Enhancement of mitochondrial ROS accumulation and radiotherapeutic efficacy using a Gd-doped titania nanosensitizer.


:Radiotherapy is an extensively used treatment modality in the clinic and can kill malignant cells by generating cytotoxic reactive oxygen species (ROS). Unfortunately, excessive dosages of radiation are typically required because only a small proportion of the radiative energy is adsorbed by the soft tissues of a tumor, which results in the nonselective killing of normal cells and severe systemic side effects. An efficient nanosensitizer that makes cancer cells more sensitive to radiotherapy under a relatively low radiation dose would be highly desirable. Methods: In this study, we developed a Gd-doped titania nanosensitizer that targets mitochondria to achieve efficient radiotherapy. Upon X-ray irradiation, the nanosensitizer triggers a "domino effect" of ROS accumulation in mitochondria. This overabundance of ROS leads to mitochondrial permeability transition and ultimately irreversible cell apoptosis. Confocal laser imaging, western blotting and flow cytometry analysis were used to explore the biological process of intrinsic apoptosis induced by the nanosensitizer. Clonogenic survival assay, cell migration and invasion experiments were employed to evaluate the radiosensitizing effect of the nanosensitizer in vitro. Finally, to evaluate the therapeutic outcome of the nanosensitizer in vivo, MCF-7 tumor model was used. Results: Confocal laser images and western blotting data demonstrated that the nanosensitizer in conjunction with X-ray irradiation could induce cell apoptosis in ROS-mediated apoptotic signal pathways. A clonogenic survival assay revealed that cells treated with the prepared nanosensitizer exhibited a lower number of viable cell colonies than that of the nontargeted group under X-ray irradiation. Notably, with only a single dose of radiotherapy, the mitochondria-targeted nanosensitizer elicited the complete ablation of tumors in a mouse model. Conclusion: The designed nanosensitizer in combination with X-ray radiation exposure could be used for radiotherapy against cancer in living cells and in vivo. Moreover, the nanosensitizer with mitochondria targeting played a pivotal role in triggering a "domino effect" of ROS and cell apoptosis. The current strategy could provide new opportunities in designing efficient radiosensitizers for future cancer therapy.






Chen Y,Li N,Wang J,Zhang X,Pan W,Yu L,Tang B




Has Abstract


2019-01-01 00:00:00












  • Phototherapy-based combination strategies for bacterial infection treatment.

    abstract::The development of nanomedicine is expected to provide an innovative direction for addressing challenges associated with multidrug-resistant (MDR) bacteria. In the past decades, although nanotechnology-based phototherapy has been developed for antimicrobial treatment since it rarely causes bacterial resistance, the cl...


    pub_type: 杂志文章,评审


    authors: Wei G,Yang G,Wang Y,Jiang H,Fu Y,Yue G,Ju R

    更新日期:2020-10-30 00:00:00

  • CDK4/6 inhibition promotes immune infiltration in ovarian cancer and synergizes with PD-1 blockade in a B cell-dependent manner.

    abstract::Great progress has been made in the field of tumor immunotherapy in the past decade. However, the therapeutic effects of immune checkpoint blockade (ICB) against ovarian cancer are still limited. Recently, an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6i) has been reported to enhance antitumor immunity in pre...


    pub_type: 杂志文章


    authors: Zhang QF,Li J,Jiang K,Wang R,Ge JL,Yang H,Liu SJ,Jia LT,Wang L,Chen BL

    更新日期:2020-08-25 00:00:00

  • PLAGL2 promotes the proliferation and migration of gastric cancer cells via USP37-mediated deubiquitination of Snail1.

    abstract::Rationale: PLAGL2 (pleomorphic adenoma gene like-2), a zinc finger PLAG transcription factor, is aberrantly expressed in several malignant tumors. However, the biological roles of PLAGL2 and its underlying mechanism in gastric cancer (GC) remain unclear. Methods: A series of experiments in vitro and in vivo were condu...


    pub_type: 杂志文章


    authors: Wu L,Zhao N,Zhou Z,Chen J,Han S,Zhang X,Bao H,Yuan W,Shu X

    更新日期:2021-01-01 00:00:00

  • Pre-existing anti-polyethylene glycol antibody reduces the therapeutic efficacy and pharmacokinetics of PEGylated liposomes.

    abstract::Rationale: Increasing frequency of human exposure to PEG-related products means that healthy people are likely to have pre-existing anti-PEG antibodies (pre-αPEG Ab). However, the influence of pre-αPEG Abs on the pharmacokinetics (PK) and therapeutic efficacy of LipoDox is unknown. Methods: We generated two pre-αPEG A...


    pub_type: 杂志文章


    authors: Hsieh YC,Wang HE,Lin WW,Roffler SR,Cheng TC,Su YC,Li JJ,Chen CC,Huang CH,Chen BM,Wang JY,Cheng TL,Chen FM

    更新日期:2018-05-09 00:00:00

  • Multicolor upconversion nanoparticles for protein conjugation.

    abstract::We describe the preparation of monodisperse, lanthanide-doped hexagonal-phase NaYF4 upconverting luminescent nanoparticles for protein conjugation. Their core was coated with a silica shell which then was modified with a poly(ethylene glycol) spacer and N-hydroxysuccinimide ester groups. The nanoparticles were charact...


    pub_type: 杂志文章


    authors: Wilhelm S,Hirsch T,Patterson WM,Scheucher E,Mayr T,Wolfbeis OS

    更新日期:2013-03-13 00:00:00

  • Self-assembly of porphyrin-grafted lipid into nanoparticles encapsulating doxorubicin for synergistic chemo-photodynamic therapy and fluorescence imaging.

    abstract::The limited clinical efficacy of monotherapies in the clinic has urged the development of novel combination platforms. Taking advantage of light-triggered photodynamic treatment combined together with the controlled release of nanomedicine, it has been possible to treat cancer without eliciting any adverse effects. Ho...


    pub_type: 杂志文章


    authors: Hameed S,Bhattarai P,Liang X,Zhang N,Xu Y,Chen M,Dai Z

    更新日期:2018-11-03 00:00:00

  • circPTCH1 promotes invasion and metastasis in renal cell carcinoma via regulating miR-485-5p/MMP14 axis.

    abstract::Background: Circular RNAs (circRNAs) are a new class of non-coding RNAs (ncRNAs) that are derived from exons or introns by special selective shearing. circRNAs have been shown to play critical roles in various human cancers. However, their roles in renal cell carcinoma (RCC) and the underlying mechanisms remain largel...


    pub_type: 杂志文章


    authors: Liu H,Hu G,Wang Z,Liu Q,Zhang J,Chen Y,Huang Y,Xue W,Xu Y,Zhai W

    更新日期:2020-08-29 00:00:00

  • Noninvasive application of mesenchymal stem cell spheres derived from hESC accelerates wound healing in a CXCL12-CXCR4 axis-dependent manner.

    abstract::Mesenchymal stem cells (MSC) derived from adult tissues effectively promote wound healing. However, MSC quality varies, and the quantity of MSC is limited, as MSC are acquired through donations. Moreover, the survival and functioning of dissociated MSC delivered to an inflammatory lesion are subject to challenges. Met...


    pub_type: 杂志文章


    authors: Wang X,Jiang B,Sun H,Zheng D,Zhang Z,Yan L,Li E,Wu Y,Xu RH

    更新日期:2019-08-14 00:00:00

  • Recent Progress in Light-Triggered Nanotheranostics for Cancer Treatment.

    abstract::Treatments of high specificity are desirable for cancer therapy. Light-triggered nanotheranostics (LTN) mediated cancer therapy could be one such treatment, as they make it possible to visualize and treat the tumor specifically in a light-controlled manner with a single injection. Because of their great potential in c...


    pub_type: 杂志文章,评审


    authors: Zhang P,Hu C,Ran W,Meng J,Yin Q,Li Y

    更新日期:2016-04-27 00:00:00

  • PET Tracer 18F-Fluciclovine Can Detect Histologically Proven Bone Metastatic Lesions: A Preclinical Study in Rat Osteolytic and Osteoblastic Bone Metastasis Models.

    abstract::18F-Fluciclovine (trans-1-amino-3-18F-fluorocyclobutanecarboxylic acid; anti-18F-FACBC) is a positron emission tomography (PET) tracer for diagnosing cancers (e.g., prostate and breast cancer). The most frequent metastatic organ of these cancers is bone. Fluciclovine-PET can visualize bony lesions in clinical practice...


    pub_type: 杂志文章


    authors: Oka S,Kanagawa M,Doi Y,Schuster DM,Goodman MM,Yoshimura H

    更新日期:2017-05-15 00:00:00

  • Nanotopography-based lymphatic delivery for improved anti-tumor responses to checkpoint blockade immunotherapy.

    abstract::Rationale: Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is a co-inhibitory checkpoint receptor that is expressed by naïve T-cells in lymph nodes (LNs) to inhibit activation against "self" antigens (Ags). In cancer, anti-CTLA-4 blocks inhibitory action, enabling robust activation of T-cells against tumor Ags pr...


    pub_type: 杂志文章


    authors: Kwon S,Velasquez FC,Rasmussen JC,Greives MR,Turner KD,Morrow JR,Hwu WJ,Ross RF,Zhang S,Sevick-Muraca EM

    更新日期:2019-10-22 00:00:00

  • Signal amplification and quantification on lateral flow assays by laser excitation of plasmonic nanomaterials.

    abstract::Lateral flow assay (LFA) has become one of the most widely used point-of-care diagnostic methods due to its simplicity and low cost. While easy to use, LFA suffers from its low sensitivity and poor quantification, which largely limits its applications for early disease diagnosis and requires further testing to elimina...


    pub_type: 杂志文章,评审


    authors: Ye H,Liu Y,Zhan L,Liu Y,Qin Z

    更新日期:2020-03-15 00:00:00

  • ROS-Responsive Mitochondria-Targeting Blended Nanoparticles: Chemo- and Photodynamic Synergistic Therapy for Lung Cancer with On-Demand Drug Release upon Irradiation with a Single Light Source.

    abstract::Mitochondria in cancer cells maintain a more negative membrane potential than normal cells. Mitochondria are the primary source of cellular reactive oxygen species (ROS), which are necessary for photodynamic therapy. Thus, the strategy of targeting mitochondria can maximize the photodynamic therapeutic efficiency for ...


    pub_type: 杂志文章


    authors: Yue C,Yang Y,Zhang C,Alfranca G,Cheng S,Ma L,Liu Y,Zhi X,Ni J,Jiang W,Song J,de la Fuente JM,Cui D

    更新日期:2016-10-01 00:00:00

  • MMPP Attenuates Non-Small Cell Lung Cancer Growth by Inhibiting the STAT3 DNA-Binding Activity via Direct Binding to the STAT3 DNA-Binding Domain.

    abstract::Rationale: Signal transducer and activator of transcription-3 (STAT3) plays a pivotal role in cancer biology. Many small-molecule inhibitors that target STAT3 have been developed as potential anticancer drugs. While designing small-molecule inhibitors that target the SH2 domain of STAT3 remains the leading focus for d...


    pub_type: 杂志文章


    authors: Son DJ,Zheng J,Jung YY,Hwang CJ,Lee HP,Woo JR,Baek SY,Ham YW,Kang MW,Shong M,Kweon GR,Song MJ,Jung JK,Han SB,Kim BY,Yoon DY,Choi BY,Hong JT

    更新日期:2017-10-16 00:00:00

  • LPA3-mediated lysophosphatidic acid signaling promotes postnatal heart regeneration in mice.

    abstract::Background: Lysophosphatidic acid (LPA) is a small glycerophospholipid that acts as a potent extracellular signal in various biological processes and diseases. Our previous work demonstrated that the expression of the LPA receptors LPA1 and LPA3 is elevated in the early postnatal heart. However, the role of this stage...


    pub_type: 杂志文章


    authors: Wang F,Liu S,Pei J,Cai L,Liu N,Liang T,Dong X,Cong X,Chun J,Chen J,Hu S,Chen X

    更新日期:2020-08-29 00:00:00

  • Lipid- and polymer-based nanostructures for cancer theranostics.

    abstract::The relatively new field of nanotheranostics combines the advantages of in vivo diagnosis with the ability to administer treatment through a single nano-sized carrier, offering new opportunities for cancer diagnosis and therapy. Nanotheranostics has facilitated the development of nanomedicine through direct visualizat...


    pub_type: 杂志文章,评审


    authors: Luk BT,Fang RH,Zhang L

    更新日期:2012-01-01 00:00:00

  • Visualizing Autophagic Flux during Endothelial Injury with a Pathway-Inspired Tandem-Reaction Based Fluorogenic Probe.

    abstract::Autophagy is a dynamic and complicated catabolic process. Imaging autophagic flux can clearly advance knowledge of its pathophysiology significance. While the most common way autophagy is imaged relies on fluorescent protein-based probes, this method requires substantial genetic manipulation that severely restricts th...


    pub_type: 杂志文章


    authors: Lei Y,Ren W,Wang CK,Tao RR,Xiang HJ,Feng LL,Gao YP,Jiang Q,Li X,Hu Y,Han F

    更新日期:2019-08-01 00:00:00

  • Absence of Interferon Regulatory Factor 1 Protects Against Atherosclerosis in Apolipoprotein E-Deficient Mice.

    abstract::Deciphering the molecular and cellular processes involved in foam cell formation is critical to understanding the pathogenesis of atherosclerosis. Interferon regulatory factor 1 (IRF1) was first identified as a transcriptional regulator of type-I interferons (IFNs) and IFN inducible genes. Our study aims to explore th...


    pub_type: 杂志文章


    authors: Du M,Wang X,Mao X,Yang L,Huang K,Zhang F,Wang Y,Luo X,Wang C,Peng J,Liang M,Huang D,Huang K

    更新日期:2019-07-09 00:00:00

  • Breaking the Barrier - Potent Anti-Inflammatory Activity following Efficient Topical Delivery of Etanercept using Thermoresponsive Nanogels.

    abstract::Topical administration permits targeted, sustained delivery of therapeutics to human skin. Delivery to the skin, however, is typically limited to lipophilic molecules with molecular weight of < 500 Da, capable of crossing the stratum corneum. Nevertheless, there are indications protein delivery may be possible in barr...


    pub_type: 杂志文章


    authors: Giulbudagian M,Yealland G,Hönzke S,Edlich A,Geisendörfer B,Kleuser B,Hedtrich S,Calderón M

    更新日期:2018-01-01 00:00:00

  • PI3K-AKT-mTOR-signaling and beyond: the complex network in gastroenteropancreatic neuroendocrine neoplasms.

    abstract::Gastroenteropancreatic neuroendocrine neoplasms are heterogeneous in their clinical behavior and require therapies specially tailored according to staging, grading, origin and expression of peptide receptors. Despite extensive scientific efforts, the therapy options are still not satisfactory. The main reasons are due...


    pub_type: 杂志文章,评审


    authors: Briest F,Grabowski P

    更新日期:2014-01-29 00:00:00

  • An Activatable Near-Infrared Chromophore for Multispectral Optoacoustic Imaging of Tumor Hypoxia and for Tumor Inhibition.

    abstract::Hypoxia is a key hallmark of solid tumors and tumor hypoxia usually contributes to cancer progression, therapeutic resistance and poor outcome. Accurately detecting and imaging tumor hypoxia with high spatial resolution would be conducive to formulating optimized treatment plan and thus achieving better patient outcom...


    pub_type: 杂志文章


    authors: Huang J,Wu Y,Zeng F,Wu S

    更新日期:2019-09-25 00:00:00

  • Coating Solid Lipid Nanoparticles with Hyaluronic Acid Enhances Antitumor Activity against Melanoma Stem-like Cells.

    abstract::Successful anticancer chemotherapy requires targeting tumors efficiently and further potential to eliminate cancer stem cell (CSC) subpopulations. Since CD44 is present on many types of CSCs, and it binds specially to hyaluronic acid (HA), we tested whether coating solid lipid nanoparticles with hyaluronan (HA-SLNs)wo...


    pub_type: 杂志文章


    authors: Shen H,Shi S,Zhang Z,Gong T,Sun X

    更新日期:2015-04-05 00:00:00

  • A new class of PentixaFor- and PentixaTher-based theranostic agents with enhanced CXCR4-targeting efficiency.

    abstract::Non-invasive PET imaging of CXCR4 expression in cancer and inflammation as well as CXCR4-targeted radioligand therapy (RLT) have recently found their way into clinical research by the development of the theranostic agents [68Ga]PentixaFor (cyclo(D-Tyr1-D-[NMe]Orn2(AMBS-[68Ga]DOTA)-Arg3-Nal4-Gly5) = [68Ga]DOTA-AMBS-CPC...


    pub_type: 杂志文章


    authors: Osl T,Schmidt A,Schwaiger M,Schottelius M,Wester HJ

    更新日期:2020-07-09 00:00:00

  • A Blood-Based Multi Marker Assay Supports the Differential Diagnosis of Early-Stage Pancreatic Cancer.

    abstract::The most frequent malignancy of the pancreas is the pancreatic ductal adenocarcinoma (PDAC). Despite many efforts PDAC has still a dismal prognosis. Biomarkers for early disease stage diagnosis as a prerequisite for a potentially curative treatment are still missing. Novel blood-based markers may help to overcome this...


    pub_type: 杂志文章


    authors: Berger AW,Schwerdel D,Reinacher-Schick A,Uhl W,Algül H,Friess H,Janssen KP,König A,Ghadimi M,Gallmeier E,Bartsch DK,Geissler M,Staib L,Tannapfel A,Kleger A,Beutel A,Schulte LA,Kornmann M,Ettrich TJ,Seufferlein T

    更新日期:2019-02-12 00:00:00

  • Lymphocytic subsets play distinct roles in heart diseases.

    abstract::Heart diseases are one of the leading causes of death for humans in the world. Increasing evidence has shown that myocardial injury induced innate and adaptive immune responses upon early cellular damage but also during chronic phases post-injury. The immune cells can not only aggravate the injury but also play an ess...


    pub_type: 杂志文章,评审


    authors: Wang J,Duan Y,Sluijter JP,Xiao J

    更新日期:2019-05-31 00:00:00

  • Type H blood vessels in bone modeling and remodeling.

    abstract::In the mammalian skeletal system, osteogenesis and angiogenesis are intimately linked during bone growth and regeneration in bone modeling and during bone homeostasis in bone remodeling. Recent studies have expanded our knowledge about the molecular and cellular mechanisms responsible for coupling angiogenesis and bon...


    pub_type: 杂志文章,评审


    authors: Peng Y,Wu S,Li Y,Crane JL

    更新日期:2020-01-01 00:00:00

  • Focused ultrasound as a novel strategy for noninvasive gene delivery to retinal Müller glia.

    abstract::Müller glia are specialized retinal cells with stem cell properties in fish and frogs but not in mammals. Current efforts to develop gene therapies to activate mammalian Müller glia for retinal repair will require safe and effective delivery strategies for recombinant adeno-associated viruses (AAVs), vectors of choice...


    pub_type: 杂志文章


    authors: Touahri Y,Dixit R,Kofoed RH,Miloska K,Park E,Raeisossadati R,Markham-Coultes K,David LA,Rijal H,Zhao J,Lynch M,Hynynen K,Aubert I,Schuurmans C

    更新日期:2020-02-10 00:00:00

  • Quantification of Tumor Vascular Permeability and Blood Volume by Positron Emission Tomography.

    abstract::Purpose: Evans Blue (EB) is an azo dye that binds quantitatively with serum albumin. With an albumin binding, NOTA conjugated truncated Evan's blue (NEB) dye derived PET tracer, we aimed to establish a strategy for evaluating vascular permeability in malignant tumors via non-invasive PET. Experimental design: Sixty-mi...


    pub_type: 杂志文章


    authors: Chen H,Tong X,Lang L,Jacobson O,Yung BC,Yang X,Bai R,Kiesewetter DO,Ma Y,Wu H,Niu G,Chen X

    更新日期:2017-06-14 00:00:00

  • Spontaneous evolution of human skin fibroblasts into wound-healing keratinocyte-like cells.

    abstract::Producing keratinocyte cells (KCs) in large scale is difficult due to their slow proliferation, disabling their use as seed cells for skin regeneration and wound healing. Cell reprogramming is a promising inducer-based approach to KC production but only reaches very low cellular conversion. Here we reported a unique c...


    pub_type: 杂志文章


    authors: Zhang F,Zhang D,Cheng K,Zhou Z,Liu S,Chen L,Hu Y,Mao C,Liu S

    更新日期:2019-07-09 00:00:00

  • Lentinan-functionalized Selenium Nanoparticles target Tumor Cell Mitochondria via TLR4/TRAF3/MFN1 pathway.

    abstract::Rationale: Malignant ascites caused by cancer cells results in poor prognosis and short average survival time. No effective treatment is currently available for malignant ascites. In this study, the effects of lentinan (LNT)-functionalized selenium nanoparticles (Selene) on malignant ascites were evaluated. Furthermor...


    pub_type: 杂志文章


    authors: Liu HJ,Qin Y,Zhao ZH,Zhang Y,Yang JH,Zhai DH,Cui F,Luo C,Lu MX,Liu PP,Xu HW,Li K,Sun B,Chen S,Zhou HG,Yang C,Sun T

    更新日期:2020-07-11 00:00:00