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1.
Biomed Pharmacother ; 147: 112672, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35104698

RESUMEN

Novel functions and involvement of circFARSA have not been reported in pancreatic cancer; in addition, its inhibitor screening has not yet been conducted. The purpose of this study was to (1) verify circFARSA as a novel anti-cancer target for pancreatic cancer and (2) to prepare a novel anti-pancreatic cancer agent targeting circFARSA. In this study, we designed and synthesized a small interfering RNA (siRNA, named siRNA-circFARSA), which specifically inhibits circFARSA expression. Using liposomes and porous silicon nanoparticles (pSiNPs) as siRNA delivery system, we prepared liposome-siRNA-circFARSA and pSiNP-PEI-siRNA-circFARSA and investigated their anti-cancer mechanism by quantitative real-time PCR and western blotting. Cell proliferation curves and transwell migration assays were performed to investigate the effect of siRNAs proliferation and migration capabilities of cancer cells. Patient-derived tumor xenograft mouse models were used to investigate the anti-cancer effects in vivo. The data showed that both liposome-siRNA-circFARSA and pSiNP-PEI-siRNA-circFARSA (Si: 0.7 µg/mL) significantly inhibited the proliferation and migration of pancreatic cancer cells in vitro. However, the biological safety and in vivo anti-cancer effects of pSiNP-PEI-siRNA-circFARSA (Si: 22.4 µg/mL) were higher than those of liposome-siRNA-circFARSA. The results showed that siRNA-circFARSA could inhibit the expression of circFARSA and then BCL-2 protein expression, thereby leading to pancreatic cancer cell apoptosis after transportation into pancreatic cancer cells. Therefore, this study provides tools for pancreatic cancer treatment in the future, as it (1) verified circFARSA as a novel target for pancreatic cancer treatment, and (2) prepared a novel anti-pancreatic cancer agent (pSiNP-PEI-siRNA-circFARSA).


Asunto(s)
Nanopartículas/química , Neoplasias Pancreáticas/patología , ARN Circular/antagonistas & inhibidores , ARN Interferente Pequeño/farmacología , Silicio/química , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Silenciador del Gen , Humanos , Liposomas/química , Masculino , Ratones , Ratones Desnudos , ARN Interferente Pequeño/administración & dosificación , Ensayos Antitumor por Modelo de Xenoinjerto
2.
Nanoscale Res Lett ; 16(1): 124, 2021 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-34331597

RESUMEN

At present, various fluorescent nanomaterials have been designed and synthesized as optical contrast agents for surgical navigation. However, there have been no reports on the preparation of fluorescent contrast agents for lung cancer surgery navigation using silicon quantum dots (Si QDs). This study improved and modified the water-dispersible Si QD micelles reported by Pi et al. to prepare Si QD micelles-CKAP4. The data showed that the Si QD micelles-CKAP4 were spherical particles with a mean hydrodiameter of approximately 78.8 nm. UV-visible absorption of the Si QD micelles-CKAP4 ranged from 200 to 500 nm. With an excitation wavelength of 330 nm, strong fluorescence at 640 nm was observed in the fluorescence emission spectra. Laser confocal microscopy and fluorescence microscopy assay showed that the Si QD micelles-CKAP4 exhibited good targeting ability to lung cancer cells and lung cancer tissues in vitro. The in vivo fluorescence-imaging assay showed that the Si QD micelles-CKAP4 was metabolized by the liver and excreted by the kidney. In addition, Si QD micelles-CKAP4 specifically targeted lung cancer tissue in vivo compared with healthy lung tissue. Cytotoxicity and hematoxylin and eosin staining assays showed that the Si QD micelles-CKAP4 exhibited high biosafety in vitro and in vivo. Si QD micelles-CKAP4 is a specifically targeted imaging agent for lung cancer and is expected to be a fluorescent contrast agent for lung cancer surgical navigation in the future.

3.
Nanomedicine ; 33: 102348, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33321215

RESUMEN

Atherosclerosis can lead to most cardiovascular diseases. Although some biomimetic nanomaterials coated by macrophage membranes have been reported in previous studies of atherosclerosis, to our knowledge, no studies regarding the detection of early lesions of atherosclerosis (foam cells) using such a strategy have yet been reported. In the present study, Fe3O4 biomimetic nanoparticles coated with a macrophage membrane (Fe3O4@M) were prepared to investigate the imaging effect on the early lesions of atherosclerosis (foam cells). The results showed that the Fe3O4@M particles are spheres with average diameters of approximately 300 nm. T1 and T2 relaxation values showed that the ratio of r2 to r1 was 26.09. The protein content accounted for approximately 27% of the total weight in Fe3O4@M, and Fe3O4@M nanoparticles exhibited high biosafety. Further testing showed that Fe3O4@M effectively targets early atherosclerotic lesions by the specific recognition of integrin α4ß1 to VCAM-1. Taken together, Fe3O4@M is a promising contrast agent for the diagnosis of early stage atherosclerosis.


Asunto(s)
Materiales Biomiméticos/química , Medios de Contraste/química , Nanopartículas de Magnetita/química , Animales , Aterosclerosis , Permeabilidad de la Membrana Celular , Supervivencia Celular/efectos de los fármacos , Humanos , Macrófagos/química , Macrófagos/metabolismo , Imagen por Resonancia Magnética , Ratones , Células RAW 264.7 , Propiedades de Superficie , Molécula 1 de Adhesión Celular Vascular/metabolismo
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