Combined inhibition of CD73 and ZEB1 by Arg-Gly-Asp (RGD)-targeted nanoparticles inhibits tumor growth.

Abnormal expression of several macromolecules within tumor milieu helps the development of neoplasia and immune suppression in various cancers. ZEB-1 and CD73 are important factors in tumor progression, which their overexpression in tumor site enhances several cancer hallmarks, including proliferation, angiogenesis, metastasis, migration, and invasion. In this study, we decided to inhibit the expression of these factors in the tumor site by using RGD-conjugated chitosan lactate (RGD-CL) nanoparticles (NPs) encapsulating CD73/ZEB-1 siRNA molecules, in vitro and in vivo. The NPs were about 127 nm in size, non-toxic, and RGD conjugation to NPs could efficiently increase cell transfection through interaction with αvß3 integrins expressed on cancer cells and tumoral endothelial cells.Moreover, RGD-conjugated CL NPs containing siRNAs could significantly reduce the ZEB-1 and CD73 expression levels in cancer cells. Following transfection, cancer cells showed a significant reduction in migration and proliferation. Furthermore, the administration of these NPs into 4T1 and CT26 tumor-bearing mice resulted in tumor suppression and prolonged survival. These findings indicate the importance of targeting the CD73/ZEB1 axis in cancer cells, which could encourage their use in cancer patients in the near future.

Codelivery of BV6 and anti-IL6 siRNA by hyaluronate-conjugated PEG-chitosan-lactate nanoparticles inhibits tumor progression.

AIMS: Increased expression of inhibitor of apoptosis (IAP) genes has been associated with progressive cancer and chemoresistance. Accordingly, blockade of IAPs by BV6 has resulted in ameliorative outcomes. Interleukin (IL)-6 is another important mediator involved in the growth and survival of tumor cells. Therefore, we hypothesized that simultaneous inhibition of IAPs and IL-6 could be a new promising anti-tumor treatment strategy. MATERIALS AND METHODS: In this study, we generated and characterized hyaluronate-PEG-Chitosan-Lactate (H-PCL) nanoparticles (NPs) to simultaneously deliver IL6-specific siRNA and BV6 to 4T1 (breast cancer) and CT26 (colon cancer) cells, and investigate the anti-tumor properties of this combination therapy both in vitro and in vivo. KEY FINDINGS: H-PCL NPs exhibited good physicochemical properties leading to efficient transfection of cancer cells and suppression of target molecules. Moreover, combination therapy synergistically increased apoptosis, as well as decreased cell migration, proliferation, colony formation, and angiogenesis in both 4T1 and CT26 cell lines and suppressed cancer progression in tumor-bearing mice that was associated with enhanced survival time. SIGNIFICANCE: These findings imply the effectiveness of cancer combination therapy by using H-PCL NPs loaded with anti-IL-6 siRNA and BV6.

Cylindrical agar gel with fluid flow subjected to an alternating magnetic field during hyperthermia.

PURPOSE: In magnetic fluid hyperthermia (MFH), nanoparticles are injected into diseased tissue and subjected to an alternating high frequency magnetic field. The process triggers sufficient heat to destroy the cancerous cells. One of the challenging problems during MFH is blood flow in tissue. In real conditions the heat which is transferred by blood flow should be considered in the analysis of MFH. METHODS: In this study, heat transfer was investigated in an agar gel phantom containing fluid flow. Fe3O4 as a nano-fluid was injected into the centre of a gel cylinder which was filled with another gel cylinder and subjected to an alternating magnetic field of 7.3 kA/m and a frequency of 50 kHz for 3600 s. The temperature was measured at three points in the gel. Temperature distributions regarding the time at these three points were experimentally measured. Moreover, the specific absorption rate (SAR) function was calculated with a temperature function. RESULTS: The SAR function was a key asset in the hyperthermia and was obtained on the condition that the fluid flowed through the gel. Finally, a finite element analysis (FEA) was performed to verify the SAR function. The results revealed that there was good agreement between the measured temperature and the one obtained from FEA. In addition, the effects of fluid flow and accuracy of function obtained for heat production in the gel were presented. CONCLUSION: It is believed that the proposed model has the potential ability to get close to reality in this type of investigation. The proposed function has implications for use in further modelling studies as a heat generation source.