Hyperthermia Enhances The Effect Of Magnetic Fe3O4nanoparticle Loaded With Daunorubicin On Leukemia and Drug Accumulation In Tumor In Vivo

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5038-5038 ◽  
Author(s):  
Ran Liu ◽  
Weiwei Wu ◽  
Baoan Chen ◽  
Jian Cheng ◽  
Jun Wang ◽  
...  

Abstract Multidrug resistance in cancer and adverse effects of chemotherapy are the major obstacles for cancer therapeutics. This study was aimed to investigate the efficiency of novel multifunctional Fe3O4 magnetic nanoparticles combined with chemotherapeutic agents and hyperthermia in order to reverse multidrug resistance and reduce side effects by concentrating chemotherapeutics on the target site in vivo leukemia models. K562 and K562/A02 xenograft tumor-bearing nude mice were randomly divided into 4 groups, a control group and the treatment groups were allocated to receive daunorubicin (DNR), Fe3O4 magnetic nanoparticles (Fe3O4-MNP), and Fe3O4 magnetic nanoparticles loaded with daunorubicin (DNR-Fe3O4-MNP). All groups were subjected to hyperthermia in an alternating magnetic field. Tumor volume was measured with a vernier caliper. Daunorubicin concentrations in plasma, tumor and non-tumor tissues were determined by high performance liquid chromatography (HPLC). Tumor and non-tumor tissues were stained with Hematoxylin and Eosin for histopathological and microscopic examination. Locations of Fe3O4 magnetic nanoparticles in tumor tissues were stained with Prussian blue for microscope examination. In Fe3O4-MNP and DNR-Fe3O4-MNP treated groups of both K562 and K562/A02 xenograft models, tumor temperature obviously increased and tumor volume became significantly smaller.  Apoptosis was observed in tumor cells treated with  DNR-Fe3O4-MNP groups.  In all DNR-Fe3O4-MNP groups of K562 and K562/A02 xenograft tumor models, the tumor inhibition rate, daunorubicin concentration  were higher level and  daunorubicin clearance in kidney also was delayed when compared with DNR alone treated group. Location of Fe3O4 magnetic nanoparticles with Prussian blue staining showed that Fe3O4 magnetic nanoparticles could be seen in tumor tissues. No obvious histopathological damage was observed in other non-tumor tissues.  Fe3O4 magnetic nanoparticles played an important role in increasing tumor temperature during hyperthermia, and can be delivered successfully to tumor site in an alternating magnetic field. Fe3O4 magnetic nanoparticles loaded with daunorubicin with hyperthermia had the strongest inhibitory effect on tumor and would be potential approach for improving the efficacy of chemotherapeutics, reducing side effects and reversing multidrug resistance in the treatment of leukemia. Disclosures: No relevant conflicts of interest to declare.

2019 ◽  
Vol 10 (11) ◽  
Author(s):  
Mengxuan Zhu ◽  
Weiyue Xu ◽  
Chuanyuan Wei ◽  
Jing Huang ◽  
Jietian Xu ◽  
...  

Abstract CCL14 is a member of CC chemokines and its role in hepatocellular carcinoma (HCC) is still unknown. In this study, CCL14 expression were analyzed by tissue microarray (TMA) including 171 paired tumor and peritumor tissues of patients from Zhongshan Hospital of Fudan University. We found for the first time that CCL14 was downregulated in HCC tumor tissues compared with peritumor tissues (P = 0.01). Meanwhile, CCL14 low expression in HCC tumor tissues is associated with a poor prognosis (P = 0.035). CCL14 also displayed its predictive value in high differentiation (P = 0.026), liver cirrhosis (P = 0.003), and no tumor capsule (P = 0.024) subgroups. The underlying mechanisms were further investigated in HCC cell lines by CCL14 overexpression and knock-down in vitro. We found overexpression of CCL14 suppressed proliferation and promoted apoptosis of HCC cells. Finally, the effect was confirmed by animal xenograft tumor models in vivo. The results shown overexpression of CCL14 lead to inhibiting the growth of tumor in nude mice. Interestingly, our data also implied that CCL14 played these effects by inhibiting the activation of Wnt/β-catenin pathway. These findings suggest CCL14 is a novel prognostic factor of HCC and serve as a tumor suppressor.


2021 ◽  
Vol 11 ◽  
Author(s):  
Junxiao Wang ◽  
Rui Liu ◽  
Yun Zhao ◽  
Zhenhu Ma ◽  
Zejie Sang ◽  
...  

The tyrosine kinase inhibitors (TKIs), including sorafenib, remain one first-line antitumor treatment strategy for advanced hepatocellular carcinoma (HCC). However, many problems exist with the current orally administered TKIs, creating a heavy medical burden and causing severe side effects. In this work, we prepared a novel microcrystalline formulation of sorafenib that not only achieved sustainable release and long action in HCC tumors but also relieved side effects, as demonstrated by fundus microcirculation imaging. The larger the size of the microcrystalline formulation of sorafenib particle, the slower the release rates of sorafenib from the tumor tissues. The microcrystalline formulation of sorafenib with the largest particle size was named as Sor-MS. One intratumor injection (once administration) of Sor-MS, but not Sor-Sol (the solution formulation of sorafenib as a control), could slow the release of sorafenib in HCC tumor tissues and in turn inhibited the in vivo proliferation of HCC or the expression of EMT/pro-survival–related factors in a long-acting manner. Moreover, compared with oral administration, one intratumor injection of Sor-MS not only facilitated a long-acting antitumor effect but also relieved side effects of sorafenib, avoiding damage to the capillary network of the eye fundus, as evidenced by fundus microcirculation imaging. Therefore, preparing sorafenib as a novel microcrystal formulation could facilitate a long-acting antitumor effect and relieve drug-related side effects.


2013 ◽  
Vol 5 (13) ◽  
pp. 5976-5985 ◽  
Author(s):  
Jialong Chen ◽  
Nan Huang ◽  
Baolong Ma ◽  
Manfred F. Maitz ◽  
Juan Wang ◽  
...  

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1927
Author(s):  
Artem A. Sizikov ◽  
Petr I. Nikitin ◽  
Maxim P. Nikitin

Nanoparticle-based technologies are rapidly expanding into many areas of biomedicine and molecular science. The unique ability of magnetic nanoparticles to respond to the magnetic field makes them especially attractive for a number of in vivo applications including magnetofection. The magnetofection principle consists of the accumulation and retention of magnetic nanoparticles carrying nucleic acids in the area of magnetic field application. The method is highly promising as a clinically efficient tool for gene delivery in vivo. However, the data on in vivo magnetofection are often only descriptive or poorly studied, insufficiently systematized, and sometimes even contradictory. Therefore, the aim of the review was to systematize and analyze the data that influence the in vivo magnetofection processes after the systemic injection of magnetic nanostructures. The main emphasis is placed on the structure and coating of the nanomagnetic vectors. The present problems and future trends of the method development are also considered.


2021 ◽  
Vol 11 (8) ◽  
pp. 1347-1353
Author(s):  
Yuhui Luo ◽  
Mingyan Wang ◽  
Li Zhang ◽  
Weining Jia ◽  
Erzhe Wengu ◽  
...  

The work verified that baicalein (BCN) inhibited the appearance and progress of cervical cancer in vitro and in vivo. MTT and CCK-8 methods were used to detect the toxicity of BCN to C33A cells and the number of C33A cells, respectively. For in vivo assays, a solid tumor model of cervical cancer and ascites tumor model was successfully established. The body weight, tumor volume and weight, survival time, and ascites volume were recorded. The anti-tumor ratio and increasing rate of life span were computed. H&E staining was performed to examine the liver tissues, kidney tissues, and tumor tissues. BCN inhibits the proliferation of human cervical cancer cell line C33A and induces apoptosis. The results from in vivo assays showed that BCN suppressed tumor growth and progression with decreased tumor volume and weight in a solid tumor model. BCN significantly induced cell apoptosis in solid tumor tissues. BCN also reduced ascites volume, prolonged survival time, and increased life extension rate in the ascites tumor model. These findings indicated that BCN exerted an antitumor effect against cervical cancer both in vitro and in vivo. According to the results, BCN might act as an important antitumor agent against cervical cancer.


2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Liu-Lin Xiong ◽  
Ruo-Lan Du ◽  
Jun-Jie Chen ◽  
Ya Jiang ◽  
Lu-Lu Xue ◽  
...  

Background. Colorectal cancer (CRC) is an underlying deadly malignancy with poor prognosis, lacking effective therapies currently available to improve the prognosis. C18H17NO6 (AUCAN), a kind of dibenzofuran extracted from a special plant in Yunnan Province (China), is identified as a natural anticancer agent exerting strong inhibitory activities on various cancers. Our study was committed to investigating the potency of AUCAN against colorectal cancers and further exploring the potential mechanisms via proteomic analysis. Methods. Cell Counting Kit-8 assay and immunofluorescence staining were used to investigate the effect of AUCAN on the viability and proliferation of HCT-116 cells and RKO cells. The apoptosis of HCT-116 and RKO cells after AUCAN administration was determined by the flow cytometry test. The effects of AUCAN on invasion and migration of tumor cells were investigated by the colony formation assay, wound healing test, and Transwell invasion test. Meanwhile, the energy metabolism and growth of tumor tissues after AUCAN administration with 10 mg/kg and 20 mg/kg were examined by PET-CT in vivo. The side effects of AUCAN treatment were also evaluated through blood routine and liver function examination. RKO cell proliferation and apoptosis in vivo were further determined by hematoxylin and eosin staining, TUNEL staining, and immunohistochemistry. Furthermore, the differentially expressed proteins (DEPs) involved in AUCAN treatment were determined by proteomic analysis followed by functional clustering analysis. Results. The results showed that AUCAN suppressed the migratory abilities and enhanced apoptosis of HCT-116 and RKO cell lines. Meanwhile, AUCAN treatment dramatically depressed the growth and volume of colorectal tumors in nude mice and suppressed the survival of RKO cells in tumor tissues without any side effects on the blood routine and liver function. In addition, twenty-four upregulated and forty-two downregulated proteins were identified. Additionally, functional clustering analysis concealed enriched biological processes, cellular components, molecular functions, and related pathways of these proteins involved in cellular metabolic. Finally, the protein-protein interaction analysis revealed the regulatory connection among these DEPs. Conclusions. Taken together, AUCAN exerted its significant antitumor effect without side effects in the blood routine and liver function and the underlying mechanisms were preliminarily investigated by proteomic analysis.


Author(s):  
S. Shaw ◽  
P. Sibanda ◽  
P. V. S. N. Murthy

A mathematical model is presented for predicting magnetic targeting of multifunctional carrier particles that deliver therapeutic agents to malignant tissue in vivo. These particles consist of a nonmagnetic core material that contains embedded magnetic nanoparticles and therapeutic agents such as photodynamic sensitizers. For in vivo therapy, the particles are injected into the micro vascular system upstream from malignant tissue, and captured at the tumor using an applied magnetic field. In this paper, a mathematical model is developed for predicting noninvasive magnetic targeting of therapeutic carrier particles in a micro vessel. The flow of blood in the micro vessel is described by a two phase Herschel-Bulkley fluid model. The Brinkmann model is used to characterize the permeable nature of the inner wall of the micro-vessel. The fluidic force on the carrier traversing the micro-vessel and the magnetic force due to the external magnetic field is taken into account. The model enables rapid parametric analysis of magnetic targeting as a function of key variables including the size of the carrier particle, the properties and volume fraction of the imbedded magnetic nanoparticles, the properties of the magnet, the micro vessel and the permeability of the micro vessel.


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