| The application of doxorubicin (DOX) and methotrexate (MTX) delivery, like other anticancer drugs, is
limited by insufficient targeting to cancerous tissue cells. The development of smart, biocompatible, and
magnetic nanocarriers capable of carrying the anticancer drugs into the cells and releasing them under
cancerous tissue conditions could increase the efficacy of the anticancer drugs currently in use. In this
study, novel dendritic chitosan coated silica magnetic nanoparticles (DCSM NPs) were developed with
the aim of achieving simultaneous intracellular delivery of DOX and MTX, two different common
anticancer drugs. The 3.5th generation of DCSM NPs prepared in this study contain a lot of surface
amino and carboxylic acid groups which allow them to be useful as magnetic nanocarriers for a drug
delivery system (DDS). The synthesized nanoparticles (NPs) were characterized and validated step by
step using FTIR, SEM, EDX, VSM, XRD, DLS and zeta potential analysis methods. DOX and MTX, as model
anticancer drugs, were loaded effectively onto the magnetic nanocarrier through electrostatic
interactions with high loading efficiencies (99.07% and 98.92%, respectively) due to the presence of a high
content of amine and carboxylic acid groups. Drug release studies confirmed that DOX@MTX@nanocarrier
is a suitable candidate for cancer treatment because it maintains a low drug release in the simulated blood
stream under physiological conditions (pH 7.4) while having a high drug release rate under cancerous
conditions (pH 5.4 and 4.0). We hypothesize that the co-delivery of DOX with MTX could act synergistically
to increase their treatment efficacy and reduce their toxic side effects. The cytotoxicity assay of a blank
nanocarrier to MCF7 cell lines indicated that the 3.5th generation of DCSM NPs were suitable as
anticancer drugs nanocarriers. On the other hand, the DOX@MTX@nanocarrier had an efficient
anticancer performance, as confirmed by MTT assay, DAPI staining, cellular uptake, cell cycle, and
real-time PCR analysis compared to free dual anticancer drugs (DOX–MTX). The hemolysis assay results showed
that the nanocarrier has negligible hemolytic effects on human red blood cells (HRBCs) and also has good
biocompatibility. The results of our study showed that the 3.5th generation of DCSM NPs could be effectively
used in the targeted delivery of DOX and MTX to cancerous tissues and for further in vivo uses. |