Folic Acid-Conjugated pH and Redox-Sensitive Ellipsoidal Hybrid Magnetic Nanoparticles for Dual-Triggered Drug Release

Abstract

Stimuli-sensitive and multifunctional nanoparticles are highly desirable biomedical materials for triggered and targeted drug delivery applications. Here, we have designed pH-and redox-triggered magnetic lipid−polymer hybrid nanoparticles (MHNPs) with a core− shell structure. This design is composed of a silica-/mesoporous silicacoated ellipsoidal magnetic nanoparticle with multifunctionality: carrying the anticancer drug (doxorubicin, DOX), the cancer cell targeting ligand (folic acid-conjugated poly(ethylene glycol), FA−PEG) polymer, and being coated with a biocompatible pH-/redox-responsive (poly-Lhistidine−poly(ethylene glycol)−lipoic acid; PLH−PEG−LA) polymer. The lipoic acid units of the PLH−PEG−LA shell of the FA-MHNPs were cross-linked using 1,4-dithiothreitol (DTT). When the FA-MHNPs-DOX were exposed to an endolysosomal pH of 5.5 and 10 mM glutathione (GSH), the particles exhibited a very efficient DOX release profile within 24 h. In addition, cytotoxicity, uptake, and apoptosis assays were performed against breast cancer cell lines. These results showed that FA-MHNPs-DOX promote an enhanced uptake and cell morbidity compared to the nontargeted MHNPs-DOX against tested cell lines. Moreover, the FA-MHNPs-DOX exhibited very effective cytotoxicity and also decreased the cell viability through apoptosis against breast cancer cell lines. In conclusion, it can be said that the pH and redox dual-responsive hybrid FA-MHNPs-DOX has a great potential for controlled drug release.

Injectable and Self-Healable pH-Responsive Gelatin–PEG/Laponite Hybrid Hydrogels as Long-Acting Implants for Local Cancer Treatment

“…The DOX loading efficiency (DLE) of LAP nanodisks was evaluated via the measurement of the specific UV absorption band of DOX at 480 nm using the UV–vis spectrophotometer. The DLE of DOX was calculated according to the following equation by using the standard calibration curve of DOX (Figure S2)­ …”

Smart and Multi-Functional Magnetic Nanoparticles for Cancer Treatment Applications: Clinical Challenges and Future Prospects

“…For instance, FA can stimulate cellular internalization of MNPs in active manner [ 283 ]. In vitro studies indicated FA promoted the targeted and controlled release of DOX in a dual release mechanism (pH and redox) [ 284 ] and a redox-responsive mechanism, respectively [ 283 ]. FA is cheap and widely available, has low immunogenicity and toxicity, also it is simple to alter for application as single/dual targeted systems in neoplasm treatment [ 274 , 281 ].…”

Phthalocyanine-Conjugated Glyconanoparticles for Chemo-photodynamic Combination Therapy

“…After incubation, free Dox, free ZnPc-N 3 , and GNPs-ZnPc/Dox were added into the wells and cells were incubated for 4 h. Analysis of at least 10000 cells for each sample was performed on a BD Accuri C6 flow cytometer. MFI determination was described in a previous study , (Figure C, D).…”