title: High-performance PEGylated Mn-Zn ferrite nanocrystals as a passive-targeted agent for magnetically induced cancer theranostics.
abstract: An effective magnetic nanocrystals (MNCs)-mediated theranostics strategy as a combination of simultaneous diagnostics and heating treatment of tumors by using magnetic resonance imaging (MRI) and alternating current magnetic field (ACMF) is successfully developed. In this strategy, we had firstly synthesized a well-established Mn-Zn ferrite MNCs coated with PEG-phospholipids (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol copolymers, DSPE-PEG2000). The monodisperse PEGylated MNCs with core-shell structure (15 nm) exhibited excellent performance, such as high magnetism of 98 emu g(-1) Fe, relaxivity coefficient (r2) of 338 mm(-1) s(-1), and specific absorption rate (SAR) value of 324 W g(-1) Fe. It was proved that the obtained MNCs with an average diameter of 48.6 nm can drastically minimize the recognition and phagocytosis of macrophages, simultaneously improve their biocompatibility in vitro. These advantages endowed them with efficient passive targeting ability in vivo for prominent tumor MRI and magnetically induced heating when exposed to ACMF, based on enhanced permeability and retention (EPR) effects. To ensure sufficient accumulation of MNCs within tumors for targeted hyperthermia, we described the use of MNCs with a well-tolerated intravenous single dose of 18 mg Fe/kg mouse body weight, achieving repeatedly injection and hyperthermia within a subcutaneous breast cell carcinoma mouse model. With an ACMF of 12 A at 390 kHz, the tumor surface sites could be heated to approximately 43 °C in 30 min based on MNCs-mediated intravenous injections. The long-lasting hyperthermia could effectively induce the apoptosis of tumor cells, inhibit the angiogenesis of tumor vessels, and finally suppress the tumor growth within a certain period of time.
authors.affiliation: State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, PR China. Electronic address: zhangyu@seu.edu.cn.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Caiyun
authors.initials: C
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, PR China.
authors.forename: Lina
authors.initials: L
authors.lastname: Song
authors.affiliation: Jiangsu Key Laboratory of Molecular and Functional Imaging, Medical School, Southeast University, Nanjing 210009, PR China.
authors.forename: Song
authors.initials: S
authors.lastname: Wen
authors.affiliation: Jiangsu Key Laboratory of Molecular and Functional Imaging, Medical School, Southeast University, Nanjing 210009, PR China.
authors.forename: Fengchao
authors.initials: F
authors.lastname: Zang
authors.affiliation: State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, PR China.
authors.forename: Gong
authors.initials: G
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, PR China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, PR China.
authors.forename: Changzhi
authors.initials: C
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, PR China.
authors.forename: Ning
authors.initials: N
authors.lastname: Gu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D005290:Ferric Compounds / Q000737:chemistry / Q000494:pharmacology*; D060526:Magnetic Fields; D008279:Magnetic Resonance Imaging; D008280:Magnetics; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000628:therapy*; D010743:Phospholipids / Q000737:chemistry / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology
chemical_list: D020099:Coated Materials, Biocompatible; D005290:Ferric Compounds; D010743:Phospholipids; C001215:ferrite; D011092:Polyethylene Glycols
keywords: High-performance; Mn–Zn ferrite nanocrystals; PEGylation; Passive targeting; Theranostics