Emerging trends in the nanomedicine applications of functionalized magnetic nanoparticles as novel therapies for acute and chronic diseases

Abstract

High-quality point-of-care is critical for timely decision of disease diagnosis and healthcare management. In this regard, biosensors have revolutionized the field of rapid testing and screening, however, are confounded by several technical challenges including material cost, half-life, stability, site-specific targeting, analytes specificity, and detection sensitivity that affect the overall diagnostic potential and therapeutic profile. Despite their advances in point-of-care testing, very few classical biosensors have proven effective and commercially viable in situations of healthcare emergency including the recent COVID-19 pandemic. To overcome these challenges functionalized magnetic nanoparticles (MNPs) have emerged as key players in advancing the biomedical and healthcare sector with promising applications during the ongoing healthcare crises. This critical review focus on understanding recent developments in theranostic applications of functionalized magnetic nanoparticles (MNPs). Given the profound global economic and health burden, we discuss the therapeutic impact of functionalized MNPs in acute and chronic diseases like small RNA therapeutics, vascular diseases, neurological disorders, and cancer, as well as for COVID-19 testing. Lastly, we culminate with a futuristic perspective on the scope of this field and provide an insight into the emerging opportunities whose impact is anticipated to disrupt the healthcare industry.

Keywords: Magnetic nanoparticles; Nanomedicine; Neurological disorders; Si-RNA therapeutics; Vascular diseases.

Fig. 1

Functionalization types and features of core magnetic nanoparticles. A Illustration of magnetic nanoparticles prepared with various shells. (Reproduced with permission from Wilczewska et al. [34]). B Illustration for the assembly of various MNP surface functionalization methods. SPION surface coating is achieved via several methods including in situ coating, surface adsorption and end grafting. (Reproduced with permission from Veiseh et al. [18])

Fig. 2

Surface functionalization of core magnetic nanoparticles. A Representative coating types used in iron-oxide core MNP functionalization (IONPs). Grey circles represent the core of IONPs. (Reproduced with permission from Arias et al. [35]). B Schematic for PEG-based MNP surface functionalization. Iron (Ferric hydroxide) based core was first surface coated with oleic acid (OA) and then functionalized with poly ethylene glycol (PEG) containing the N-hydroxysuccinimide (NHS) functional group for increased stability and drug binding. (Reproduced with permission from Yallapu et al. [36])

Fig. 3

The many emerging applications of functionalized MNPs. A Schematic showing various nanomaterial’s including functionalized MNPs in sensing and detection of miRNAs. (Reproduced with permission from Gessner et al. [42]). B Illustration of analytics and biomedical applications of core shell functionalized MNPs. (Reproduced with permission from Anderson et al. [43])

Fig. 4

The many emerging applications of functionalized MNPs. A Application of a multifunctional magnetic core–shell nanoparticle (MCNP) constituting a magnetic zinc-doped iron oxide (ZnFe₂O₄) core nanoparticle surface modified with silica shell, for the dual delivery of miR-let-7a and anticancer drug (doxorubicin) in breast cancer. (Reproduced with permission from Yin et al. [55]). B Magnetic nanoparticle-based microRNA and hyperthermia therapy to enhance the treatment brain cancer. a First, functionalized MNPs are delivered to glioblastoma cells under magnetic field to release miRNA let-7a and induce hyperthermia followed by cellular apoptosis. b Structure and designing of functionalized MNPs with let-7a miRNA with polyethyleneimine (PEI). (Reproduced with permission from Yin et al. [56]). C Synthesis of miR-198 antisense functionalized magnetic for liver cancer: illustrated steps, (i) functionalization of MNP, (ii) cellular uptake; (iii) selective capturing of miR-198 post (iv) cellular lysis, separation, (v) quantification of miR-198. (Reproduced with permission from Gessner et al. [57])

Fig. 5

Functionalized MNPs (SPION, USPIO)-based anatomical imaging of human diseases. Panel 1: Liver imaging. A–D Weighted magnetic resonance imaging of liver hepatocellular carcinoma demarcated with arrows in healthy (A) and in disease (B) standard imaging (C) vs. functionalized SPION-based enhanced (D) imaging of liver metastasis (marked by pointed arrows) in a patient with colorectal cancer. Lymph node imaging. E–H Imaging of lymph nodes in left iliac region in metastatic infiltration before (E, G) and after (F, H) ferumoxtran administration. G Indicates high UPIO macrophage uptake with arrowheads pointing at no metastasis whereas, H presents lack of drug trafficking with persistent metastasis (arrow head). Panel 2: Imaging Inflammation with USPIOs. A Imaging of external, internal carotid artery (ECA, ICA) in atherosclerosis. T2*-weighted MR images prior (center) and after 24 h (right) of administration (i.v.) of functionalized USPIONs. Decreased signal (circled) around the vessel wall at 24 h. B USPIO-based pancreatic imagining in diabetes. MR images showing SPION accumulation in a Type 1 diabetic (T1D) patient vs. healthy individual. Alterations in the pancreatic microvasculature due to insulitis cause leakage of USPIO particles that can be detected in the inflamed tissue by magnetic resonance imaging. C Contrast differences between nanoparticles (functionalized USPION vs. and gadolinium-based) in MRI imaging in multiple sclerosis (MS). Left, multiple hyperintense lesions in the non-contrast-enhanced T2-weighted image. Center, gadolinium-based imaging showing lesions (three arrows). Right, functionalized USPION-based imaging showing six lesions (three additional arrows), highlighting added value for disease diagnosis. Panel 3: MR imaging with SPION magnetic particles. Functionalized circulating SPION (ferucarbotran-based) visualized with anatomical information. A Image showing SPION circulating through the heart. The top and bottom right images indicate presence in inferior vena cava (sagittal, coronal and transverse orientation). B In vivo measurement from a beating mouse heart by MRI and overlaid with traveling wave MPI data. No signal detected at 2150 m post i.v. injection of ferucarbotran-based SPION (yellow box), whereas, grey circle indicates the signal of the marker points. Presence of SPIONS in the artery a leading and targeting to the heart 3700 ms, and at 4400 ms. (Reproduced and adapted with permission from Dadfar et al. [91])

Fig. 6

Magnetic field guided drug delivery via the vasculature and multimodal MRI-based imaging using functionalized MNPs. (Reproduced with permission from Lee et al. [16])

Fig. 7

Multi-application features of functionalized MNPs in therapeutics. A Schematic of dextran-coated functionalized MNP conjugated with near infrared fluorescent dye (Cy5.5), miR-216a mimic, or inhibitor/anti-sense oligo. (Reproduced with permission from Wang et al. [148]). B Functionalized MNPs coated with Lentiviral (LV) vectors used as vehicles for therapeutic targeting in mouse tumor model. Tissue histochemistry results showing stable retention of functionalized LV-MNPs in the tumor tissue. (Reproduced with permission from Borroni et al. [149]). C Functionalized hybrid MNPs for Adenoviral machinery for therapeutic targeting of oncogenic cells expressing chimeric antigen receptors (CAR). (Reproduced with permission from Huh et al. [150])

Fig. 8

Functionalized MNPs for COVID-19. Panel 1: A–C Designing and fabrication of functionalized MNP for SARS-CoV-2 testing. A Schematic of BNF-80 surface modified with protein-A coating and functionalized with viral spike protein antibody to generate functionalized MNP. B Schematic of viral mimic generation by conjugation of SARS-CoV2 spike protein on streptavidin-coated polystyrene beads. C Representative result indicating signal with and without the presence of virus mimic suggestive of specificity and sensitivity of the MNP. (Reproduced with permission from Zhong et al. [10]). Panel 2: A–C Schematic of the poly (amino)-MNP synthesis. a Step 1: reaction of iron-oxide core with aminopropyl triethoxy silane (APTES). b Step 2: poly (amino-ester) is synthesized by the combination of 1,4-butanediol diacrylate + 6-aminocaproic acid in DMSO solution via diacrylate-amine polymerization. c Step 3: the final (amino-magnetic + poly (amino-ester))-functionalized MNP is represented as poly-(amino) NH₂-MNP. (Reproduced with permission from Chacón-Torres et al. [157])