Folate-Targeted PEGylated Magnetoliposomes for Hyperthermia-Mediated Controlled Release of Doxorubicin

Abstract

Doxorubicin (DOX) is a chemotherapeutic agent commonly used for the treatment of solid tumors. However, the cardiotoxicity associated with its prolonged use prevents further adherence and therapeutic efficacy. By encapsulating DOX within a PEGylated liposome, Doxil® considerably decreased DOX cardiotoxicity. By using thermally sensitive lysolipids in its bilayer composition, ThermoDox® implemented a heat-induced controlled release of DOX. However, both ThermoDox® and Doxil® rely on their passive retention in tumors, depending on their half-lives in blood. Moreover, ThermoDox® ordinarily depend on invasive radiofrequency-generating metallic probes for local heating. In this study, we prepare, characterize, and evaluate the antitumoral capabilities of DOX-loaded folate-targeted PEGylated magnetoliposomes (DFPML). Unlike ThermoDox®, DOX delivery via DFPML is mediated by the heat released through dynamic hysteresis losses from magnetothermal converting systems composed by MnFe2O4 nanoparticles (NPs) under AC magnetic field excitation—a non-invasive technique designated magnetic hyperthermia (MHT). Moreover, DFPML dismisses the use of thermally sensitive lysolipids, allowing the use of simpler and cheaper alternative lipids. MnFe2O4 NPs and DFPML are fully characterized in terms of their size, morphology, polydispersion, magnetic, and magnetothermal properties. About 50% of the DOX load is released from DFPML after 30 min under MHT conditions. Being folate-targeted, in vitro DFPML antitumoral activity is higher (IC50 ≈ 1 μg/ml) for folate receptor-overexpressing B16F10 murine melanoma cells, compared to MCF7 human breast adenocarcinoma cells (IC50 ≈ 4 μg/ml). Taken together, our results indicate that DFPML are strong candidates for folate-targeted anticancer therapies based on DOX controlled release.

Quercetin‐encapsulated magnetoliposomes: Fabrication, optimization, characterization, and antioxidant studies

“…[32] They can be used in hyperthermic cancer treatment in the presence of an EMF generating heat, which enables nanoparticles or LP lysis or heat-induced pore formation for drug release. [37,38] MLs can selectively target anticancer therapeutics to the tumor site, providing more successful cancer therapy and overcoming the limitations of conventional therapy. [33] MLs are challenging to maintain their stability due to their susceptibility to Fe 2+ -and Fe 3+ -induced membrane peroxidation, which can successfully be prevented by the antioxidant properties of QU.…”

A versatile strategy to construct surface functionalized pH/redox dual stimuli‐responsive nanogels for targeted drug delivery

“…FA-functionalization on nanobiomaterials often brings them enhanced cellular uptake in many cancer cells by facilitating the FA-receptor-mediated endocytosis process. 50,51 In this work, murine melanoma (B16F10) cell line was used to test the in vitro cell proliferation inhibition of FA-functionalized nanogels because it has been shown express high level of FA receptors, 52,53 Meanwhile, normal cell line CHO-K1 with a low-level expression of FA receptors, was used as the negative control. First, the cytotoxicity of P(MAA-PMA)-1 nanogels were evaluated with CHO-K1 and B16F10 cell lines by CCK-8 assay.…”

The Therapeutic Potential of Chemo/Thermotherapy with Magnetoliposomes for Cancer Treatment

“…To generate the necessary magnetic field to increase and control the temperature during the hyperthermia with nanoparticles, there are commercial heat inducers [43], such as the equipment DM 100 system, nB nanoscale Biomagnetics (Zaragoza, Spain) and Mag-neTherm (NanoTherics) (Warrington, United Kingdom) [44][45][46]. All these instruments provide an accurate control of temperature during hyperthermia in cellular cultures and in tumors generated in laboratory animals.…”

“…Using a target for cancer cell receptors in magnetoliposomes is a strategy that has been studied. Cintra et al (2022) reported that folate-target magnetoliposomes loaded with doxorubicin were more cytotoxic for folate receptor overexpression cells [46]. In recent years, the research on magnetoliposomes has increased (Table 2).…”