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Journal ArticleDOI: 10.1039/D0CC08162K

A two-pronged photodynamic nanodrug to prevent metastasis of basal-like breast cancer.

02 Mar 2021-Chemical Communications (The Royal Society of Chemistry)-Vol. 57, Iss: 18, pp 2305-2308
Abstract: A two-pronged concept combining photodynamic therapy (PDT) and epithelial-mesenchymal transition (EMT) blockade in a minimalist nanoplatform was proposed to combat basal-like breast cancer (BLBC) metastasis. Based on PDT-mediated tumor killing and epalrestat (Epa)-mediated EMT blockade, as-prepared Ce6/Epa nanoparticles prevented BLBC metastasis effectively in vivo, providing a very promising two-pronged strategy against BLBC metastasis.

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Topics: Metastasis (52%)

23 results found

Journal ArticleDOI: 10.1016/J.JIEC.2021.04.016
Seul Gi Kim1, Akhmad Irhas Robby1, Byung-Chan Lee1, Gibaek Lee1  +1 moreInstitutions (1)
Abstract: Enhancing therapeutic efficacy of drugs from reactive oxygen species (ROS) and glutathione (GSH)-responsive matrix and minimizing toxic effects on normal cells remains a challenge in programmable anticancer drug delivery. Herein, ROS- and GSH-responsive paclitaxel (PTX)-loaded polymer dot (PD) with mitochondria-targeting capability was designed by constructing diselenide linkage and triphenylphosphonium (TPP) for tunable PTX release and fluorescence for cancer theranostics. PD-TPP nanocarrier could improve the PTX stability after loading (PD-TPP(PTX)), and the cleavage of diselenide bond in the presence of H2O2 and GSH triggered the controllable PTX release, providing higher fluorescence intensity. As the levels of H2O2 and GSH are higher in cancer cells compared to normal cells, PTX was selectively released from PD-TPP in cancer cells, reducing cell viability (∼25%) and causing enhanced apoptosis of cancer cells compared to normal cells. The PD-TPP(PTX) selectivity was also reflected by distinct fluorescence intensity in HeLa and PC-3 cells (cancer) compared to CHO-K1 cells (normal). Furthermore, conjugated TPP promoted the PD-TPP(PTX) accumulation in mitochondria due to specific targeting of TPP towards mitochondria, allowing PTX release in mitochondria of cancer cells. Hence, this approach could be a potential strategy to enhance therapeutic efficacy of cancer drugs and minimize the side effects on normal cells.

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Topics: Cancer cell (53%), HeLa (50%)

12 Citations

Open accessJournal ArticleDOI: 10.1016/J.BIOACTMAT.2021.05.030
Jie Yu1, Jie Yu2, Sha Liu1, Yupeng Wang1  +11 moreInstitutions (3)
Abstract: The combination of tumor ablation and immunotherapy is a promising strategy against tumor relapse and metastasis. Photothermal therapy (PTT) triggers the release of tumor-specific antigens and damage associated molecular patterns (DAMPs) in-situ. However, the immunosuppressive tumor microenvironment restrains the activity of the effector immune cells. Therefore, systematic immunomodulation is critical to stimulate the tumor microenvironment and augment the anti-tumor therapeutic effect. To this end, polyethylene glycol (PEG)-stabilized platinum (Pt) nanoparticles (Pt NPs) conjugated with a PD-L1 inhibitor (BMS-1) through a thermo-sensitive linkage were constructed. Upon near-infrared (NIR) exposure, BMS-1 was released and maleimide (Mal) was exposed on the surface of Pt NPs, which captured the antigens released from the ablated tumor cells, resulting in the enhanced antigen internalization and presentation. In addition, the Pt NPs acted as immune adjuvants by stimulating dendritic cells (DCs) maturation. Furthermore, BMS-1 relieved T cell exhaustion and induced the infiltration of effector T cells into the tumor tissues. Thus, Pt NPs can ablate tumors through PTT, and augment the anti-tumor immune response through enhanced antigen presentation and T cells infiltration, thereby preventing tumor relapse and metastasis.

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Topics: Tumor microenvironment (56%), T cell (54%), Antigen presentation (54%) ... read more

4 Citations

Journal ArticleDOI: 10.1016/J.MOLLIQ.2021.116327
Iqra Munir1, Mehvish Perveen1, Sidra Nazir, Rasheed Ahmad Khera1  +3 moreInstitutions (1)
Abstract: In this research, for the first time; graphyne is investigated as a carrier for delivery of anticancer drug, daunorubicin. The effectiveness of graphyne as a carrier, is explored with the help of calculations of some physiochemical properties such as band-gap, dipole-moment, and chemical-reactivity-descriptors for daunorubicin drug, graphyne carrier and daunorubicin-graphyne complex by using Density Functional Theory (DFT) method. Daunorubicin has significant antimitotic and cytotoxic activity as it can form complex with DNA by intercalation. The nature of interactions between graphyne and daunorubicin complex are clarified through noncovalent-interaction (NCI) analysis, which demonstrated that Vander-Waals force of interactions are present between the graphyne carrier molecule and daunorubicin drug. Daunorubicin drug will easily off-load at the target point as weak forces are present between drug and graphyne carrier. Frontier-molecular-orbital-analysis explained that how charge-transferred from daunorubicin to graphyne in complex formation process. The charge-transfer process is further studied by charge-decomposition-analysis (CDA). The calculations at excited-state indicated that the λmax of daunorubicin-graphyne complex show red-shift of 91 nm. PET process is also studied for excited-states of daunorubicin-graphyne complex with the help of electron-hole theory and it revealed that fluorescence-quenching process will occur in complex molecule. The process of fluorescence-detection is very useful for systematic delivery of daunorubicin drug at target site for the perfect treatment. Moreover, the effect of + 1 and −1 charge-state on graphyne molecule and its complex with daunorubicin is also investigated. Overall, the calculations suggested that graphyne could be utilized as an efficient carrier for targeted-delivery of daunorubicin.

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Topics: Graphyne (62%), Daunorubicin (55%)

3 Citations

Open accessJournal ArticleDOI: 10.1021/ACSOMEGA.1C03816
13 Sep 2021-
Abstract: pH-sensitive nanocarriers can effectively deliver anticancer drugs to tumors and reduce the adverse effects of conventional chemotherapy. In this light, we prepared a novel pH-responsive deferasirox (DFX)-loaded vesicle and comprehensively performed in silico, in vitro, and in vivo studies to examine the properties of the newly synthesized formulation. Physiochemical assessment of the developed formulations showed that they have an average size (107 ± 2 nm), negative zeta potential (-29.1 ± 1.5 mV), high encapsulation efficiency (84.2 ± 2.6%), and a pH-responsive release. Using the molecular dynamics simulation, the structural and dynamic properties of ergosterol-containing niosomes (ST60/Ergo) in the presence of DFX molecules were analyzed and showed a good interaction between DFX and vesicle components. Cytotoxic assessment showed that niosomal DFX exhibited a greater cytotoxic effect than free DFX in both human cancer cells (MCF-breast cancer and Hela cervical cancer) and induced evident morphological features of apoptotic cell death. No marked difference between the ability of free and niosomal DFX was found in activating caspase-3 in Hela cells. Eight weeks of intraperitoneal administrations of free DFX at three doses caused a significant increase in serum biochemical parameters and liver lipid peroxidation. Treatment with 5 mg/kg dose of niosomal DFX caused a significant increase in serum creatinine (P < 0.05); however, other parameters remained unchanged. On the other hand, administration of niosomal DFX at the highest dose (10 mg/kg) significantly increased serum creatinine (P < 0.05), BUN, and serum liver enzymes compared to the control rats (P < 0.001). Based on the results, the application of pH-responsive DFX-loaded niosomes, as a novel drug delivery platform, may yield promising results in cancer treatment.

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2 Citations


20 results found

Open accessJournal ArticleDOI: 10.3322/CAAC.21492
Abstract: This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions There will be an estimated 181 million new cancer cases (170 million excluding nonmelanoma skin cancer) and 96 million cancer deaths (95 million excluding nonmelanoma skin cancer) in 2018 In both sexes combined, lung cancer is the most commonly diagnosed cancer (116% of the total cases) and the leading cause of cancer death (184% of the total cancer deaths), closely followed by female breast cancer (116%), prostate cancer (71%), and colorectal cancer (61%) for incidence and colorectal cancer (92%), stomach cancer (82%), and liver cancer (82%) for mortality Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality) Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts CA: A Cancer Journal for Clinicians 2018;0:1-31 © 2018 American Cancer Society

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Topics: Cancer registry (78%), Cancer (72%), Breast cancer (63%) ... read more

39,828 Citations

Journal ArticleDOI: 10.1038/NRC2620
Kornelia Polyak1, Robert A. Weinberg2Institutions (2)
Abstract: Transitions between epithelial and mesenchymal states have crucial roles in embryonic development. Emerging data suggest a role for these processes in regulating cellular plasticity in normal adult tissues and in tumours, where they can generate multiple, distinct cellular subpopulations contributing to intratumoural heterogeneity. Some of these subpopulations may exhibit more differentiated features, whereas others have characteristics of stem cells. Owing to the importance of these tumour-associated phenotypes in metastasis and cancer-related mortality, targeting the products of such cellular plasticity is an attractive but challenging approach that is likely to lead to improved clinical management of cancer patients.

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Topics: Stem cell (54%), Mesenchymal stem cell (51%)

2,896 Citations

Open accessJournal ArticleDOI: 10.1101/GAD.225334.113
Jeff H. Tsai, Jing Yang1Institutions (1)
Abstract: Tumor metastasis is a multistep process by which tumor cells disseminate from their primary site and form secondary tumors at a distant site. Metastasis occurs through a series of steps: local invasion, intravasation, transport, extravasation, and colonization. A developmental program termed epithelial-mesenchymal transition (EMT) has been shown to play a critical role in promoting metastasis in epithelium-derived carcinoma. Recent experimental and clinical studies have improved our knowledge of this dynamic program and implicated EMT and its reverse program, mesenchymal-epithelial transition (MET), in the metastatic process. Here, we review the functional requirement of EMT and/or MET during the individual steps of tumor metastasis and discuss the potential of targeting this program when treating metastatic diseases.

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888 Citations

Open accessJournal ArticleDOI: 10.1016/S0140-6736(07)60781-8
Suzanne A. Eccles, Danny R. Welch1Institutions (1)
19 May 2007-The Lancet
Abstract: Most cancer deaths are due to the development of metastases, hence the most important improvements in morbidity and mortality will result from prevention (or elimination) of such disseminated disease. Some would argue that treatments directed against metastasis are too late because cells have already escaped from the primary tumour. Such an assertion runs contrary to the significant but (for many common adult cancers) fairly modest improvements in survival following the use of adjuvant radiation and chemotherapy designed to eliminate disseminated cells after surgical removal of the primary tumour. Nonetheless, the debate raises important issues concerning the accurate early identification of clonogenic, metastatic cells, the discovery of novel, tractable targets for therapy, and the monitoring of minimal residual disease. We focus on recent findings regarding intrinsic and extrinsic molecular mechanisms controlling metastasis that determine how, when, and where cancers metastasise, and their implications for patient management in the 21st century.

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Topics: Metastasis (50%)

618 Citations

Open accessJournal ArticleDOI: 10.1186/BCR1771
Abstract: Introduction Breast cancer is a heterogeneous group of tumors, and can be subdivided on the basis of histopathological features, genetic alterations and gene-expression profiles One well-defined subtype of breast cancer is characterized by a lack of HER2 gene amplification and estrogen and progesterone receptor expression ('triple-negative tumors') We examined the histopathological and gene-expression profile of triple-negative tumors to define subgroups with specific characteristics, including risk of developing distant metastases

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Topics: Breast cancer (58%), Progesterone receptor (52%), Surgical oncology (52%) ... read more

562 Citations