Targeted therapy for human hepatic carcinoma cells using folate-functionalized polymeric micelles loaded with superparamagnetic iron oxide and sorafenib in vitro

Abstract

Background:The purpose of this study was to evaluate the inhibitory effect of targeted folatefunctionalized micelles containing superparamagnetic iron oxide nanoparticles (SPIONs) and sorafenib on human hepatic carcinoma (HepG2) cells in vitro, and to observe the feasibility of surveillance of this targeting therapeutic effect by magnetic resonance imaging. Methods: Sorafenib and SPIONs were loaded into polymeric micelles. The targeted nanocarrier was synthesized by functionalizing the micelles with folate. Folate-free micelles loaded with sorafenib and SPIONs were used as control (nontargeted) micelles. Uptake of the nanocarrier by cells was assessed using Prussian blue staining after 1 hour of incubation with the polymeric micelles. The inhibitory effect of the targeted micelles on HepG2 cell proliferation at various concentrations of sorafenib was assessed in vitro using the methyl thiazolyl tetrazolium (MTT) assay and apoptotic analysis using flow cytometry. Magnetic resonance imaging using a clinical 1.5 T scanner was performed to detect changes in the signal intensity of cells after incubation with the targeted micelles. Results: Prussian blue staining showed significantly more intracellular SPIONs in cells incubated with the targeted micelles than those incubated with nontargeted micelles. The MTT assay showed that the average inhibitory ratio in the targeted group was significantly higher than that in the nontargeted group (38.13% versus 22.54%, P = 0.028). The mean apoptotic rate in the targeted cells, nontargeted cells, and untreated cells was 17.01%, 11.04%, and 7.89%, respectively. The apoptotic rate in the targeted cells was significantly higher than that in the nontargeted cells (P = 0.043). The T2 signal intensity on magnetic resonance imaging of cells treated with the targeted micelles decreased significantly with increasing concentrations of sorafenib in the cell culture medium, but there was no obvious decrease in signal intensity in cells treated with the nontargeted micelles. Conclusion: Folate-functionalized polymeric micelles loaded with SPIONs and sorafenib inhibited proliferation and induced apoptosis of HepG2 cells in vitro. The inhibitory events caused by targeted micelles can be monitored using clinical magnetic resonance.

GEM-loaded magnetic albumin nanospheres modified with cetuximab for simultaneous targeting, magnetic resonance imaging, and double-targeted thermochemotherapy of pancreatic cancer cells

“…Further, targeted nanospheres have also been proved to be effective drug delivery carriers. Similar to previous studies, 37,38 we also entrapped nanosized signal revealed that AsPC-1 was a high EGFR-expressing cell line, whereas MIA PaCa-2 belongs to a weak expressing cell line. This corresponded well with confirmatory western blot results.…”

Inulin-based polymer coated SPIONs as potential drug delivery systems for targeted cancer therapy

“…Indeed, the presence of a hydrophilic shell avoids hydrophobic-hydrophobic interactions that provoke SPIONs aggregation, so nullifying all advantages related to the nanomeric dimensions of the starting carrier [16]. Many natural and synthetic polymers such as poly(hydroxyethyl) aspartamide derivative [17] and [18], chitosan, ethyl cellulose, poly(lactide) acid, poly(lactide-co-glycolide) acid and poly(ethylene)glycol have been employed as coating agents for enhancing SPIONs stability and conferring surface functional groups available for further reactions [19] and [20]. However, some of these either are not sufficiently bioeliminable or degrade to acidic products often yielding to local inflammation.…”

“…However, some of these either are not sufficiently bioeliminable or degrade to acidic products often yielding to local inflammation. Therefore, new cost-effective polymers provided with excellent biocompatibility and versatility should be synthesized and studied in view of clinical applications [20], [21] and [22]. In this study we propose inulin-based copolymer as coating agent for SPIONs.…”

Formulation Design Facilitates Magnetic Nanoparticle Delivery to Diseased Cells and Tissues

“…Folic acid-conjugated MNPs are a classic example of targeted delivery using MNPs. Folic acid-conjugated MNPs were used to target human nasopharyngeal epidermal carcinoma [72], breast cancer [112] and human hepatic carcinoma [113]. Multifunctional MNPs were produced where core–shell biodegradable magnetite nanospheres were conjugated to doxorubicin through a carboxyl linkage and functionalized with iminodiacetic acid-modified folate to provide tumor-targeting capability [114].…”