Table 2.

Studies using magnetic nanoparticles (MNPs) as drug delivery systems for cancer therapy.

MNP (Particle Size) + Surface Modification	Treatment + Cancer Model	Results	Ref
SPIONs (12 nm). SPIONs were coated with a DMSA, MF66, and covalently functionalized with (i) DOX (MF66-DOX), (ii) pseudopeptide NuCant (MF66-N6L), and (iii) with both (MF66-DOX-N6L).	Treatment: DOX + AMF (H = 15.4 kA/m; f = 435 kHz). Cancer model: breast cancer model (BT474 cell line). Female athymic nude mice were subcutaneously injected (on rear backside) with 2.0 × 106 BT474 cells.	The thermo-chemotherapeutic treatment favors the tumor regression in 50% comparatively to control group in vivo (between day 6 and day 17). MF66-DOX-N6L plus hyperthermia application increased their internalization in cancer cells and enhanced in 90% the cytotoxic effect in vitro, comparatively to control group.	[95]
IONPs (112 nm). MnFe2O4 MNPs were synthesized and were encapsulated in PTX loaded thioether-containing ω-hydroxyacid-co-poly(d,l-lactic acid) (TEHA-co-PDLLA).	Treatment: PTX + AMF (25 mT; f = 765 kHz). Cancer model: colorectal cancer model (Caco-2 cell line) + human mesenchymal stem cells derived from adipose tissue.	In vitro experiments showed that NPs were able to sustain PTX release for up 18 days. Moreover, NPs showed great anticancer activity in a dose-dependent manner with low toxicity toward the primary human stem cells derived from adipose tissue.	[96]
IONPs (122 nm). IONPs were modified with a layer of di-carboxylate polyethylene glycol and carboxylate-methoxy polyethylene glycol. Then, IONPs were coated with silica, obtaining PEGylated silica-coated IONs (PS-IONs).	Treatment: DOX + CDDP. Cancer model: breast cancer model (MCF7 cell line); mouse fibroblast cell line (L929).	NPs showed a dual stimuli-triggered release behavior. A release rate of 69% and 84%, for DOX and CDDP, respectively, was measured during the first 30 h in an acidic environment under photothermal conditions. PS-IONs demonstrated potent antitumor activity in vitro, which was significatively enhanced when exposed to low-power near-IR laser irradiation.	[97]
IONPs (non-mentioned). Surface modification is not mentioned.	Treatment: ferumoxytol. Cancer model: mouse mammary tumor virus—polyoma middle T antigen—MMTV-PyMT; MDA-MB-468). Human fibrosarcoma cells (HT1080); murine macrophages (RAW264.7); human dermal fibroblasts (PCS-201-012); human umbilical vein endothelial cells (HUVECs). Female FVB/N were injected with 2.3 × 106 MMTV-PyMT cancer cells.	Ferumoxytil NPs caused tumor growth inhibition by increasing caspase-3 activity. Moreover, macrophages exposed to the NPs enhanced mRNA transcription associated with pro-inflammatory Th1-type responses. In vivo, IONs significantly inhibited the growth of subcutaneous adenocarcinomas compared to controls (tumor size reduction of 53% at day 21), as well as the development of liver metastasis. Additionally, NPs allowed its use as T2-weighted image for tumor imaging.	[98]
IONPs (20 nm). Surface modification is not mentioned.	Treatment: AT. Cancer model: lung cancer model (A549 and H1975) and human normal lung epithelial cells (BEAS2B); mouse normal liver cells (AML12); rat normal liver cells (BRL3A). Male athymic nude mice were subcutaneously injected with 5 × 105 A549 and H1975 into the dorsal flanks.	AT-MNPs demonstrated inhibition in cancer viability (less than 50% viable cells), whilst displaying no toxicity in vivo. AT-MNP treatment intensified the non-small-cell lung cancer apoptosis, activating the caspase-3 route and downregulating the anti-apoptotic proteins Bcl2 and BclXL, in addition to upregulating the proapoptotic Bax and Bad signals.	[99]
SPIONs (165 nm). Surface modification is not mentioned.	Treatment: MTX + AMF (H023.9 kA/m, f = 410 kHz). Cancer model: human bladder cancer cell line (T24). Male SCID (BALB/cJHanHsd-Prkdc) were subcutaneously injected with 2 × 106 T24 cancer cells dorsally between the hindlegs.	The results revealed that the relapse-free destruction of tumors was superior when the combination of chemotherapy and magnetic hyperthermia was used (13 days post-treatment versus 15 days post-treatment under monotherapy). The authors also observed an impairment of proapoptotic signaling, cell survival, and cell cycle pathways.	[100]

SPIONs: superparamagnetic iron oxide nanoparticles; DMSA: dimercaptosuccinic acid; DOX: doxorubicin; AMF: alternating magnetic field; IONPs: iron oxide nanoparticles; MNPs: magnetic nanoparticles; AT: actein; PTX: paclitaxel; CDDP: cisplatin; MTX: methotrexate.