RESUMEN
Floxuridine is a potential clinical anticancer drug for the treatment of various cancers. However, floxuridine typically causes unfavorable side effects due to its very poor tumor selectivity, and, hence, there is a high demand for the development of novel approaches that permit the targeted delivery of floxuridine into cancerous cells. Herein, the design and synthesis of an esterase-responsive multifunctional nanoformulation for the targeted delivery of floxuridine in esterase-overexpressed cancer cells is reported. Photopolymerization of floxuridine-tethered lipoic acid results in the formation of amphiphilic floxuridine-tethered poly(disulfide). Self-assembly of the amphiphilic polymer results in the formation of nanoparticles with floxuridine decorated on the surfaces of the particles. Integration of aptamer DNA for nucleolin onto the surface of the nanoparticle is demonstrated by exploring the base-pairing interaction of floxuridine with adenine. Targeted internalization of the aptamer-decorated nanoparticle into nucleolin-expressed cancer cells is demonstrated. Esterase triggered cleavage of the ester bond connecting floxuridine with the polymer backbone, and the subsequent targeted delivery of floxuridine into cancer cells is also shown. Excellent therapeutic efficacy is observed both in vitro and also in the 3D tumor spheroid model. This noncovalent strategy provides a simple yet effective strategy for the targeted delivery of floxuridine into cancer cells in a less laborious fashion.
Asunto(s)
Antineoplásicos , Esterasas , Floxuridina , Nanopartículas , Humanos , Esterasas/metabolismo , Nanopartículas/química , Antineoplásicos/química , Antineoplásicos/farmacología , Floxuridina/química , Floxuridina/farmacología , Floxuridina/administración & dosificación , Tamaño de la Partícula , Ensayo de Materiales , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/síntesis química , Ensayos de Selección de Medicamentos Antitumorales , Supervivencia Celular/efectos de los fármacos , Estructura Molecular , Proliferación Celular/efectos de los fármacos , Sistemas de Liberación de Medicamentos , Línea Celular TumoralRESUMEN
Scientific evidence on the benefits of yoga among patients undergoing dental implant surgery is sparse. The objective of the present study was to evaluate the effect of performing yoga on the vital signs and salivary cortisol in patients undergoing dental implant surgery. This study was conducted in an outpatient prosthodontics clinic during June-July 2019 as a pilot outcome assessor-blinded randomized trial with parallel design. A total of 20 patients requiring dental implant surgery were divided into two groups, with 10 patients in each group. Control group patients underwent implant surgery without yoga. In the intervention group, patients were trained to perform yoga, which included breathing exercises and meditation practiced for 10 minutes, and then underwent implant surgery. Vital signs (systolic blood pressure, diastolic blood pressure, heart rate, respiratory rate, and temperature) and salivary cortisol were recorded before (baseline) and after (post-surgery) implant surgery in both groups. There was no significant difference in the baseline values between the control and intervention groups. Mean vital sign and salivary cortisol values significantly increased from baseline to post-surgery in the control group. All vital signs except salivary cortisol significantly decreased from baseline to postsurgery in the yoga intervention group. Heart rate and temperature showed significant decreases in postsurgery values between the control and intervention groups. There was no significant correlation between vital signs and salivary cortisol at baseline and postsurgery between the control and intervention groups. This study provides preliminary evidence for the beneficial effects of yoga in reducing anxiety and stress in those undergoing dental implant surgery.