Development of Folate‐Superparamagnetic Nanoconjugates for Inhibition of Cancer Cell Proliferation

Abstract

are widely employed for treating ovarian cancer. [1] Nevertheless, anticancer agents have potential side effects such as hair loss, infertility, diarrhea, and nausea. [2,3] To minimize these side effects, various types of controlled drug delivery systems have been engineered to specifically target the drug to cancer cells based on cells surface receptors interactions in order to avoid toxicity toward normal cells. [4,5] Superparamagnetic iron oxide nanoparticles (SPIONs) have been developed extensively due to their wide spectrum of applications in the biomedical field, including biosensors, [6,7] tissue engineering, [8] drug delivery, [9,10] and in medical science for magnetic resonance imaging (MRI). [11,12,13] Another interesting property deals with the fact that they can generate heat upon application of a local high frequency alternating magnetic field (HAMF). The latter is particularly interesting when considering the cancer therapy as the tumors cannot survive heating up to 45 °C. [14] Furthermore, due to their nanosize, SPIONs can easily play with the enhanced permeability and retention (EPR) effect to be delivered to the solid tumor. [15] Moreover, their surface can be easily modified both to specifically direct a cargo Here, a versatile strategy to engineer smart theranostic nanocarriers is reported. The core/shell nanosystem is composed of a superparamagnetic iron oxide (Fe 3−δ O 4 ) nanoparticle (NP) core bearing the biocompatible thermo-responsive poly(2-(2-methoxy)ethyl methacrylate-oligo(ethylene glycol methacrylate), P(MEO 2 MA x -OEGMA 100−x ) copolymer (where x and 100-x represent the molar fractions of MEO 2 MA and OEGMA, respectively). Folic acid (FA) is end-conjugated to the P(MEO 2 MA x -OEGMA 100−x ) copolymer, leading to Fe 3 − δ O 4 @P(MEO 2 MA x -OEGMA 100−x )-FA, to facilitate active targeting of NPs to cancer cells. A highly potent hydrophobic anticancer agent doxorubicin (DOX) is incorporated in the thermo-responsive P(MEO 2 MA x -OEGMA y ) brushes via supramolecular interactions to increase its solubility and the assessment of therapeutic potentials. These experiments confirm the magnetic hyperthermia properties of nanocarrier and reveal that only a small amount (10% ± 4%) of DOX is diffused at room temperature, while almost full drug (100%) is released after 52 h at 41 °C. Interestingly, it is found that P(MEO 2 MA 60 -OEGMA 40 ) polymers offer to NPs a promising stealth behavior against Human Serum Albumin and Fibrinogen model proteins.

The Effect of Copolymer-Based Nanoparticle Composition (MEO2MA-OEGMA) on the Release Profile of Doxorubicin In Vitro

“…The models used for our system included the zero-order, first-order, Higuchi, and Korsmeyer-Peppas release models. By fitting the data to these models, we aimed to determine the most relevant model that described the drug release behavior [25,26].…”

The Effect of copolymer-Based Nanoparticle Composition (MEO₂MA-OEGMA) on The Release Profile of Doxorubicin In Vitro

“…The models used for our system included the zero-order, first-order, Higuchi, and Korsmeyer-Peppas release models. By fitting the data to these models, we aimed to determine the most relevant model that describes the drug release behavior [20], [21].…”

Liquid-Metal Core–Shell Particles Coated with Folate and Phospholipids for Targeted Drug Delivery and Photothermal Treatment of Cancer Cells

“…On the other hand, no drug release occurred from LM-FA particles that were not irradiated with NIR. Recently, a drug delivery system targeting the folate receptor is being studied, and based on the above results [29], we have produced particles that have DOX delivery powder specifically for cancer cells. (Figure S4).…”