Repurposing Pentacyclic Triterpenoids as Ferroptosis Inducing Agents for Cancer Therapies

Encapsulation of synthesized purpurin-18-N-aminoimide methyl ester in lipid nanovesicles for use as agents in photodynamic cancer therapy.

Conjugated polymers (CPs) with strong near-infrared (NIR) absorption and high heat conversion efficiency have emerged as a new generation of photothermal therapy (PTT) agents for cancer therapy. An efficient strategy to design NIR absorbing CPs with good water dispersibility is essential to achieve excellent therapeutic effect. In this work, poly[9,9-bis(4-(2-ethylhexyl)phenyl)fluorene-alt-co-6,7-bis(4-(hexyloxy)phenyl)-4,9-di(thiophen-2-yl)-thiadiazoloquinoxaline] (PFTTQ) is synthesized through the combination of donor-acceptor moieties by Suzuki polymerization. PFTTQ nanoparticles (NPs) are fabricated through a precipitation approach using 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000 ) as the encapsulation matrix. Due to the large NIR absorption coefficient (3.6 L g(-1) cm(-1) ), the temperature of PFTTQ NP suspension (0.5 mg/mL) could be rapidly increased to more than 50 °C upon continuous 808 nm laser irradiation (0.75 W/cm(2) ) for 5 min. The PFTTQ NPs show good biocompatibility to both MDA-MB-231 cells and Hela cells at 400 μg/mL of NPs, while upon laser irradiation, effective cancer cell killing is observed at a NP concentration of 50 μg/mL. Moreover, PFTTQ NPs could efficiently ablate tumor in in vivo study using a Hela tumor mouse model. Considering the large amount of NIR absorbing CPs available, the general encapsulation strategy will enable the development of more efficient PTT agents for cancer or tumor therapy.

Topoisomerase (Topo) inhibitors have long been known as clinically effective drugs, while G-quadruplex (G4)-targeting compounds are emerging as a promising new strategy to target tumor cells and could support personalized treatment approaches in the near future. G-quadruplex (G4) is a secondary four-stranded DNA helical structure constituted of guanine-rich nucleic acids, and its stabilization impairs telomere replication, triggering the activation of several protein factors at telomere levels, including Topos. Thus, the pharmacological intervention through the simultaneous G4 stabilization and Topos inhibition offers a new opportunity to achieve greater antiproliferative activity and circumvent cellular insensitivity and resistance. In this line, dual ligands targeting both Topos and G4 emerge as innovative, efficient agents in cancer therapy. Although the research in this field is still limited, to date, some chemotypes have been identified, showing this dual activity and an interesting pharmacological profile. This paper reviews the available literature on dual Topo inhibitors/G4 stabilizing agents, with particular attention to the structure–activity relationship studies correlating the dual activity with the cytotoxic activity.

Engineering Ultrasmall Metal Nanoclusters as Promising Theranostic Agents

Inflammation is closely linked to cancer, and many anti-cancer agents are also used to treat inflammatory diseases, such as rheumatoid arthritis. Moreover, chronic inflammation increases the risk for various cancers, indicating that eliminating inflammation may represent a valid strategy for cancer prevention and therapy. This article explores the relationship between inflammation and cancer with an emphasis on epidemiological evidence, summarizes the current use of anti-inflammatory agents for cancer prevention and therapy, and describes the mechanisms underlying the anti-cancer effects of anti-inflammatory agents. Since monotherapy is generally insufficient for treating cancer, the combined use of anti-inflammatory agents and conventional cancer therapy is also a focal point in discussion. In addition, we also briefly describe future directions that should be explored for anti-cancer anti-inflammatory agents.

Proteomics and bioinformatics analysis of lovastatin-induced differentiation in ARO cells

Bio-nanoconjugates of lithocholic acid/IR 780 for ROS-mediated apoptosis and optoacoustic imaging applications in breast cancer

The role of inhibitors of poly(ADP-ribose) polymerase as resistance-modifying agents in cancer therapy

Mechanisms of Action of Immunopotentiating Agents in Cancer Therapy

The photo-efficacy of oncological phototherapy for both internal and external tumors is encouraging. When light and photochemotherapeutic drugs are applied together, precise cancer targeting, minimal invasiveness, and innovative modes of action are made possible. Current developments in photoactive compounds and new light sources are promising for further advancement. When designing photosensitizers, metal complexes may be advantageous since the metal can enhance stability and photocytotoxicity while facilitating their localization and quantification. The absorption spectra of photosensitizers limit their excitation wavelengths, which impact light tissue penetration that differs in various organs. Since longer wavelength light penetrates deeper, PDT is typically carried out at wavelengths greater than 620 nm. Additionally, employing lower intensity (>4-8 J/cm2) energy can greatly lessen the pain and discomfort induced by red-light PDT. Low-level laser therapy exposure was used to assess the dithiophosphinic acid complexes' photodynamic treatment efficacy in MCF-7 cells. Following the administration of the complexes at concentrations within IC50 values, red light (4 J, 780 nm) was applied to the cells. Afterward, MCF-7 cells were cultured for 24 hours to evaluate the photodynamic effects of the compounds on cancer cells. Cell viability was assessed using the XTT assay kit. DTPA complexes have shown effectiveness as photodynamic agents in cancer therapy, with Ni(II) and Ni(II)-pyridine complexes demonstrating significant cytotoxicity against cancer cells. Light-activated cancer cell therapies are promising, and the synthesized complexes affect the cell cycle and apoptosis-regulating proteins. The compounds can be employed as anticancer agents and a fine starting template for photodynamic drug design.

There is substantial preclinical and clinical evidence that angiogenesis plays a role in the development of tumors and the progression of malignancies. Inhibiting angiogenesis has been shown to suppress tumor growth and metastasis in many preclinical models. These benefits have translated to the clinic with both marketed and investigational antiangiogenesis agents. The most prominent target of these compounds is vascular endothelial growth factor (VEGF) and its receptors. However, several other factors are of interest as well. These include integrins, matrix metalloproteinases, and endogenous antiangiogenic factors. Data from late-stage clinical trials support the role of antiangiogenic agents in cancer therapy and the significant role that VEGF plays in angiogenesis. Future research will focus on determining the tumor types and stages that will benefit most from antiangiogenic therapy and combining therapies that target different factors in the angiogenesis pathway.

Multifunctional nanoparticle–EpCAM aptamer bioconjugates: A paradigm for targeted drug delivery and imaging in cancer therapy

Journal of Labelled Compounds and RadiopharmaceuticalsVolume 44, Issue S1 p. S657-S659 Article Non-carrier-added 186, 188Re labeled 17α-ethynylestradiol: A potential breast cancer imaging and therapy agent M. Faßbender, M. Faßbender Los Alamos National Laboratory, C-INC, Los Alamos, NM 87545, U.S.A.Search for more papers by this authorD. R. Phillips, D. R. Phillips Los Alamos National Laboratory, C-INC, Los Alamos, NM 87545, U.S.A.Search for more papers by this authorK. C. Ott, K. C. Ott Los Alamos National Laboratory, C-SIC, Los Alamos, NM 87545, U.S.A.Search for more papers by this authorJ. B. Arterburn, J. B. Arterburn Department of Chemistry and Biochemistry MSC 3C, New Mexico State University, P.O. Box 30001, Las Cruces, NM 88003, U.S.A.Search for more papers by this author M. Faßbender, M. Faßbender Los Alamos National Laboratory, C-INC, Los Alamos, NM 87545, U.S.A.Search for more papers by this authorD. R. Phillips, D. R. Phillips Los Alamos National Laboratory, C-INC, Los Alamos, NM 87545, U.S.A.Search for more papers by this authorK. C. Ott, K. C. Ott Los Alamos National Laboratory, C-SIC, Los Alamos, NM 87545, U.S.A.Search for more papers by this authorJ. B. Arterburn, J. B. Arterburn Department of Chemistry and Biochemistry MSC 3C, New Mexico State University, P.O. Box 30001, Las Cruces, NM 88003, U.S.A.Search for more papers by this author First published: 23 April 2012 https://doi.org/10.1002/jlcr.25804401232Citations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume44, IssueS1Supplement: Journal of Labelled Compounds and RadiopharmaceuticalsMay 2001Pages S657-S659 RelatedInformation

Cancer remains an important cause of mortality nowadays and, therefore, new therapeutic approaches are still needed. Rosemary (Rosmarinus officinalis L.) has been reported to possess antitumor activities both in vitro and in animal studies. Some of these activities were attributed to its major components, such as carnosic acid, carnosol, ursolic acid, and rosmarinic acid. Initially, the antitumor effects of rosemary were attributed to its antioxidant activity. However, in recent years, a lack of correlation between antioxidant and antitumor effects exerted by rosemary was reported, and different molecular mechanisms were related to its tumor inhibitory properties. Moreover, supported by the U.S. Food and Drug Administration and the European Food and Safety Authority, specific compositions of rosemary extract were demonstrated to be safe for human health and used as antioxidant additive in foods, suggesting the potential easy application of this agent as a complementary approach in cancer therapy. In this review, we aim to summarize the reported anticancer effects of rosemary, the demonstrated molecular mechanisms related to these effects and the interactions between rosemary and currently used anticancer agents. The possibility of using rosemary extract as a complementary agent in cancer therapy in comparison with its isolated components is discussed.

<p>Breast cancer is one of the most common malignancies among women. Mammography and ultrasound imaging modalities are routinely used as breast cancer screening procedures. The sensitivity of those modalities decreases significantly in patients with dense tissues and advanced stage breast cancer. Photoacoustic (PA) imaging, as a non-invasive modality, may offer increased sensitivity for screening breast tumors. To probe additional, specific structural and molecular information, targeted exogenous contrast agents are often introduced. Gold nanorods (GNRs) are effective contrast agents in PA imaging due to their high optical absorption at the near-infrared band and superior biocompatibility. The high spatial localization of GNRs provides significant increases in signal amplitude within the target tissue and assists nanoparticle-mediated cancer therapy. I proposed using targeted theranostic agents containing GNRs for breast tumour detection using a photoacoustic method and laser-activated therapy. In this work, I have developed polymeric nanoparticles (NPs) for the imaging and treatment of breast cancer over-expressing human epidermal growth factor receptor 2 (HER2). These NPs contain a perfluorohexane liquid and gold nanorods (GNRs) interior stabilized by biodegradable and biocompatible copolymer PLGA-PEG. Water-insoluble therapeutic drug Paclitaxel (PAC) and fluorescent dye are encapsulated into the PLGA shell. The NP surfaces are conjugated to the HER2-binding antibody Herceptin to target HER2-positive cancer cells actively. The NP uptake by tumor is evaluated using multi-spectral PA imaging. The effectiveness of cancer cell treatment by laser-induced particle vaporization and stimulated drug release are investigated in vitro. The therapeutic efficacy on tumours is also performed using a xenograft mouse bilateral tumor model. PA quantitative analysis demonstrates that these NPs actively target HER2 positive cells with high efficiency. The laser-induced vaporization causes more damage to the targeted cells versus PAC-only and negative controls. The relative concentrations of GNRs in the tumour with peak signal at 6 hours are quantified using a linear spectral unmixing technique. The therapeutic efficacy of these nanoparticles is evaluated using tissue immunofluorescence and histology. In this dissertation, PLGA-PEG-GNRs as theranostic agents for anti-HER2 breast cancer therapy are developed. They may provide better diagnostic imaging and therapeutic potential than current methods for treating HER2-positive breast cancer.</p>