Abstract
Cationic polymeric nanoparticles (NPs) have the ability to overcome biological membranes, leading to improved efficacy of anticancer drugs. The modulation of the particle-cell interaction is desired to control this effect and avoid toxicity to normal cells. In this study, we explored the surface functionalization of cationic polymethylmethacrylate (PMMA) NPs with two natural compounds, sialic acid (SA) and cholesterol (Chol). The performance of benznidazole (BNZ) was assessed in vitro in the normal renal cell line (HEK-293) and three human cancer cell lines, as follows: human colorectal cancer (HT-29), human cervical carcinoma (HeLa), and human hepatocyte carcinoma (HepG2). The structural properties and feasibility of NPs were evaluated and the changes induced by SA and Chol were determined by using multiple analytical approaches. Small (<200 nm) spherical NPs, with a narrow size distribution and high drug-loading efficiency were prepared by using a simple and reproducible emulsification solvent evaporation method. The drug interactions in the different self-assembled NPs were assessed by using Fourier transform-infrared spectroscopy. All formulations exhibited a slow drug-release profile and physical stability for more than 6 weeks. Both SA and Chol changed the kinetic properties of NPs and the anticancer efficacy. The feasibility and potential of SA/Chol-functionalized NPs has been demonstrated in vitro in the HEK-293, HepG2, HeLa, and HT-29 cell lines as a promising system for the delivery of BNZ.
Highlights
Many anticancer drugs induce the generation of intracellular reactive oxygen species (ROS), which cause oxidative stress and cell damage [1]
We explored two natural compounds sialic acid (SA) and Chol, as possible candidates for the functionalization of cationic NPs
All formulations were biocompatible in normal kidney cells (HEK 293) and improved BNZ efficacy, compared to the free drug
Summary
Many anticancer drugs induce the generation of intracellular reactive oxygen species (ROS), which cause oxidative stress and cell damage [1]. We demonstrated the improved biological efficacy of BNZ in human HT-29 colorectal cancer cells through the use of stable, biocompatible, and small-sized cationic nanoparticles (NPs) [5]. The copolymer of N,N-dimethylaminoethyl methacrylate (DMAEMA) with methylmethacrylate (MMA) and butylmethacrylate (BuMA), (PDMAEMA-co-MMA/BMA, 2:1:1 mole ratio) is a well-used cationic polymer for this purpose. It has interesting properties, such as biocompatibility, low toxicity, bioadhesion, and an excellent adsorption capacity [8,9]. In addition to the physical stability, drug protection, and slow drug release, these particles have the ability to escape from the mononuclear phagocyte system (MPS) and overcome biological barriers [10,11]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
