scholarly journals Laser-triggered combination therapy by iron sulfide-doxorubicin@functionalized nanozymes for breast cancer therapy

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Shipeng Ning ◽  
Yang Zheng ◽  
Kun Qiao ◽  
Guozheng Li ◽  
Qian Bai ◽  
...  

Abstract Background The use of magnetic nanozymes (NZs) with the ability to synchronize gas therapy through photodynamic and chemotherapy in the treatment of breast cancer has received much attention. Results Hence, in this study, we designed a bovine lactoferrin-coated iron sulfide NZs containing doxorubicin (abbreviated as: FeS-Dox@bLf NZs) by wet-chemical synthesis method. Then, the physicochemical characteristics of synthesized NZs were explored by several methods. Also, the level of Fe2+, H2S and Dox releases from FeS-Dox@Lf NZs. Also, the cytotoxic effects of FeS-Dox@Lf NZs were investigated by cellular assays. After intravenous injections of NZs and laser irradiation, significant effects of FeS-Dox@Lf NZs on mice weight and tumor status were observed. Afterwards, not only the distribution of Dox in the body was examined by fluorescent, but also the time of Fe clearance and the amount of Dox and Fe retention in vital tissues were determined. The findings confirm that FeS-Dox@Lf NZs, in addition to targeted drug distribution in tumor tissue, resulted in superior therapeutic performance compared to free Dox due to reduced Dox side effects in vital tissues, and increased level of free radicals in 4T1 cells. Conclusion Overall, FeS-Dox@Lf NZs with the ability to synchronize chemotherapy and gas therapy raised hopes for more effective treatment of breast cancer. Graphic abstract

2021 ◽  
Author(s):  
Qian Bai

Abstract BackgroundThe use of magnetic nanozymes with the ability to synchronize gas therapy through photodynamic and chemotherapy in the treatment of breast cancer has received much attention. ResultsHence, in this study, we designed a bovine lactoferrin-coated iron sulfide nanozymes containing doxorubicin (FeS-Dox@bLf NZs) by wet chemical synthesis that can respond to tumor acidity. Then, the physicochemical properties of synthesized NZs were investigated by TEM, SEM, DLS and spectroscopic methods. Likewise, the level of Fe2+ release, H2S and Dox from FeS-Dox@Lf NZs under acidic conditions was evaluated. It was observed that Fe2+ and S2- caused significant OH and H2S release through the Fenton reaction. Also, the toxic effects of FeS-Dox@Lf NZs on 4T1 cancerous cells were investigated by MTT and flow cytometry assays. After intravenous injections of NZs and laser irradiation, significant effects of FeS-Dox@Lf NZs on mice weight and tumor status were observed. Afterwards, not only the distribution of Dox in the body was examined by fluorescent, but also the time of Fe clearance and the amount of Dox and Fe retention in vital tissues were determined. The findings confirm that FeS-Dox@Lf NZs, in addition to targeted drug distribution in tumor tissue, resulted in superior therapeutic performance compared to free Dox due to reduced Dox side effects in vital tissues, and increased level of free radicals in 4T1 cells. ConclusionOverall, FeS-Dox@Lf nanozymes with the ability to synchronize chemotherapy and gas therapy raised hopes for more effective treatment of breast cancer.


2021 ◽  
Author(s):  
Shipeng Ning ◽  
Yang Zheng ◽  
Kun Qiao ◽  
Guozheng Li ◽  
Shouping Xu ◽  
...  

Abstract BackgroundThe use of magnetic nanozymes with the ability to synchronize gas therapy through photodynamic and chemotherapy in the treatment of breast cancer has received much attention. ResultsHence, in this study, we designed a bovine lactoferrin-coated iron sulfide nanozymes containing doxorubicin (FeS-Dox@bLf NZs) by wet chemical synthesis that can respond to tumor acidity. Then, the physicochemical properties of synthesized NZs were investigated by TEM, SEM, DLS and spectroscopic methods. Likewise, the level of Fe2+ release, H2S and Dox from FeS-Dox@Lf NZs under acidic conditions was evaluated. It was observed that Fe2+ and S2- caused significant OH and H2S release through the Fenton reaction. Also, the toxic effects of FeS-Dox@Lf NZs on 4T1 cancerous cells were investigated by MTT and flow cytometry assays. After intravenous injections of NZs and laser irradiation, significant effects of FeS-Dox@Lf NZs on mice weight and tumor status were observed. Afterwards, not only the distribution of Dox in the body was examined by fluorescent, but also the time of Fe clearance and the amount of Dox and Fe retention in vital tissues were determined. The findings confirm that FeS-Dox@Lf NZs, in addition to targeted drug distribution in tumor tissue, resulted in superior therapeutic performance compared to free Dox due to reduced Dox side effects in vital tissues, and increased level of free radicals in 4T1 cells. ConclusionOverall, FeS-Dox@Lf nanozymes with the ability to synchronize chemotherapy and gas therapy raised hopes for more effective treatment of breast cancer.


Author(s):  
Shamim Mushtaq

Uninhibited proliferation and abnormal cell cycle regulation are the hallmarks of cancer. The main role of cyclin dependent kinases is to regulate the cell cycle and cell proliferation. These protein kinases are frequently down regulated or up regulated in various cancers. Two CDK family members, CDK 11 and 12, have contradicting views about their roles in different cancers. For example, one study suggests that the CDK 11 isoforms, p58, inhibits growth of breast cancer whereas, the CDK 11 isoform, p110, is highly expressed in breast tumor. Studies regarding CDK 12 show variation of opinion towards different parts of the body, however there is a consensus that upregulation of cdk12 increases the risk of breast cancer. Hence, CDK 11 and CDK 12 need to be analyzed to confirm their mechanism and their role regarding therapeutics, prognostic value, and ethnicity in cancer. This article gives an outline on both CDKs of information known up to date from Medline, PubMed, Google Scholar and Web of Science search engines, which were explored and thirty relevant researches were finalized.


2020 ◽  
Vol 21 ◽  
Author(s):  
Sonali Mehendale-Munj

: Breast Cancer Resistance Protein (BCRP) is an efflux transporter responsible for causing multidrug re-sistance(MDR). It is known to expel many potent antineoplastic drugs, owing to its efflux function. Efflux of chemothera-peutics because of BCRP develops resistance to manydrugs, leading to failure in cancer treatment. BCRP plays an important role in physiology by protecting the organism from xenobiotics and other toxins. It is a half-transporter affiliated to theATP-binding cassette (ABC) superfamily of transporters, encoded by the gene ABCG2 and functions in response to adenosine triphosphate (ATP). Regulation of BCRP expression is critically controlled at molecular levels which help in maintaining the balance of xenobiotics and nutrients inside the body. Expression of BCRP can be found in brain, liver, lung cancers and acute myeloid leukemia (AML). Moreover, it is also expressed at high levels in stem cells and many cell lines. This frequent expression of BCRP has an impact on the treatment procedures and if not scrutinized may lead to failure of many cancer therapies.


2019 ◽  
Vol 16 (3) ◽  
pp. 251-258 ◽  
Author(s):  
Javad Behravan ◽  
Atefeh Razazan ◽  
Ghazal Behravan

Breast cancer is the second leading cause of cancer death among women. National cancer institute of the US estimates that one in eight women will be diagnosed with breast cancer during their lifetime. Considering the devastating effects of the disease and the alarming numbers many scientists and research groups have devoted their research to fight breast cancer. Several recommendations are to be considered as preventing measures which include living a healthy lifestyle, regular physical activity, weight control and smoking cessation. Early detection of the disease by annual and regular mammography after the age of 40 is recommended by many healthcare institutions. This would help the diagnosis of the disease at an earlier stage and the start of the treatment before it is spread to other parts of the body. Current therapy for breast cancer includes surgical ablation, radiotherapy and chemotherapy which is often associated with adverse effects and even may lead to a relapse of the disease at a later stage. In order to achieve a long-lasting anticancer response with minimal adverse effects, development of breast cancer vaccines is under investigation by many laboratories. The immune system can be stimulated by a vaccine against breast cancer. This approach has attracted a great enthusiasm in recent years. No breast cancer vaccines have been approved for clinical use today. One breast cancer vaccine (NeuVax) has now completed clinical trial phase III and a few preventive and therapeutic breast cancer vaccines are at different steps of development. We think that with the recent advancements in immunotherapy, a breast cancer vaccine is not far from reach.


Author(s):  
Mingliang Fan ◽  
Jiping Li

Background: The combination of two or more therapeutic drugs is an attractive approach to improve the treatment of experimental tumors. Leveraging nanocarriers for combinational drug delivery can allow a control over drug biological fate and promote co-localization in the same area of the body. However, there are certain concerns regarding the biodegradability and potential long-term toxicity arising from these synthetic nanoscale carriers. Objective: Our aim was to develop a combinational nanodrug delivery system formed by self-assembling of amphiphilic drug molecules,minimizing potential toxicities associated with using additional synthetic nanocarriers. Methods: A novel prodrug chlorambucil gemcitabine conjugate was synthesized, this prodrug was used for the encapsulation of an additional hydrophobic anticancer drug paclitaxel, taking the form of combinational nanodrugs. Particle size and zeta potential were evaluated, cytotoxicity assay and apoptosis/cell cycle analysis were also performed to validate the anticancer efficacy of the combinational nanodrugs. Results: The combinational nanodrugs were acquired by means of nanoprecipitation. In A549 lung adenocarcinoma cell line, cellular assays revealed that co-delivery of low dosage paclitaxel with chlorambucil gemcitabine conjugate can act synergistically to inhibit cell growth and induce accumulation of cells in the G2/M phase with a concomitant decrease in G0/G1 compartment. Conclusion: Chlorambucil gemcitabine conjugate and paclitaxel can co-assemble into composite nanoparticles by a nanoprecipitation process and the resulting combinational nanodrugs showed synergistic anticancer effect. This synthetic nanocarrier-free approach might broaden the nanodrug concept and have potential in cancer therapy.


2020 ◽  
Vol 16 (7) ◽  
pp. 958-968
Author(s):  
Yunrui Cai ◽  
Tong Chen ◽  
Huajian Zhu ◽  
Hongbin Zou

Background: The development of novel antineoplastic agents remains highly desirable. Objective: This study focuses on the design, synthesis, and antitumor evaluation of phenyl ureas bearing 5-fluoroindolin-2-one moiety. Methods: Three sets of phenylureas were designed and synthesized and their antiproliferative ability was measured against four human carcinoma cell lines (Hela, Eca-109, A549, and MCF-7) via MTT assay. In vivo anticancer activity was further evaluated in xenograft models of human breast cancer (MCF-7). Results: A total of twenty-one new compounds were synthesized and characterized by means of 1H and 13C NMR as well as HR-MS. Three sets of compounds (1a‒1c, 2a‒2c, and 3a‒3c) were initially constructed, and preliminary antiproliferative activities of these molecules were evaluated against Hela, Eca-109, A549 and MCF-7, highlighting the meta-substituted phenylureas (1a‒1c) as the most cytotoxic set. A series of meta-substituted phenylureas derivatives (1d‒1o) were then designed and synthesized for structure-activity relationship study. Most of the new compounds showed desirable cytotoxicity, among which compound 1g exhibited the most remarkable cytotoxic effects against the tested human cancer cells with IC50 values ranging from 1.47 to 6.79 μM. Further studies showed that compound 1g suppressed tumor growth in human breast cancer (MCF- 7) xenograft models without affecting the body weight of its recipients. Conclusion: In this study, twenty-one new compounds, containing the privileged structures of phenylurea and 5-fluoroindolin-2-one, were designed and synthesized. Subsequent structureactivity studies showed that 1g was the most bioactive antitumor agent among all tested compounds, hence a potentially promising lead compound once given further optimization.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jennifer K. Lang ◽  
Badri Karthikeyan ◽  
Adolfo Quiñones-Lombraña ◽  
Rachael Hageman Blair ◽  
Amy P. Early ◽  
...  

Abstract Background The CBR3 V244M single nucleotide polymorphism has been linked to the risk of anthracycline-related cardiomyopathy in survivors of childhood cancer. There have been limited prospective studies examining the impact of CBR3 V244M on the risk for anthracycline-related cardiotoxicity in adult cohorts. Objectives This study evaluated the presence of associations between CBR3 V244M genotype status and changes in echocardiographic parameters in breast cancer patients undergoing doxorubicin treatment. Methods We recruited 155 patients with breast cancer receiving treatment with doxorubicin (DOX) at Roswell Park Comprehensive Care Center (Buffalo, NY) to a prospective single arm observational pharmacogenetic study. Patients were genotyped for the CBR3 V244M variant. 92 patients received an echocardiogram at baseline (t0 month) and at 6 months (t6 months) of follow up after DOX treatment. Apical two-chamber and four-chamber echocardiographic images were used to calculate volumes and left ventricular ejection fraction (LVEF) using Simpson’s biplane rule by investigators blinded to all patient data. Volumetric indices were evaluated by normalizing the cardiac volumes to the body surface area (BSA). Results Breast cancer patients with CBR3 GG and AG genotypes both experienced a statistically significant reduction in LVEF at 6 months following initiation of DOX treatment for breast cancer compared with their pre-DOX baseline study. Patients homozygous for the CBR3 V244M G allele (CBR3 V244) exhibited a further statistically significant decrease in LVEF at 6 months following DOX therapy in comparison with patients with heterozygous AG genotype. We found no differences in age, pre-existing cardiac diseases associated with myocardial injury, cumulative DOX dose, or concurrent use of cardioprotective medication between CBR3 genotype groups. Conclusions CBR3 V244M genotype status is associated with changes in echocardiographic parameters suggestive of early anthracycline-related cardiomyopathy in subjects undergoing chemotherapy for breast cancer.


2020 ◽  
Vol 4 (11) ◽  
Author(s):  
Fabian L. M. Bernal ◽  
Bruno Gonano ◽  
Fredrik Lundvall ◽  
David S. Wragg ◽  
Helmer Fjellvåg ◽  
...  

2021 ◽  
Vol 10 (15) ◽  
pp. 3430
Author(s):  
Jeongshin An ◽  
Hyungju Kwon ◽  
Woosung Lim ◽  
Byung-In Moon ◽  
Nam Sun Paik

Breast reconstruction during breast-conserving surgery (BCS) can improve the breast shape. This study introduces breast reconstruction in BCS with two types of acellular dermal matrix (ADM). The study included 134 patients who underwent BCS due to breast cancer from February 2018 to May 2021. This study was conducted by one surgeon, and is the result of a three-year study. The patient group who underwent BCS using ADM was mainly targeted at patients with minor to severe defects after the operation. The average age of the patients was 51.8 years, and the body mass index (BMI) was 23.8 kg/m. The specimen weight was 30–120 g. The average surgical time, including reconstruction, was 100.4 min, combined with reconstruction. There were minor complications in six patients. The advantage of using ADM is that it can quickly correct the shape of the breast after conventional BCS surgery. Pellet-type ADM, rather than sheet-type, can create a breast shape similar to that before surgery. Breast reconstruction using ADM can be an easy and convenient method for making a better shape from BCS.


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