Treatment of breast cancer in vivo by dual photodynamic and photothermal approaches with the aid of curcumin photosensitizer and magnetic nanoparticles

AbstractBreast cancer is a neoplastic disease with a high mortality rate among women. Recently, photodynamic therapy (PDT) and photothermal therapy (PTT) attracted considerable attention because of their minimal invasiveness. The PTT approach works based on hyperthermia generation, and PDT approach employs laser irradiation to activate a reagent named photosensitizer. Therefore, in the current paper, a dual-functioned nanocomposite (NC) was designed for the treatment of breast cancer model in Balb/c mice with the combination of photodynamic and photothermal approaches. Transmission electron microscopy, UV–visible spectroscopy, FTIR, and XRD were employed to validate the nanostructure and silica coating and curcumin (CUR) immobilization on the Fe3O4 nanoparticles. The effect of Fe3O4/SiO2-CUR combined with PDT and PTT was assessed in vivo on the breast tumor mice model, and immunohistochemistry (IHC) was employed to evaluate the expression of apoptotic Bax and Caspase3 proteins. The TEM images, UV–visible absorption, and FTIR spectra demonstrated the successful immobilization of curcumin molecules on the surface of Fe3O4/SiO2. Also, MTT assay confirmed the nontoxic nature of Fe3O4/SiO2 nanoparticles in vitro. In the breast tumor mice model, we have assessed six treatment groups, including control, CUR + PDT, Blue + NIR (near-infrared) lasers, NC, NC + PTT, and NC + PDT + PTT. The tumor volume in the NC + PDT + PTT group showed a significant reduction compared to other groups (p < 0.05). More interestingly, the tumor volume of NC + PDT + PTT group showed a 27% decrease compared to its initial amount. It should be noted that no detectable weight loss or adverse effects on the vital organs was observed due to the treatments. Additionally, the IHC data represented that the expression of proapoptotic Bax and Caspase3 proteins were significantly higher in the NC + PDT + PTT group compared to the control group, indicative of apoptosis. To conclude, our data supported the fact that the NC + PDT + PTT strategy might hold a promising substitute for chemotherapy for the treatment of triple-negative breast cancers.

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Antiproliferation Effects of Nanophytosome-Loaded Phenolic Compounds From Fruit of Juniperus Polycarpos Against Breast Cancer in Mice Model: Synthesis, Characterization and Therapeutic Effects

10.21203/rs.3.rs-1073994/v1 ◽

2021 ◽

Author(s):

Soheila Moeini ◽

Ehsan Karimi ◽

Ehsan Oskoueian

Keyword(s):

Breast Cancer ◽

Negative Control Group ◽

Negative Control ◽

Control Group ◽

Therapeutic Effects ◽

Mice Model ◽

Fruit Extract ◽

Phenolic Fraction ◽

Juniperus Polycarpos

Abstract Background: This research was performed to synthesize nanophytosomes-loaded high phenolic fraction (HPF) from Juniperus polycarpos fruit extract and investigate its antiproliferation effects against breast cancer in mice model. Results: The nanophytosomes-loaded HPF from Juniperus polycarpos fruit extract was synthesized. The mice trial was conducted to determine the possible toxic effects of the synthesized nanophytosomes. The anticancer, pro-apoptotic, and antioxidative activities of the nanophytosomes were determined. The nanophytosomes-loaded HPF had a spherical structure with a size of 176 nm and a polydispersity index coefficient of 0.24. The in-vivo study manifested that nanophytosomes-loaded HPF significantly improved weight gain and food intake compared to the negative control group (p<0.05). The nanophytosomes-loaded HPF significantly enhanced the expression of bax (3.4-fold) and caspase-3 (2.7-fold) genes but reduced bcl2 (3.6-fold) gene expression in tumor cells. The average tumor size was significantly decreased in mice treated with nanophytosomes-loaded HPF (p<0.05). The expression of GPX (2.3-fold) and SOD (2.7-fold) antioxidants in the liver of mice supplemented with nanophytosomes-loaded HPF was significantly developed compared to the negative control (p<0.05). The nanophytosomes-loaded HPF did not show toxicity on normal cells. Conclusion: Our results indicated that nanophytosomes-loaded HPF might be a potential anticancer agent for the breast cancer treatment.

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Bioinspired Drug Delivery Carrier for Enhanced Tumor-Targeting in Melanoma Mice Model

Journal of Biomedical Nanotechnology ◽

10.1166/jbn.2019.2786 ◽

2019 ◽

Vol 15 (7) ◽

pp. 1482-1491 ◽

Cited By ~ 2

Author(s):

Xu Wang ◽

Gao-Feng Liang ◽

Xue-Qin Hao ◽

Shu-Ying Feng ◽

Lu Dai ◽

...

Keyword(s):

Drug Delivery ◽

Near Infrared ◽

Imaging System ◽

Morphological Changes ◽

The Body ◽

Control Group ◽

Mice Model ◽

Normal Tissues ◽

Specific Distribution

As a widely used first-line chemotherapy drug for tumor, Doxorubicin (DOX) can induce various side effects on normal tissues because of its non-specific distribution in the body. Emerging evidence has shown that platelets have the capability to recognize and interact with tumor cells. Inspired by this, the platelet-based drug delivery system was constructed by loading of DOX in platelet cytoplasm and modification of transferrin on the surface of platelet (Tf-P-DOX). The encapsulation efficiency of DOX in platelet was the highest at the DOX concentration of 0.05 mM, and reached to 64.9%. Fluorescence microscopy showed that the Tf-P-DOX facilitated cell uptakes and enhanced intracellular drug accumulation in B16F10 cells. Compared with free DOX, Tf-P-DOX exhibited an enhanced effect on cell apoptosis at the same concentration of DOX. In vivo imaging system showed that the near-infrared fluorescence of B16F10 tumor-bearing mice was mainly accumulated in the tumor site, which caused the inhibition of tumor growth in mice. The morphological changes of tumor tissue in Tf-P-DOX group was significant in comparison with those of the control group, including the small nucleus, the insufficiency of cancerous nest, and the infiltration of inflammatory cells, while Tf-P-DOX did not show significant adverse effects on normal tissues. Compared with the control group, the levels of caspase 9 and caspase 3 protein expressions were increased significantly in Tf-P-DOX group. Our studies suggest platelets can be repurposed as promising carriers for efficient targeting and treatment of solid tumors.

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Anti gC1qR/p32/HABP1 Antibody Therapy Decreases Tumor Growth in an Orthotopic Murine Xenotransplant Model of Triple Negative Breast Cancer

Antibodies ◽

10.3390/antib9040051 ◽

2020 ◽

Vol 9 (4) ◽

pp. 51

Author(s):

Ellinor I. Peerschke ◽

Elisa de Stanchina ◽

Qing Chang ◽

Katia Manova-Todorova ◽

Afsar Barlas ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Tumor Volume ◽

Triple Negative ◽

Antibody Therapy ◽

Vehicle Group ◽

Control Group ◽

Tunel Staining ◽

Cell Counts

gC1qR is highly expressed in breast cancer and plays a role in cancer cell proliferation. This study explored therapy with gC1qR monoclonal antibody 60.11, directed against the C1q binding domain of gC1qR, in a murine orthotopic xenotransplant model of triple negative breast cancer. MDA231 breast cancer cells were injected into the mammary fat pad of athymic nu/nu female mice. Mice were segregated into three groups (n = 5, each) and treated with the vehicle (group 1) or gC1qR antibody 60.11 (100 mg/kg) twice weekly, starting at day 3 post-implantation (group 2) or when the tumor volume reached 100 mm3 (group 3). At study termination (d = 35), the average tumor volume in the control group measured 895 ± 143 mm3, compared to 401 ± 48 mm3 and 701 ± 100 mm3 in groups 2 and 3, respectively (p < 0.05). Immunohistochemical staining of excised tumors revealed increased apoptosis (caspase 3 and TUNEL staining) in 60.11-treated mice compared to controls, and decreased angiogenesis (CD31 staining). Slightly decreased white blood cell counts were noted in 60.11-treated mice. Otherwise, no overt toxicities were observed. These data are the first to demonstrate an in vivo anti-tumor effect of 60.11 therapy in a mouse model of triple negative breast cancer.

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Time-Programmed Delivery of Sorafenib and Anti-CD47 Antibody via a Double-Layer-Gel Matrix for Postsurgical Treatment of Breast Cancer

Nano-Micro Letters ◽

10.1007/s40820-021-00647-x ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Liping Huang ◽

Yiyi Zhang ◽

Yanan Li ◽

Fanling Meng ◽

Hongyu Li ◽

...

Keyword(s):

Breast Cancer ◽

Near Infrared ◽

Immune Escape ◽

Regulatory Protein ◽

In Vivo Studies ◽

Breast Cancer Patients ◽

Thermally Responsive ◽

Immunosuppressive Microenvironment

AbstractThe highly immunosuppressive microenvironment after surgery has a crucial impact on the recurrence and metastasis in breast cancer patients. Programmable delivery of immunotherapy-involving combinations through a single drug delivery system is highly promising, yet greatly challenging, to reverse postoperative immunosuppression. Here, an injectable hierarchical gel matrix, composed of dual lipid gel (DLG) layers with different soybean phosphatidylcholine/glycerol dioleate mass ratios, was developed to achieve the time-programmed sequential delivery of combined cancer immunotherapy. The outer layer of the DLG matrix was thermally responsive and loaded with sorafenib-adsorbed graphene oxide (GO) nanoparticles. GO under manually controlled near-infrared irradiation generated mild heat and provoked the release of sorafenib first to reeducate tumor-associated macrophages (TAMs) and promote an immunogenic tumor microenvironment. The inner layer, loaded with anti-CD47 antibody (aCD47), could maintain the gel state for a much longer time, enabling the sustained release of aCD47 afterward to block the CD47-signal regulatory protein α (SIRPα) pathway for a long-term antitumor effect. In vivo studies on 4T1 tumor-bearing mouse model demonstrated that the DLG-based strategy efficiently prevented tumor recurrence and metastasis by locally reversing the immunosuppression and synergistically blocking the CD47-dependent immune escape, thereby boosting the systemic immune responses.

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Roquin1 Suppresses Breast Cancer Growth by Inducing Cell Cycle Arrest via Selectively Destabilizing Cell Cycle–Promoting Gene mRNAs

10.21203/rs.3.rs-53499/v1 ◽

2020 ◽

Author(s):

Wenbao Lu ◽

Meicen Zhou ◽

Bing Wang ◽

Xueting Liu ◽

Bingwei Li

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cell Proliferation ◽

Cell Cycle Arrest ◽

Breast Cancer Cell ◽

Breast Tumor ◽

Cell Cycle Progression ◽

Cycle Progression ◽

Cycle Arrest

Abstract Background: Dysregulation of cell cycle progression is one of the common features of human cancer cells, however, its mechanism remains unclear. This study aims to clarify the role and the underlying mechanisms of Roquin1 in cell cycle arrest induction in breast cancer.Methods: Public cancer databases were analyzed to identify the expression pattern of Roquin1 in human breast cancers and the significant association with patient survival. Quantitative real-time PCR and western blots were performed to detect the expression of Roquin1 in breast cancer samples and cell lines. Cell counting, MTT assay, flow cytometry, and in vivo study were conducted to investigate the effects of Roquin1 on cell proliferation, cell cycle progression and tumor progression. RNA-sequencing was applied to identify the differential genes and pathways regulated by Roquin1. RNA immunoprecipitation assay, luciferase reporter assay, mRNA half-life detection, RNA affinity binding assay, and RIP-ChIP were used to explore the molecular mechanisms of Roquin1.Results: We showed that Roquin1 expression in breast cancer tissues and cell lines was inhibited, and the reduction in Roquin1 expression was associated with poor overall survival and relapse free survival of patients with breast cancer. Roquin1 overexpression inhibited breast cancer cell proliferation and induced G1/S cell cycle arrest without causing significant apoptosis. In contrast, knockdown of Roquin1 promoted breast cancer cell growth and cycle progression. Moreover, in vivo induction of Roquin1 by adenovirus significantly suppressed breast tumor growth and metastasis. Mechanistically, Roquin1 selectively destabilizing cell cycle–promoting genes, including Cyclin D1, Cyclin E1, cyclin dependent kinase 6 (CDK6) and minichromosome maintenance 2 (MCM2) through targeting the stem–loop structure in the 3’untranslated region (3’UTR) of mRNAs via its ROQ domain, leading to the downregulation of cell cycle–promoting mRNAs.Conclusions: Our findings demonstrated that Roquin1 was a novel breast tumor suppressor and could induce G1/S cell cycle arrest by selectively downregulating the expression of cell cycle–promoting genes, which might as a potential molecular target for breast cancer treatment.

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Co-Treatment with the Epigenetic Drug, 3-Deazaneplanocin A (DZNep) and Cisplatin after DZNep Priming Enhances the Response to Platinum-Based Therapy in Chondrosarcomas

Cancers ◽

10.3390/cancers13184648 ◽

2021 ◽

Vol 13 (18) ◽

pp. 4648

Author(s):

Eva Lhuissier ◽

Juliette Aury-Landas ◽

Marion Lenté ◽

Karim Boumediene ◽

Catherine Baugé

Keyword(s):

Tumor Volume ◽

Mice Model ◽

Antitumoral Effect ◽

Viable Cells ◽

Epigenetic Drug ◽

Xenograft Mice Model ◽

Xenograft Mice ◽

Tumoral Cells

Background: We have previously shown that 3-Deazaneplanocin A (DZNep) induces apoptosis in chondrosarcomas. Herein, we tested whether the combination of this epigenetic drug to a standard anticancer therapy may enhance the response to each drug in these bone tumors. Methods: Two chondrosarcoma cell lines (SW1353 and JJ012) were cultured in the presence of DZNep and/or cisplatin. Cell growth was evaluated by counting viable cells, and apoptosis was determined by Apo2.7 expression by flow cytometry. In vivo, the antitumoral effect of the DZNep/cisplatin combination was assessed through measurements of tumor volume of JJ012 xenografts in nude mice. Results: In vitro, the DZNep/cisplatin combination reduced cell survival and increased apoptosis compared to each drug alone in chondrosarcomas, but not in normal cells (chondrocytes). This enhancement of the antitumoral effect of the DZNep/cisplatin combination required a priming incubation with DZNep before the co-treatment with DZNep/cisplatin. Furthermore, in the chondrosarcoma xenograft mice model, the combination of both drugs more strongly reduced tumor growth and induced more apoptosis in tumoral cells than each of the drugs alone. Conclusion: Our results show that DZNep exposure can presensitize chondrosarcoma cells to a standard anticancer drug, emphasizing the promising clinical utilities of epigenetic-chemotherapeutic drug combinations in the future treatment of chondrosarcomas.

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The CHARACTERIZATION OF SYNERGISTIC EFFECT OF CRILIN AND NANOCURCUMIN ON TREATMENT FOR 7, 12 DIMETHYLBENZ [A] ATHRACENE (DMBA)-INDUCED BREAST CANCER MICE

VNU Journal of Science Medical and Pharmaceutical Sciences ◽

10.25073/2588-1132/vnumps.4099 ◽

2018 ◽

Vol 34 (1) ◽

pp. 61

Author(s):

Gia-Buu Tran

Keyword(s):

Breast Cancer ◽

Synergistic Effect ◽

Tumor Volume ◽

Ductal Carcinoma ◽

Inhibitory Effect ◽

Carcinoma Cells ◽

Herbal Remedies ◽

Surrounding Tissue ◽

Neoplastic Disease

Breast cancer is the neoplastic disease which is characterized by unregulated ductal and lobular hyperplasia. Some herbal remedies have been researched and proved the inhibitory effect on breast cancer such as, Crilin-extracted from Cirnum latifolum and curcumin-isolated from Cucuma longa. However, the synergistic effect of crilin and nanocurcumin have not been studied yet. In this study, we established the mouse model of breast cancer induced by DMBA and evaluated the effectiveness of combination of crilin and nanocurcumin on treatment of breast cancer. After 12 weeks, co-administration of crilin and nanocurcumin inversed alteration of body weight, the number of erythrocytes and leukocytes induced by DMBA. Furthermore, the synergistic effect of crilin and nanocucumin on reduction of tumor volume was proven. Histological analysis revealed that co-administration of crilin and nanocurcumin inhibited invasion of mammary ductal carcinoma cells into surrounding tissue, recovered lobular cells structure, and diminished leukocyte composition. Thereby, the combination of crilin and nanocurcumin recovers immune system and prevent the development of breast cancer.

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Neural Correlates and Functional Cognitive Maps in Breast Cancer Survivors Receiving Different Chemotherapy Regimens; a QEEG/HEG-based Investigation

10.1101/2021.08.28.21262758 ◽

2021 ◽

Author(s):

Maryam Vasaghi Gharamaleki ◽

Seyedeh Zahra Mousavi ◽

Maryam Owrangi ◽

Mohammad Javad Gholamzadeh ◽

Ali-Mohammad Kamali ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Breast Cancer Survivors ◽

Near Infrared ◽

Chemotherapy Regimen ◽

Current Source ◽

Control Group ◽

Breast Cancer Patients ◽

Cognitive Domains ◽

Clinical Disorder

Background: Post-chemotherapy cognitive impairment commonly known as "chemobrain" or "chemofog" is a well-established clinical disorder affecting various cognitive domains including attention, visuospatial working memory, executive function, etc. Although several studies have confirmed the chemobrain in recent years, scant experiments have evaluated the potential neurotoxicity of different chemotherapy regimens and agents. In this study, we aimed to evaluate the extent of attention deficits, one of the commonly affected cognitive domains, among breast cancer patients treated with different chemotherapy regimens through neuroimaging techniques. Methods: Breast cancer patients treated with two commonly prescribed chemotherapy regimens, AC-T and TAC, and healthy volunteers were recruited. Near-infrared hemoencephalography (nirHEG) and quantitative electroencephalography (qEEG) assessments were recorded for each participant at rest and during task performance to compare the functional cortical changes associated with each chemotherapy regimen. Results: The qEEG analysis revealed increased power of high alpha/low beta or sensorimotor rhythm (SMR) frequency in left fronto-centro-parietal regions involved in dorsal and ventral attention networks (DAN and VAN) in the AC-T-treated group comparing to the TAC and control group. The AC-T group also had the highest current source density (CSD) values in DAN and VAN-related centers in 10 and 15 Hz associated with the lowest Z-scored FFT coherence in the mentioned regions. Conclusions: The mentioned findings revealed increased cognitive workload and lack of cognitive ease in breast cancer patients treated with the AC-T regimen proposing the presumable neurotoxic sequelae of this chemotherapy regimen in comparison with the TAC regimen.

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Subtle changes in network composition impact the biodistribution and tumor accumulation of nanogels

Chemical Communications ◽

10.1039/c8cc05627g ◽

2018 ◽

Vol 54 (83) ◽

pp. 11777-11780 ◽

Cited By ~ 7

Author(s):

Ilona Zilkowski ◽

Ioanna Theodorou ◽

Krystyna Albrecht ◽

Frederic Ducongé ◽

Jürgen Groll

Keyword(s):

Breast Tumor ◽

Tumor Targeting ◽

Near Infrared ◽

Side Chain ◽

Human Breast ◽

Human Breast Tumor ◽

Tumor Xenografts ◽

Network Composition ◽

Tumor Accumulation

We studied the effect of subtle changes in side-chain chemistry and labelling with near infrared fluorophores of nanogels (NGs) prepared from thiolated poly(glycidol) on in vivo biodistribution in mice bearing human breast tumor xenografts. Side chain chemistry as well as labelling clearly influenced tumor targeting and overall biodistribution.

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Co-loading of an anthracycline analogue Pirarubicin and Salinomycin in a 1:3 ratio into Quatramerbiodegradable polymeric nanoparticles synergistically inhibit growth of triple-negative breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e15047 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e15047-e15047

Author(s):

Surender Kharbanda ◽

Anees Mohammad ◽

Sachchidanand Tiwari ◽

Neha Mehrotra ◽

Sireesh Appajosyula ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Breast Cancers ◽

Mice Model ◽

Single Drug ◽

Tnbc Cell ◽

Dual Drug

e15047 Background: Triple negative breast cancer (TNBC) accounts for about 10-15% of all breast cancers and differ from other types of invasive breast cancers in that they grow and spread faster. TNBCs have limited treatment options and a worse prognosis. Therapy with anthracyclines considered to be one of the most effective agents in the treatment. Unfortunately, resistance to anthracycline therapy is very common due to drug efflux mediated by overexpression of ABC transporter. Pirarubicin (PIRA), an analogue of doxorubicin (DOX), is approved in Japan, Korea and China and is shown to be less cardiotoxic than DOX. Recent studies suggest that cancer stem cells (CSCs) play an important role in tumorigenesis and biology of TNBC. Targeting CSCs may be a promising, novel strategy for the treatment of this aggressive disease. Recent studies have shown that salinomycin (SAL) preferentially targets the viability of CSCs. Methods: SAL and PIRA were co-encapsulated in polylactic acid (PLA)-based block copolymeric nanoparticles (NPs) to efficiently co-deliver these agents to treat TNBC cells. Results: Generated SAL-PIRA co-encapsulated dual drug-loaded NPs showed an average diameter of 110 ± 7 nm, zeta potential of -12.5 mV and PDI of less than 0.25. Both of these anti-cancer agents showed slow and sustained release profile in non-physiological buffer (PBS, pH 7.4) from these dual drug-encapsulated NPs. Additionally, multiple ratios (PIRA:SAL = 3:1, 1:1, 1:3) were encapsulated to generate diverse dual drug-loaded NPs. The results demonstrate that, in contrast to 1:1 and 3:1, treatment of TNBC cells with 1:3 ratio of PIRA:SAL dual drug-loaded NPs, was associated with significant inhibition of growth in vitro in multiple TNBC cell lines. Interestingly, PIRA:SAL (1:3) was synergistic as compared to either SAL- or PIRA single drug-loaded NPs. The IC50 of PIRA and SAL in single drug-encapsulated NPs is 150 nM and 700 nM respectively in MDA-MB-468. Importantly, the IC50 of PIRA in dual drug-encapsulated NPs dropped down to 30 nM (5-fold). Similar results were obtained in SUM-149 TNBC cell line. Studies are underway to evaluate in vivo biological activity of PIRA:SAL (1:3) on tumor growth in a TNBC xenograft mice model. Conclusions: These results demonstrate that a novel dual drug-loaded NP formulation of PIRA and SAL in a unique ratio of 1:3 represents an approach for successful targeting of CSCs and bulk tumor cells in TNBC and potentially other cancer types.

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