Tumor-Homing Peptides as Crucial Component of Magnetic-Based Delivery Systems: Recent Developments and Pharmacoeconomical Perspective.

According to data from the World Health Organization (WHO), cancer is considered to be one of the leading causes of death worldwide, and new therapeutic approaches, especially improved novel cancer treatment regimens, are in high demand. Considering that many chemotherapeutic drugs tend to have poor pharmacokinetic profiles, including rapid clearance and limited on-site accumulation, a combined approach with tumor-homing peptide (THP)-functionalized magnetic nanoparticles could lead to remarkable improvements. This is confirmed by an increasing number of papers in this field, showing that the on-target peptide functionalization of magnetic nanoparticles improves their penetration properties and ensures tumor-specific binding, which results in an increased clinical response. This review aims to highlight the potential applications of THPs in combination with magnetic carriers across various fields, including a pharmacoeconomic perspective.

Pharmaceutical Quality by Design Approach to Develop High-Performance Nanoparticles for Magnetic Hyperthermia.

Magnetic hyperthermia holds significant therapeutic potential, yet its clinical adoption faces challenges. One obstacle is the large-scale synthesis of high-quality superparamagnetic iron oxide nanoparticles (SPIONs) required for inducing hyperthermia. Robust and scalable manufacturing would ensure control over the key quality attributes of SPIONs, and facilitate clinical translation and regulatory approval. Therefore, we implemented a risk-based pharmaceutical quality by design (QbD) approach for SPION production using flame spray pyrolysis (FSP), a scalable technique with excellent batch-to-batch consistency. A design of experiments method enabled precise size control during manufacturing. Subsequent modeling linked the SPION size (6-30 nm) and composition to intrinsic loss power (ILP), a measure of hyperthermia performance. FSP successfully fine-tuned the SPION composition with dopants (Zn, Mn, Mg), at various concentrations. Hyperthermia performance showed a strong nonlinear relationship with SPION size and composition. Moreover, the ILP demonstrated a stronger correlation to coercivity and remanence than to the saturation magnetization of SPIONs. The optimal operating space identified the midsized (15-18 nm) Mn0.25Fe2.75O4 as the most promising nanoparticle for hyperthermia. The production of these nanoparticles on a pilot scale showed the feasibility of large-scale manufacturing, and cytotoxicity investigations in multiple cell lines confirmed their biocompatibility. In vitro hyperthermia studies with Caco-2 cells revealed that Mn0.25Fe2.75O4 nanoparticles induced 80% greater cell death than undoped SPIONs. The systematic QbD approach developed here incorporates process robustness, scalability, and predictability, thus, supporting the clinical translation of high-performance SPIONs for magnetic hyperthermia.

Macrophages-mediated delivery of protoporphyrin for sonodynamic therapy of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by infiltration of inflammatory cells, hyperplasia of synovium, and destruction of the joint cartilage. Owing to the low drug delivery efficiency and limited immunosuppression effect, complete cure for RA remains a formidable challenge. Here, we show that live macrophages (Mφs) carrying protoporphyrin-loaded Fe3O4 nanoparticles can migrate to the RA tissues and inhibit the inflammation by sonodynamic therapy. The inflammation of RA leads to the release of cytokines, which guides the migration of the Mφs into the RA tissues, realizing precise delivery of therapeutics. The following sonodynamic therapy induced by ultrasound and protoporphyrin destructs the proliferating synovial cells and also infiltrated inflammatory cells, demonstrating significant therapeutic effect for RA. Meanwhile, the cytokines and relapse of RA can be remarkably suppressed because of the efficient damage to the resident inflammatory cells.

Ultrasmall Fe3O4 nanoparticles self-assembly induced dual-mode T1/T2-weighted magnetic resonance imaging and enhanced tumor synergetic theranostics.

Individual theranostic agents with dual-mode MRI responses and therapeutic efficacy have attracted extensive interest due to the real-time monitor and high effective treatment, which endow the providential treatment and avoid the repeated medication with side effects. However, it is difficult to achieve the integrated strategy of MRI and therapeutic drug due to complicated synthesis route, low efficiency and potential biosafety issues. In this study, novel self-assembled ultrasmall Fe3O4 nanoclusters were developed for tumor-targeted dual-mode T1/T2-weighted magnetic resonance imaging (MRI) guided synergetic chemodynamic therapy (CDT) and chemotherapy. The self-assembled ultrasmall Fe3O4 nanoclusters synthesized by facilely modifying ultrasmall Fe3O4 nanoparticles with 2,3-dimercaptosuccinic acid (DMSA) molecule possess long-term stability and mass production ability. The proposed ultrasmall Fe3O4 nanoclusters shows excellent dual-mode T1 and T2 MRI capacities as well as favorable CDT ability due to the appropriate size effect and the abundant Fe ion on the surface of ultrasmall Fe3O4 nanoclusters. After conjugation with the tumor targeting ligand Arg-Gly-Asp (RGD) and chemotherapy drug doxorubicin (Dox), the functionalized Fe3O4 nanoclusters achieve enhanced tumor accumulation and retention effects and synergetic CDT and chemotherapy function, which serve as a powerful integrated theranostic platform for cancer treatment.

Model predictive control (MPC) applied to a simplified model, magnetic nanoparticle hyperthermia (MNPH) treatment process.

Magnetic nanoparticle hyperthermia (MNPH) has emerged as a promising cancer treatment that complements conventional ionizing radiation and chemotherapy. MNPH involves injecting iron-oxide nanoparticles into the tumor and exposing it to an alternating magnetic field (AMF). Iron oxide nanoparticles produce heat when exposed to radiofrequency AMF due to hysteresis loss. Minimizing the non-specific heating in human tissues caused by exposure to AMF is crucial. A pulse-width-modulated AMF has been shown to minimize eddy-current heating in superficial tissues. This project developed a control strategy based on a simplified mathematical model in MATLAB SIMULINK®to minimize eddy current heating while maintaining a therapeutic temperature in the tumor. A minimum tumor temperature of 43 [°C] is required for at least 30 [min] for effective hyperthermia, while maintaining the surrounding healthy tissues below 39 [°C]. A model predictive control (MPC) algorithm was used to reach the target temperature within approximately 100 [s]. As a constrained MPC approach, a maximum AMF amplitude of 36 [kA/m] and increment of 5 [kA/m/s] were applied. MPC utilized the AMF amplitude as an input and incorporated the open-loop response of the eddy current heating in its dynamic matrix. A conventional proportional integral (PI) controller was implemented and compared with the MPC performance. The results showed that MPC had a faster response (30 [s]) with minimal overshoot (1.4 [%]) than PI controller (115 [s] and 5.7 [%]) response. In addition, the MPC method performed better than the structured PI controller in its ability to handle constraints and changes in process parameters.

NIR and magnetism dual-response multi-core magnetic vortex nanoflowers for boosting magneto-photothermal cancer therapy.

Due to the relatively low efficiency of magnetic hyperthermia and photothermal conversion, it is rather challenging for magneto-photothermal nanoagents to be used as an effective treatment during tumor hyperthermal therapy. The advancement of magnetic nanoparticles exhibiting a vortex-domain structure holds great promise as a viable strategy to enhance the application performance of conventional magnetic nanoparticles while retaining their inherent biocompatibility. Here, we report the development of Mn0.5Zn0.5Fe2O4 nanoflowers with ellipsoidal magnetic cores, and show them as effective nanoagents for magneto-photothermal synergistic therapy. Comparative studies were conducted on the heating performance of anisometric Mn0.5Zn0.5Fe2O4 (MZF) nanoparticles, including nanocubes (MZF-C), hollow spheres (MZF-HS), nanoflowers consisting of ellipsoidal magnetic cores (MZF-NFE), and nanoflowers consisting of needle-like magnetic cores (MZF-NFN). MZF-NFE exhibits an intrinsic loss parameter (ILP) of up to 15.3 N h m2 kg-1, which is better than that of commercial equivalents. Micromagnetic simulations reveal the magnetization configurations and reversal characteristics of the various MZF shapes. Additionally, all nanostructures displayed a considerable photothermal conversion efficiency rate of more than 18%. Our results demonstrated that by combining the dual exposure of MHT and PTT for hyperthermia treatments induced by MZF-NFE, BT549, MCF-7, and 4T1 cell viability can be significantly decreased by ∼95.7% in vitro.

Feature Matching of Microsecond-Pulsed Magnetic Fields Combined with Fe3O4 Particles for Killing A375 Melanoma Cells.

The combination of magnetic fields and magnetic nanoparticles (MNPs) to kill cancer cells by magneto-mechanical force represents a novel therapy, offering advantages such as non-invasiveness, among others. Pulsed magnetic fields (PMFs) hold promise for application in this therapy due to advantages such as easily adjustable parameters; however, they suffer from the drawback of narrow pulse width. In order to fully exploit the potential of PMFs and MNPs in this therapy, while maximizing therapeutic efficacy within the constraints of the narrow pulse width, a feature-matching theory is proposed, encompassing the matching of three aspects: (1) MNP volume and critical volume of Brownian relaxation, (2) relaxation time and pulse width, and (3) MNP shape and the intermittence of PMF. In the theory, a microsecond-PMF generator was developed, and four kinds of MNPs were selected for in vitro cell experiments. The results demonstrate that the killing rate of the experimental group meeting the requirements of the theory is at least 18% higher than the control group. This validates the accuracy of our theory and provides valuable guidance for the further application of PMFs in this therapy.

Magnetic hyperthermia in cancer therapy, mechanisms, and recent advances: A review.

Hyperthermia therapy refers to the elevating of a region in the body for therapeutic purposes. Different techniques have been applied for hyperthermia therapy including laser, microwave, radiofrequency, ultrasonic, and magnetic nanoparticles and the latter have received great attention in recent years. Magnetic hyperthermia in cancer therapy aims to increase the temperature of the body tissue by locally delivering heat from the magnetic nanoparticles to cancer cells with the aid of an external alternating magnetic field to kill the cancerous cells or prevent their further growth. This review introduces magnetic hyperthermia with magnetic nanoparticles. It includes the mechanism of the operation and magnetism behind the magnetic hyperthermia phenomenon. Different synthesis methods and surface modification to enhance the biocompatibility, water solubility, and stability of the nanoparticles in physiological environments have been discussed. Recent research on versatile types of magnetic nanoparticles with their ability to increase the local temperature has been addressed.

Self-propelling bacteria-based magnetic nanoparticles (BacMags) for targeted magnetic hyperthermia therapy against hypoxic tumors.

Magnetic hyperthermia-based cancer therapy (MHCT) holds great promise as a non-invasive approach utilizing heat generated by an alternating magnetic field for effective cancer treatment. For an efficacious therapeutic response, it is crucial to deliver therapeutic agents selectively at the depth of tumors. In this study, we present a new strategy using the naturally occurring tumor-colonizing bacteria Escherichia coli (E. coli) as a carrier to deliver magnetic nanoparticles to hypoxic tumor cores for effective MHCT. Self-propelling delivery agents, "nano-bacteriomagnets" (BacMags), were developed by incorporating anisotropic magnetic nanocubes into E. coli which demonstrated significantly improved hyperthermic performance, leading to an impressive 85% cell death in pancreatic cancer. The in vivo anti-cancer response was validated in a syngeneic xenograft model with a 50% tumor inhibition rate within 20 days and a complete tumor regression within 30 days. This proof-of-concept study demonstrates the potential of utilizing anaerobic bacteria for the delivery of magnetic nanocarriers as a smart therapeutic approach for enhanced MHCT.

Influence of SPION Surface Coating on Magnetic Properties and Theranostic Profile.

This study aimed to develop multifunctional nanoplatforms for both cancer imaging and therapy using superparamagnetic iron oxide nanoparticles (SPIONs). Two distinct synthetic methods, reduction-precipitation (MR/P) and co-precipitation at controlled pH (MpH), were explored, including the assessment of the coating's influence, namely dextran and gold, on their magnetic properties. These SPIONs were further functionalized with gadolinium to act as dual T1/T2 contrast agents for magnetic resonance imaging (MRI). Parameters such as size, stability, morphology, and magnetic behavior were evaluated by a detailed characterization analysis. To assess their efficacy in imaging and therapy, relaxivity and hyperthermia experiments were performed, respectively. The results revealed that both synthetic methods lead to SPIONs with similar average size, 9 nm. Mössbauer spectroscopy indicated that samples obtained from MR/P consist of approximately 11-13% of Fe present in magnetite, while samples obtained from MpH have higher contents of 33-45%. Despite coating and functionalization, all samples exhibited superparamagnetic behavior at room temperature. Hyperthermia experiments showed increased SAR values with higher magnetic field intensity and frequency. Moreover, the relaxivity studies suggested potential dual T1/T2 contrast agent capabilities for the coated SPpH-Dx-Au-Gd sample, thus demonstrating its potential in cancer diagnosis.

Minimally Invasive Delivery of Percutaneous Ablation Agent via Magnetic Colloidal Hydrogel Injection for Treatment of Hepatocellular Carcinoma.

Percutaneous thermotherapy, a minimally invasive operational procedure, is employed in the ablation of deep tumor lesions by means of target-delivering heat. Conventional thermal ablation methods, such as radiofrequency or microwave ablation, to a certain extent, are subjected to extended ablation time as well as biosafety risks of unwanted overheating. Given its effectiveness and safety, percutaneous thermotherapy gains a fresh perspective, thanks to magnetic hyperthermia. In this respect, an injectable- and magnetic-hydrogel-construct-based thermal ablation agent is likely to be a candidate for the aforementioned clinical translation. Adopting a simple and environment-friendly strategy, a magnetic colloidal hydrogel injection is introduced by a binary system comprising super-paramagnetic Fe3O4 nanoparticles and gelatin nanoparticles. The colloidal hydrogel constructs, unlike conventional bulk hydrogel, can be easily extruded through a percutaneous needle and then self-heal in a reversible manner owing to the unique electrostatic cross-linking. The introduction of magnetic building blocks is exhibited with a rapid magnetothermal response to an alternating magnetic field. Such hydrogel injection is capable of generating heat without limitation of deep penetration. The materials achieve outstanding therapeutic results in mouse and rabbit models. These findings constitute a new class of locoregional interventional thermal therapies with minimal collateral damages.

Magnetic Nanoparticles and Methylprednisolone Based Physico-Chemical Bifunctional Neural Stem Cells Delivery System for Spinal Cord Injury Repair.

Neural stem cells (NSCs) transplantation is an attractive and promising treatment strategy for spinal cord injury (SCI). Various pathological processes including the severe inflammatory cascade and difficulty in stable proliferation and differentiation of NSCs limit its application and translation. Here, a novel physico-chemical bifunctional neural stem cells delivery system containing magnetic nanoparticles (MNPs and methylprednisolone (MP) is designed to repair SCI, the former regulates NSCs differentiation through magnetic mechanical stimulation in the chronic phase, while the latter alleviates inflammatory response in the acute phase. The delivery system releases MP to promote microglial M2 polarization, inhibit M1 polarization, and reduce neuronal apoptosis. Meanwhile, NSCs tend to differentiate into functional neurons with magnetic mechanical stimulation generated by MNPs in the static magnetic field, which is related to the activation of the PI3K/AKT/mTOR pathway. SCI mice achieve better functional recovery after receiving NSCs transplantation via physico-chemical bifunctional delivery system, which has milder inflammation, higher number of M2 microglia, more functional neurons, and axonal regeneration. Together, this bifunctional NSCs delivery system combined physical mechanical stimulation and chemical drug therapy is demonstrated to be effective, which provides new treatment insights into clinical transformation of SCI repair.

Magnetic hybrid nanovesicles for the precise diagnosis and treatment of central nervous system disorders.

INTRODUCTION: Central nervous system (CNS)-related disorders are increasingly being recognized as a global health challenge worldwide. There are significant challenges for effective diagnosis and treatment due to the presence of the CNS barriers which impede the management of neurological diseases. Combination of nanovesicles (NVs) and magnetic nanoparticles (MNPs), referred to as magnetic nanovesicles (MNVs), is now well suggested as a potential theranostic option for improving the management of neurological disorders with increased targeting efficiency and minimized side effects. AREAS COVERED: This review provides a summary of major CNS disorders and the physical barriers limiting the access of imaging/therapeutic agents to the CNS environment. A special focus on the unique features of MNPs and NV is discussed which make them attractive candidates for neuro-nanomedicine. Furthermore, a deeper understanding of MNVs as a promising combined strategy for diagnostic and/or therapeutic purposes in neurological disorders is provided. EXPERT OPINION: The multifunctionality of MNVs offers the ability to overcome the CNS barriers and can be used to monitor the effectiveness of treatment. The insights provided will guide future research toward better outcomes and facilitate the development of next-generation, innovative treatments for CNS disorders.

Precision USPIO-PEG-SLex Nanotheranostic Agent Targeted Photothermal Therapy for Enhanced Anti-PD-L1 Immunotherapy to Treat Immunotherapy Resistance.

Background: The anti-Programmed Death-Ligand 1 (termed aPD-L1) immune checkpoint blockade therapy has emerged as a promising treatment approach for various advanced solid tumors. However, the effect of aPD-L1 inhibitors limited by the tumor microenvironment makes most patients exhibit immunotherapy resistance. Methods: We conjugated the Sialyl Lewis X with a polyethylene glycol-coated ultrasmall superparamagnetic iron oxide (USPIO-PEG) to form UPS nanoparticles (USPIO-PEG-SLex, termed UPS). The physicochemical properties of UPS were tested and characterized. Transmission electron microscopy and ICP-OES were used to observe the cellular uptake and targeting ability of UPS. Flow cytometry, mitochondrial membrane potential staining, live-dead staining and scratch assay were used to verify the in vitro photothermal effect of UPS, and the stimulation of UPS on immune-related pathways at the gene level was analyzed by sequencing. Biological safety analysis and pharmacokinetic analysis of UPS were performed. Finally, the amplification effect of UPS-mediated photothermal therapy on aPD-L1-mediated immunotherapy and the corresponding mechanism were studied. Results: In vitro experiments showed that UPS had strong photothermal therapy ability and was able to stimulate 5 immune-related pathways. In vivo, when the PTT assisted aPD-L1 treatment, it exhibited a significant increase in CD4+ T cell infiltration by 14.46-fold and CD8+ T cell infiltration by 14.79-fold, along with elevated secretion of tumor necrosis factor-alpha and interferon-gamma, comparing with alone aPD-L1. This PTT assisted aPD-L1 therapy achieved a significant inhibition of both primary tumors and distant tumors compared to the alone aPD-L1, demonstrating a significant difference. Conclusion: The nanotheranostic agent UPS has been introduced into immunotherapy, which has effectively broadened its application in biomedicine. This photothermal therapeutic approach of the UPS nanotheranostic agent enhancing the efficacy of aPD-L1 immune checkpoint blockade therapy, can be instructive to address the challenges associated with immunotherapy resistance, thereby offering potential for clinical translation.

Fe3O4SPIONs in cancer theranostics-structure versus interactions with proteins and methods of their investigation.

As the second leading cause of death worldwide, neoplastic diseases are one of the biggest challenges for public health care. Contemporary medicine seeks potential tools for fighting cancer within nanomedicine, as various nanomaterials can be used for both diagnostics and therapies. Among those of particular interest are superparamagnetic iron oxide nanoparticles (SPIONs), due to their unique magnetic properties,. However, while the number of new SPIONs, suitably modified and functionalized, designed for medical purposes, has been gradually increasing, it has not yet been translated into the number of approved clinical solutions. The presented review covers various issues related to SPIONs of potential theranostic applications. It refers to structural considerations (the nanoparticle core, most often used modifications and functionalizations) and the ways of characterizing newly designed nanoparticles. The discussion about the phenomenon of protein corona formation leads to the conclusion that the scarcity of proper tools to investigate the interactions between SPIONs and human serum proteins is the reason for difficulties in introducing them into clinical applications. The review emphasizes the importance of understanding the mechanism behind the protein corona formation, as it has a crucial impact on the effectiveness of designed SPIONs in the physiological environment.

Magnetoactive Composite Conduits Based on Poly(3-hydroxybutyrate) and Magnetite Nanoparticles for Repair of Peripheral Nerve Injury.

Peripheral nerve injury poses a threat to the mobility and sensitivity of a nerve, thereby leading to permanent function loss due to the low regenerative capacity of mature neurons. To date, the most widely clinically applied approach to bridging nerve injuries is autologous nerve grafting, which faces challenges such as donor site morbidity, donor shortages, and the necessity of a second surgery. An effective therapeutic strategy is urgently needed worldwide to overcome the current limitations. Herein, a magnetic nerve guidance conduit (NGC) based on biocompatible biodegradable poly(3-hydroxybutyrate) (PHB) and 8 wt % of magnetite nanoparticles modified by citric acid (Fe3O4-CA) was fabricated by electrospinning. The crystalline structure of NGCs was studied by X-ray diffraction, which indicated an enlarged ß-phase of PHB in the composite conduit compared to a pure PHB conduit. Tensile tests revealed greater ductility of PHB/Fe3O4-CA: the composite conduit has Young's modulus of 221 ± 52 MPa and an elongation at break of 28.6 ± 2.9%, comparable to clinical materials. Saturation magnetization (σs) of Fe3O4-CA and PHB/Fe3O4-CA is 61.88 ± 0.29 and 7.44 ± 0.07 emu/g, respectively. The water contact angle of the PHB/Fe3O4-CA conduit is lower as compared to pure PHB, while surface free energy (σ) is significantly higher, which was attributed to higher surface roughness and an amorphous phase as well as possible PHB/Fe3O4-CA interface interactions. In vitro, the conduits supported the proliferation of rat mesenchymal stem cells (rMSCs) and SH-SY5Y cells in a low-frequency magnetic field (0.67 Hz, 68 mT). In vivo, the conduits were used to bridge damaged sciatic nerves in rats; pure PHB and composite PHB/Fe3O4-CA conduits did not cause acute inflammation and performed a barrier function, which promotes nerve regeneration. Thus, these conduits are promising as implants for the regeneration of peripheral nerves.

Improving tumor treatment through intratumoral injection of drug-loaded magnetic nanoparticles and low-intensity ultrasound.

The intratumoral injection of therapeutic agents responsive to external stimuli has gained considerable interest in treating accessible tumors due to its biocompatibility and capacity to reduce side effects. For the first time, a novel approach is explored to investigate the feasibility of utilizing low-intensity ultrasound in combination with intratumoral injection of drug-loaded magnetic nanoparticles (MNPs) to thermal necrosis and chemotherapy with the objective of maximizing tumor damage while avoiding harm to surrounding healthy tissue. In this study, a mathematical framework is proposed based on a multi-compartment model to evaluate the effects of ultrasound transducer's specifications, MNPs size and distribution, and drug release in response to the tumor microenvironment characteristics. The results indicate that while a higher injection rate may increase interstitial fluid pressure, it also simultaneously enhances the concentration of the therapeutic agent. Moreover, by increasing the power and frequency of the transducer, the acoustic pressure and intensity can be enhanced. This, in turn, increases the impact on accumulated MNPs, resulting in a rise in temperature and localized heat generation. Results have demonstrated that smaller MNPs have a lower capacity to generate heat compared to larger MNPs, primarily due to the impact of sound waves on them. It is worth noting that smaller MNPs have been observed to have enhanced diffusion, allowing them to effectively spread within the tumor. However, their smaller size also leads to rapid elimination from the extracellular space into the bloodstream. To summarize, this study demonstrated that the local injection of MNPs carrying drugs not only enables localized chemotherapy but also enhances the effectiveness of low-intensity ultrasound in inducing tissue thermal necrosis. The findings of this study can serve as a valuable and reliable resource for future research in this field and contribute to the development of personalized medicine.

In situ theranostic platform combining highly localized magnetic fluid hyperthermia, magnetic particle imaging, and thermometry in 3D.

Theranostic platforms, combining diagnostic and therapeutic approaches within one system, have garnered interest in augmenting invasive surgical, chemical, and ionizing interventions. Magnetic particle imaging (MPI) offers a quite recent alternative to established radiation-based diagnostic modalities with its versatile tracer material (superparamagnetic iron oxide nanoparticles, SPION). It also offers a bimodal theranostic framework that can combine tomographic imaging with therapeutic techniques using the very same SPION. Methods: We show the interleaved combination of MPI-based imaging, therapy (highly localized magnetic fluid hyperthermia (MFH)) and therapy safety control (MPI-based thermometry) within one theranostic platform in all three spatial dimensions using a commercial MPI system and a custom-made heating insert. The heating characteristics as well as theranostic applications of the platform were demonstrated by various phantom experiments using commercial SPION. Results: We have shown the feasibility of an MPI-MFH-based theranostic platform by demonstrating high spatial control of the therapeutic target, adequate MPI-based thermometry, and successful in situ interleaved MPI-MFH application. Conclusions: MPI-MFH-based theranostic platforms serve as valuable tools that enable the synergistic integration of diagnostic and therapeutic approaches. The transition into in vivo studies will be essential to further validate their potential, and it holds promising prospects for future advancements.

Recent advances in functionalized ferrite nanoparticles: From fundamentals to magnetic hyperthermia cancer therapy.

Cancers are fatal diseases that lead to most death of human beings, which urgently require effective treatments methods. Hyperthermia therapy employs magnetic nanoparticles (MNPs) as heating medium under external alternating magnetic field. Among various MNPs, ferrite nanoparticles (FNPs) have gained significant attention for hyperthermia therapy due to their exceptional magnetic properties, high stability, favorable biological compatibility, and low toxicity. The utilization of FNPs holds immense potential for enhancing the effectiveness of hyperthermia therapy. The main hurdle for hyperthermia treatment includes optimizing the heat generation capacity of FNPs and controlling the local temperature of tumor region. This review aims to comprehensively evaluate the magnetic hyperthermia treatment (MHT) of FNPs, which is accomplished by elucidating the underlying mechanism of heat generation and identifying influential factors. Based upon fundamental understanding of hyperthermia of FNPs, valuable insights will be provided for developing efficient nanoplatforms with enhanced accuracy and magnetothermal properties. Additionally, we will also survey current research focuses on modulating FNPs' properties, external conditions for MHT, novel technical methods, and recent clinical findings. Finally, current challenges in MHT with FNPs will be discussed while prospecting future directions.

Magnetically navigated microbubbles coated with albumin/polyarginine and superparamagnetic iron oxide nanoparticles.

While microbubbles (MB) are routinely used for ultrasound (US) imaging, magnetic MB are increasingly explored as they can be guided to specific sites of interest by applied magnetic field gradient. This requires the MB shell composition tuning to prolong MB stability and provide functionalization capabilities with magnetic nanoparticles. Hence, we developed air-filled MB stabilized by a protein-polymer complex of bovine serum albumin (BSA) and poly-L-arginine (pArg) of different molecular weights, showing that pArg of moderate molecular weight distribution (15-70 kDa) enabled MB with greater stability and acoustic response while preserving MB narrow diameters and the relative viability of THP-1 cells after 48 h of incubation. After MB functionalization with superparamagnetic iron oxide nanoparticles (SPION), magnetic moment values provided by single MB confirmed the sufficient SPION deposition onto BSA + pArg MB shells. During MB magnetic navigation in a blood vessel mimicking phantom with magnetic tweezers and in a Petri dish with adherent mouse renal carcinoma cell line, we demonstrated the effectiveness of magnetic MB localization in the desired area by magnetic field gradient. Magnetic MB co-localization with cells was further exploited for effective doxorubicin delivery with drug-loaded MB. Taken together, these findings open new avenues in control over albumin MB properties and magnetic navigation of SPION-loaded MB, which can envisage their applications in diagnostic and therapeutic needs.