Ce6 and celastrol are able to self-assemble into nanomedicine with great photodynamic performance and autophagy regulation capacity. Under light irradiation, CeCe would produce ROS in tumor cells to amplify the oxidative stress and promote cell autophagy. As a result, CeCe exhibits an enhanced photo toxicity by inducing autophagic cell death. In vivo experiments indicate that CeCe can predominantly accumulate in tumor tissue for a robust PDT. Moreover, CeCe has a superior therapeutic efficiency compared to monotherapy and combined treatment of Ce6 and celastrol, suggesting a synergistic antitumor effect of PDT and autophagy promotion. This self-delivery nanomedicine may advance the development of the co-delivery nanoplatform to improve the antitumor efficacy of PDT by promoting autophagy. Statement of Significance Autophagy is a “double-edged sword” in cellular homeostasis and metabolism, which can promote tumor progression but also induce an unknown impact on tumor inhibition. In this work, a self-delivery autophagy regulator (designated as CeCe) was developed for autophagy promotion sensitized photodynamic therapy (PDT). By virtue of intermolecular interactions, Ce6 and celastrol were found to self-assemble into stable CeCe without drug excipients, which exhibited great photodynamic performance and autophagy regulation capacity. In vitro and in vivo findings demonstrated a superior tumor suppression ability of CeCe over the monotherapy as well as the combined treatment of Ce6 and celastrol, suggesting a synergistic antitumor efficacy by PDT and autophagy promotion.
研究领域:
生物医学工程
·
癌症研究
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纳米技术
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Autophagy
·
2019
·
IF 11.059
Fei Qu,Pan Wang,Kun Zhang,Yin Shi,Yixiang Li,Chengren Li,Junhan Lu,Quanhong Liu,Xiaobing Wang
Limited penetration of chemotherapeutic drugs through the blood brain barrier (BBB), and the increased chemo-resistance of glioma cells due to macroautophagy/autophagy, result in high tumor recurrence and extremely limited survival of glioma patients. Ultrasound-targeted microbubble destruction (UTMD) is a technique of transient and reversible BBB disruption, which greatly facilitates intracerebral drug delivery. In addition, sonodynamic therapy (SDT) based on ultrasound stimulation and a sonosensitizer, can be a safe and noninvasive strategy for treating glioma. We innovatively designed a smart “all-in-one” nanosensitizer platform by incorporating the sonoactive chlorin e6 (Ce6) and an autophagy inhibitor-hydroxychloroquine (HCQ) into angiopep-2 peptide-modified liposomes (designated as ACHL), which integrates multiple diagnostic and therapeutic functions. ACHL selectively accumulated in the brain tumors during the optimal time-window of transient UTMD-mediated BBB opening. The nanosensitizer then responded to a second ultrasonic stimulation, and simultaneously unloaded HCQ and generated ROS in the glioma cells. The sonotherapy triggered apoptosis as well as MAPK/p38-PINK1-PRKN-dependent mitophagy, in which the antioxidant relieved the sonotoxicity and MAPK/p38 activation, while the inhibition of MAPK/p38 attenuated the progression toward mitophagy by compromising redistribution of PRKN. Moreover, HCQ blocking autophagosome degradation, augmented intracellular ROS production and resulted in an oxidative-damage regenerative loop. ACHL-SDT treatment using this construct significantly inhibited the xenograft-tumor growth and prolonged the survival time of tumor-bearing mice, exhibiting an improved therapeutic efficiency. All together, we demonstrated a precision sonotherapy with simultaneous apoptosis induction and mitophagy inhibition, which served as an intelligently strategic sense of working alongside, providing new insights into the theranostics of brain tumors.Abbreviations ACHL: Angiopep-2-modified liposomes loaded with Ce6 and hydroxychloroquine; ACL: Angiopep-2-modified liposomes loaded with Ce6; BBB: blood brain barrier; Ce6: chlorin e6; CHL: liposomes loaded with Ce6 and hydroxychloroquine; CL: liposomes loaded with Ce6; CNS: central nervous system; DDS: drug delivery system; EB: Evans blue; FUS: focused ultrasound; HCQ: hydroxychloroquine; LRP1: low density lipoprotein receptor-related protein 1; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MAPK: mitogen-activated protein kinase; MBs: microbubbles; MTG: MitoTracker Green; MTR: MitoTracker Red; MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; PBS: phosphate-buffered saline; PDI: polydispersity index; PINK1: PTEN induced kinase 1; PRKN/parkin: parkin RBR E3 ubiquitin protein ligase; ROS: reactive oxygen species; SDT: sonodynamic therapy; SQSTM1: sequestome 1; TA: terephthalic acid; TEM: transmission electron microscopy; TUNEL: terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling; US: ultrasound; UTMD: ultrasound-targeted microbubble destruction.
研究领域:
神经科学
·
肿瘤学
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纳米技术
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治疗诊断学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2024
·
IF 4.5
Fang Ning,Dengshuai Wei,Hongli Yu,Tingting Song,Zhipeng Li,Hongmei Ma,Yong Sun
Inhibition of autophagy increases the sensitivity of tumor cells to radiotherapy and chemotherapy and improves the therapeutic effect on tumors. Recently, photodynamic therapy (PDT) combined with chemotherapy has been proven to further improve the efficiency of cancer treatment. As such, combining autophagy inhibition with PDT and chemotherapy may represent a potentially effective new strategy for cancer treatment. However, currently widely studied autophagy inhibitors inevitably produce various toxic side effects due to their inherent pharmacological activity. To overcome this constraint, in this study, we designed an ideal multifunctional upconversion nanoplatform, UCNP-Ce6-EPI@mPPA + NIR (MUCEN). Control, UCNP-EPI@mPPA (MUE), UCNP-EPI@mPPA + NIR (MUEN), Ce6-EPI@mPPA (MCE), Ce6-EPI@mPPA + NIR (MCEN), and UCNP-Ce6-EPI@mPPA (MUCE) groups were set up separately as controls. Based on a combination of autophagy inhibition and PDT, the average particle size of MUCEN was 197 nm, which can simultaneously achieve the double encapsulation of chlorine e6 (Ce6) and epirubicin (EPI). In vitro tests revealed that MUCE was efficiently endocytosed by 4T1 cells under near-infrared light irradiation. Further, in vivo tests revealed that MUCE dramatically inhibited tumor growth. Immunohistochemistry results indicated that MUCE efficiently increased the expression of autophagy inhibitors p62 and LC3 in tumor tissues. The synergistic effect of autophagy inhibition and PDT with MUCE exhibited superior tumor suppression, providing an innovative approach to cancer treatment.
研究领域:
纳米技术
·
癌症研究
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生物医学工程
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Huilan Zhuang,Panpan Xue,Sijie Shao,Xuemei Zeng,Shuangqian Yan
Ferroptosis has drawn great attention to tumor treatments over the past decade. However, how to specifically boost tumoral redox imbalance by simultaneously superimposing iron-mediated reactive oxygen species and undermining antioxidative pathways at the tumor site is still a significant challenge in ferroptosis-based tumor ferrotherapy. In this study, we designed an in situ generable hydrogel that contains paclitaxel/chlorin e6-loaded iron-based metal-organic framework (Fe-MOF) nanoparticles for enhanced breast tumor ferrotherapy by multiplex magnifying redox imbalance. The polysaccharide sodium alginate can crosslink with tumoral calcium ions to generate a hydrogel patch, which promotes the retention of Fe-MOF and therapeutic molecules. The Fe-MOF holds peroxidase/glutathione oxidase mimicking properties, resulting in OH generation via the Fenton reaction and glutathione consumption. Local ultrasound treatment facilitates the release of therapeutics and stimulates the generation of signet oxygen by activating the sonosensitizer chlorin e6. In the meanwhile, the low-dose paclitaxel reduces tumoral pH value by downregulating the glutaminolysis-related gene (SLC7A11) which in turn enhances the catalytic activity of Fe-MOF and inhibits antioxidative pathways, respectively. Both in vivo and in vitro experiments show that our designed hybrid hydrogels can induce significant ferrotherapeutic effects by augmenting the tumoral oxidative stresses .
研究领域:
肿瘤学
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材料科学
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生物医学工程
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治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
APPLIED CATALYSIS B-ENVIRONMENTAL
·
2021
·
IF 19.503
Xinyu Bai,Qidong Hou,Hengli Qian,Yifan Nie,Tianliang Xia,Ruite Lai,Guanjie Yu,Mian Laiq Ur Rehman,Haijiao Xie,Meiting Ju
Photocatalysis has exhibited huge potential in many reactions, but the design of metal-free photocatalytic material for selective upgrading of biomass is rarely achieved. Here, we report that the metal-free photocatalyst consisted of nitrogen-deficient carbon nitride (BNCN) and chlorin e6 (Ce6) can efficiently and selectively oxidize glucose into gluconic acid and glucaric acid. Introducing nitrogen defects could significantly enhance the optical absorption and modulate the band structure. In addition, the combination of Ce6 with BNCN further improve the optical absorption property and promote effective separation of photon-generated carriers. As expected, the resultant Ce6@BNCN catalyst gave a total selectivity of gluconic acid, glucaric acid and arabinose as high as 70.9% at glucose conversion up to 62.3%, as is superior to previously reported photocatalytic systems. The mechanism for the enhancement of catalytic performance and the reaction pathway were revealed by experimental studies combined with DFT calculations.
研究领域:
化学
·
材料科学
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催化
·
可持续化学
✓ 已验证
产品关联
DOI
高影响因子
CARBOHYDRATE POLYMERS
·
2023
·
IF 11.2
Chendi Ding,Zhaoqing Shi,Meitong Ou,Yingbang Li,Li Huang,Wenyan Wang,Qili Huang,Meihang Li,Chunbo Chen,Xiaowei Zeng,Hongzhong Chen,Lin Mei
Natural polysaccharides , represented by dextran , chitosan, and hyaluronic acid , are widely approved for use as pharmaceutical excipients and are important carrier materials for the design of advanced drug delivery systems, particularly in the field of anticancer drug delivery. The combination of stimuli-activable prodrug based chemotherapy and photodynamic therapy (PDT) has attracted increasing attention. Recent studies have verified the effectiveness of this strategy in the treatment of multiple aggressive cancers. However, in such combination, the stimuli-responsive chemotherapy and PDT have their own problems that need to be overcome. The uneven distribution of endogenous stimuli within tumor tissues makes it difficult for prodrug to be completely activated. And the inadequate tissue penetration depth of external light results in low efficiency of PDT. Aiming at these two bottlenecks, we designed a biocompatible dextran based - multi-component nanomedicine (PCL-NPs) that integrate a chemiluminescence agent luminol, a photosensitizer chlorine e6 (Ce6), and a reactive oxygen species (ROS)-activable thioketal-based paclitaxel (PTX) prodrug. The presence of overexpressed hydrogen peroxide (H 2 O 2 ) inside tumor oxidizes the luminol moiety to generate in-situ light for PDT through chemiluminescence resonance energy transfer (CRET). The singlet oxygen ( 1 O 2 ) produced in this process not only directly kills tumor cells but also amplifies oxidative stress to accelerate the activation of PTX prodrug. We propose that the PCL-NPs have great therapeutic potential by simultaneously enhancing chemotherapy and PDT in a combination therapy.
研究领域:
药学
·
癌症治疗
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纳米技术
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-16
·
IF 10.6
Fang Yujia,Yang Jianjun,Liang Xiayi,Wu Jing,Xie Mengqing,Zhang Kun,Su Chunxia
Reactive oxygen species (ROS)-associated anticancer approaches usually suffer from two limitations, i.e., insufficient ROS level and short ROS half-life. Nevertheless, no report has synchronously addressed both concerns yet. Herein, a multichannel actions-enabled nanotherapeutic platform using hollow manganese dioxide (H-MnO 2 ) carriers to load chlorin e6 (Ce6) sonosensitizer and CO donor (e.g., Mn 2 (CO) 10 ) has been constructed to maximumly elevate ROS level and trigger cascade catalysis to produce CO. Therein, intratumoral H 2 O 2 and ultrasound as endogenous and exogeneous triggers stimulate H-MnO 2 and Ce6 to produce •OH and 1 O 2 , respectively. The further cascade reaction between ROS and Mn 2 (CO) 10 proceeds to release CO, converting short-lived ROS into long-lived CO. Contributed by them, such a maximumly-elevated ROS accumulation and long-lived CO release successfully suppresses the progression, recurrence and metastasis of lung cancer with a prolonged survival rate. More significantly, proteomic and genomic investigations uncover that the CO-induced activation of AKT signaling pathway, NRF-2 phosphorylation and HMOX-1 overexpression induce mitochondrial dysfunction to boost anti-tumor consequences. Thus, this cascade catalysis strategy can behave as a general means to enrich ROS and trigger CO release against refractory cancers. Graphic Abstract
研究领域:
癌症生物学
·
药理学
·
纳米技术
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2024
·
IF 6.6
Hongwei Xiang,Bin Shen,Chunmei Zhang,Rui Li
Introduction Cell death regulation holds a unique value in the field of cancer therapy. Recently, disulfidptosis has garnered substantial scientific attention. Previous studies have reported that sonodynamic therapy (SDT) based on reactive oxygen species (ROS) can regulate cancer cell death, achieving an limited anti-cancer effect. However, the integration of SDT with disulfidptosis as an anti-cancer strategy has not been extensively developed. In this study, we constructed an artificial membrane disulfidptosis sonosensitizer, specifically, a nanoliposome (SC@lip) coated with a combination of the chemotherapy medicine Sorafenib (Sora) and sonosensitizer Chlorin e6 (Ce6), to realize a one-stop enhanced SDT effect that induces disulfidptosis-like cancer cell death.Methods Sorafenib and Ce6 were co-encapsulated into PEG-modified liposomes, and SC@Lip was constructed using a simple rotary evaporation phacoemulsification method. The cell phagocytosis, ROS generation ability, glutathione (GSH) depletion ability, lipid peroxidation (LPO), and disulfidptosis-like death mediated by SC@Lip under ultrasound (US) irradiation were evaluated. Based on a 4T1 subcutaneous tumor model, both the in vivo biological safety assessment and the efficacy of SDT were assessed.Results SC@Lip exhibits high efficiency in cellular phagocytosis. After being endocytosed by 4T1 cells, abundant ROS were produced under SDT activation, and the cell survival rates were below 5%. When applied to a 4T1 subcutaneous tumor model, the enhanced SDT mediated by SC@Lip inhibited tumor growth and prolonged the survival time of mice. In vitro and in vivo experiments show that SC@Lip can enhance the SDT effect and trigger disulfidptosis-like cancer cell death, thus achieving anti-tumor efficacy both in vitro and in vivo.Conclusion SC@Lip is a multifunctional nanoplatform with an artificial membrane, which can integrate the functions of sonosensitization and GSH depletion into a biocompatible nanoplatform, and can be used to enhance the SDT effect and promote disulfidptosis-like cancer cell death.
研究领域:
癌症治疗
·
纳米技术
·
细胞生物学
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药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2023
·
IF 13.3
Yang Zhou,Yiwei Zhang,Chaoqing Jiang,Yuxiu Chen,Fan Tong,Xiaotong Yang,Yazhen Wang,Xue Xia,Huile Gao
A primary concern about photodynamic therapy (PDT) is its inability to regulate the generation levels of reactive oxidative species (ROS) based on the complex microenvironment, resulting in the impairment toward normal tissues and immunosuppression. Besides, tumor metastasis also compromises PDT's efficacy and drives mortality. However, it is very challenging to achieve such two goals within one nanosystem. Here, the nanoassembly (CPR) with self-regulated photodynamic and antimetastasis properties comprises three parts: chlorin e6-conjugated β-cyclodextrin (CD-Ce6) acts as the main PDT agent and ferrocene (Fc)-terminated phenylboronic acid-containing conjugates entering into the cavity of CD-Ce6, as well as rosmarinic acid (RA)–boronic acid crosslinked shell. Compared with non-crosslinked counterpart, CPR displays better stability and enhanced tumor accumulation. Under laser irradiation, CPR generates plenty of ROS to damage tumor cells and induce immunogenic cell death. Mildly acidic TME partly cleaves the crosslinkers to dissociate antioxidant RAs from micelles, which together with Fc in CPR scavenge PDT-induced ROS in the TME. By contrast, under acidic lysosomal conditions, Fc catalyzes abundant H 2 O 2 in tumor cells to produce highly cytotoxic •OH, while RA continuously reduces ferroptosis-generated Fc + into Fc, both to augment the PDT efficacy in tumor cells. CPR also remarkably hinders the epithelial-mesenchymal transition to prevent the lung metastasis.
研究领域:
纳米技术
·
癌症研究
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG TARGETING
·
2021
·
IF 5.121
Xiangtian Deng,Qingcheng Song,Yiran Zhang,Weijian Liu,Hongzhi Hu,Yingze Zhang
Background Existing therapeutic efficacy of chemotherapy and photodynamic therapy (PDT) is always affected by some resistance factors from tumour environment (TME), such as hypoxia and the antioxidant defense system.Purpose This study aims at developing a cascaded intelligent multifunctional nanoplatforms to modulate the TME resistance for synergistically enhanced chemo- and photodynamic therapies.Methods In this study, we synthesised hollow manganese dioxide nanoparticles (HMDNs) loaded with the hydrophilic chemotherapeutic drug (acriflavine, ACF) and the hydrophobic photosensitizer (chlorine6, Ce6), which was further encapsulated by pH-sensitive liposome to form core-shell nanocomposite, with surface modified with arginine-glycine-aspartic acid (RGD) peptide to achieve tumour targeting.Results After uptake by tumour cells, the liposome shell was rapidly degraded by the low pH, and the inner core could be released from the liposome. Then, the released HMDNs/ACF/Ce6 would be dissociated by low pH and high levels of intracellular GSH within TME to release encapsulated drugs, thereby resulting in synergistic effects of chemotherapy and PDT. Meanwhile, the released ACF could bind with HIF-1a and then inhibit the expression levels of HIF-1’s downstream signalling molecules P-gp and VEGF, which could further strengthen the antitumor effects. As a result, HMDNs/ACF/Ce6@Lipo-RGD NPs with laser irradiation exhibited superior anti-tumour therapeutic efficiency.
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
Advanced Healthcare Materials
·
2020
·Vol. 9
·期 21
·1901634
·
IF 7.367
Baochan Yang,Zhichao Dai,Gaorui Zhang,Zunfu Hu,Xiuxiu Yao,Shan Wang,Qingyun Liu,Xiuwen Zheng
Multimodal imaging-guided synergistic anticancer strategies have attracted increasing attention for efficient diagnosis and therapy of cancer. Herein, a multifunctional nanotheranostic agent FePtMn-Ce6/FA (FPMCF NPs) is constructed by covalently anchoring photosensitizer chlorin e6 (Ce6) and targeting molecule folic acid (FA) on ultrasmall homogeneous ternary FePtMn nanocrystals. Response to tumor microenvironment (TME), FPMCF NPs can release Fe 2+ to catalyze H 2 O 2 into •OH by Fenton reaction and simultaneously catalyze hydrogen peroxide (H 2 O 2 ) into O 2 to overcome the tumor hypoxia barrier. Released O 2 is further catalyzed into 1 O 2 under 660 nm laser irradiation with Ce6. Thus, the FPMCF NPs exhibit superior dual-ROS oxidization capability including ferroptosis chemodynamic oxidization and 1 O 2 -based photodynamic oxidization. Interestingly, FPMCF NPs reveal strong photothermal conversion efficiency exposed to an 808 nm laser, which can assist dual-ROS oxidization to suppress solid tumor remarkably. Additionally, Mn 2+ can be released from FPMCF NPs to enhance longitudinal relaxivity (T 1 -weighted magnetic resonance (MR) imaging) and Fe-synergistic transverse relaxivity (T 2 -weighted MR imaging), which is convenient for diagnosis of solid tumors. Meanwhile, the fluorescent/photothermal (FL/PT) imaging function of FPMCF NPs can also accurately monitor tumor location. Therefore, FPMCF NPs with multimodal MR/FL/PT imaging-guided synergistic chemodynamic/photodynamic/photothermal cancer therapy capability have potential bioapplication in bionanomedicine field.
研究领域:
纳米技术
·
癌症治疗
·
生物医学工程
·
材料科学
·
成像技术
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）