Key Magnetized Exosomes for Effective Targeted Delivery of Doxorubicin Against Breast Cancer Cell Types in Mice Model.

Introduction: Exosomes (Exos) are promising drug delivery systems due to their low immunogenicity, minimal toxicity, high biocompatibility, and effective delivery capabilities. However, addressing the cardiotoxicity and other toxic side effects associated with anthracyclines has proven challenging. Methods: In this study, we loaded doxorubicin (Dox) into Exos derived from human placental mesenchymal stem cells (MSCs) and modified them with carboxylated Fe3O4 nanoparticles (NPs) to create an Exo-Dox-NP delivery system. Using an external magnetic force (MF), we regulated the distribution of Exos for targeted Dox delivery in breast cancer treatment. We characterized and determined the drug-loading efficiency of Exo-Dox-NPs, their uptake by tumor cells, and the modulation of drug release. The therapeutic efficacy of Exo-Dox-NPs was evaluated through both in vitro and in vivo anti-tumor experiments. Results: Our results indicated that Exo-Dox-NPs remain stable in the bloodstream while releasing the drug in the acidic environment of tumor cells and their lysosomes. As a drug delivery system, Exo-Dox-NPs enhanced Dox absorption by tumor cells, demonstrating high targeting specificity. Moreover, Exo-Dox-NPs inhibited the migration of breast cancer cells, as confirmed by scratch migration and Transwell Matrigel invasion assays. In vivo experiments confirmed the effective targeting and delivery of Dox to malignant tumors using Exo-Dox-NPs/MFs, with the Exo-Dox-NP/MF formulation exhibiting the most potent anti-tumor activity. Conclusion: The utilization of Exos as carriers for Dox showed promising efficacy in breast cancer management. Carboxylated Fe3O4 NPs demonstrated to be suitable targeting agents, potentially advancing the development of natural nanocarriers for combination cancer therapy.

Iron-based magnetic nanocomplexes for combined chemodynamic and photothermal cancer therapy through enhanced ferroptosis.

Chemodynamic therapy (CDT) guided by Fenton chemistry and iron-containing materials can induce ferroptosis as a prospective cancer treatment method, but the inefficient Fe3+/Fe2+ conversion restricts the monotherapeutic performances. Here, an iron-based nanoplatform (Fe3O4-SRF@FeTA) including a magnetic core and a reductive film is developed for combined CDT and photothermal therapy (PTT) through ferroptosis augmentation. The inner iron oxide core serves as a photothermal transducer, a magnet-responsive module, and an iron reservoir for CDT. The coated Fe3+-tannic acid film (FeTA) provides extra iron and reductants for Fe3+/Fe2+ conversion acceleration, and functions as a door keeper for the pH- and light-responsive release of the embedded ferroptosis inducer sorafenib (SRF). The in vitro results demonstrate that the iron-based nanocomplexes promote the production of lipid peroxide through the amplified Fenton activity, and downregulate glutathione involved in lipid peroxide repair system through the responsively released SRF. Upon accumulation in tumor by magnetic targeting and sequential laser irradiation locoregionally, Fe3O4-SRF@FeTA nanocomplexes present prominent in vivo anticancer efficacy by leveraging PTT and CDT-enhanced ferroptosis.

Precision Treatment of Colon Cancer Using Doxorubicin-Loaded Metal-Organic-Framework-Coated Magnetic Nanoparticles.

Due to the limited efficacy and evident side effects of traditional chemotherapy drugs attributed to their lack of specificity and selectivity, novel strategies are essential for improving cancer treatment outcomes. Here, we successfully engineered Fe3O4 magnetic nanoparticles coated with zeolitic imidazolate framework-8 (ZIF-8). The resulting nanocomposite (Fe3O4@ZIF-8) demonstrates efficient adsorption of a substantial amount of doxorubicin (DOX) due to the porous nature of ZIF-8. The drug-loaded nanoparticles, Fe3O4@ZIF-8/DOX, exhibit significant accumulation at the tumor site in SW620 colon-cancer-bearing mice when guided by an external magnetic field. Within the acidic microenvironment of the tumor, the ZIF-8 framework collapses, releasing DOX and effectively inducing tumor cell death, thereby inhibiting cancer progression while not causing undesired side effects, as confirmed by a variety of in vitro and in vivo characterizations. In comparison to free DOX, Fe3O4@ZIF-8/DOX nanoparticles show superior efficacy in colon cancer treatment. Our findings suggest that Fe3O4@ZIF-8 holds promise as a carrier for small-molecule drug adsorption and its ferromagnetic properties provide drug targeting capabilities, thereby enhancing therapeutic effects on tumors at the same drug dosage. With excellent biocompatibility, Fe3O4@ZIF-8 demonstrates potential as a drug carrier in targeted cancer chemotherapy. Our work suggests that a combination of magnetic targeting and acid-responsiveness holds great promise for advancing targeted cancer therapy in precision nanomedicine.

Potential magnetic drug targeting with magnetite nanoparticles in cancer treatment by enhancer-modifier natural herb and loaded drug.

In the present study, we prepared magnetite nanoparticles (MNPs) loaded with natural Moringa oleifera (M. olf) herb and Epilim (Ep) drug to evaluate the anti-cancerous activity against brain cancer cells. All the samples were prepared via co-precipitation approach modified with different concentrations of M. olf and Ep drug at room temperature. The MNPs loaded with drug and natural herb were studied in terms of crystal structure, morphology, colloidal stability, size distribution, and magnetic properties. Field emission scanning electron microscopy (FESEM) images exhibited the morphologies of samples with spherical shape as well as the particles size of 9 nm for MNPs and up to 23 nm for its composites. The results of vibrating sample magnetometer (VSM) indicated the magnetization saturation (Ms) of 42.510 emu/g for MNPs. This value reduced to 16-35 emu/g upon loading MNPs with different concentrations of M. olf and Ep. Fourier transform infrared spectroscopy (FTIR) indicated the chemical interaction between the Ep, M.olf and MNPs. Brunauer-Emmett-Teller (BET) analysis confirmed the largest surface area for MNPs (422.61 m2/g) which gradually reduced on addition of M. olf and Ep indicating the successful loading. The zeta potential measurements indicated that the MNPs and MNPs loaded with M. olf and Ep are negatively charged and can be dispersed in the suspension. Furthermore, U87 human glioblastoma cell line was used for the in vitro cellular studies to determine the efficacy of synthesized MNPs against cancer cells. The results confirmed the anti-proliferative activity of the MNPs loaded with M. olf and Ep.

Targeted mitigation of neointimal hyperplasia via magnetic field-directed localization of superparamagnetic iron oxide nanoparticle-labeled endothelial progenitor cells following carotid balloon catheter injury in rats.

BACKGROUND: The transplantation of endothelial progenitor cells (EPCs) has been shown to reduce neointimal hyperplasia following arterial injury. However, the efficacy of this approach is hampered by limited homing of EPCs to the injury site. Additionally, the in vivo recruitment and metabolic activity of transplanted EPCs have not been continuously monitored. METHODS: EPCs were labeled with indocyanine green (ICG)-conjugated superparamagnetic iron oxide nanoparticles (SPIONs) and subjected to external magnetic field targeting to enhance their delivery to a carotid balloon injury (BI) model in Sprague-Dawley rats. Magnetic particle imaging (MPI)/ fluorescence imaging (FLI) multimodal in vivo imaging, 3D MPI/CT imaging and MPI/FLI ex vivo imaging was performed after injury. Carotid arteries were collected and analyzed for pathology and immunofluorescence staining. The paracrine effects were analyzed by enzyme-linked immunosorbent assay. RESULTS: The application of a magnetic field significantly enhanced the localization and retention of SPIONs@PEG-ICG-EPCs at the site of arterial injury, as evidenced by both in vivo continuous monitoring and ex vivo by observation. This targeted delivery approach effectively inhibited neointimal hyperplasia and increased the presence of CD31-positive cells at the injury site. Moreover, serum levels of SDF-1α, VEGF, IGF-1, and TGF-ß1 were significantly elevated, indicating enhanced paracrine activity. CONCLUSIONS: Our findings demonstrate that external magnetic field-directed delivery of SPIONs@PEG-ICG-EPCs to areas of arterial injury can significantly enhance their therapeutic efficacy. This enhancement is likely mediated through increased paracrine signaling. These results underscore the potential of magnetically guided SPIONs@PEG-ICG-EPCs delivery as a promising strategy for treating arterial injuries.

Development of bovine serum albumin-modified Fe3O4 embedded in porous α-ketoglutaric acid/chitosan (BSA/Fe3O4@KA/CS): A magnetically targeted hemostatic dressing for deep and irregular wounds.

Severe bleeding from deep and irregular wounds poses a significant challenge in prehospital and surgical settings. To address this issue, we developed a novel chitosan-based hemostatic dressing with a magnetic targeting mechanism using Fe3O4, termed bovine serum albumin-modified Fe3O4 embedded in porous α-ketoglutaric acid/chitosan (BSA/Fe3O4@KA/CS). This dressing enhances hemostasis by magnetically guiding the agent to the wound site. In vitro, the hemostatic efficacy of BSA/Fe3O4@KA/CS is comparable to that of commercial chitosan (Celox™) and is not diminished by the modification. In vivo, BSA/Fe3O4@KA/CS demonstrated superior hemostatic performance and reduced blood loss compared to Celox™. The hemostatic mechanism of BSA/Fe3O4@KA/CS includes the concentration of solid blood components through water absorption, adherence to blood cells, and activation of the endogenous coagulation pathway. Magnetic field targeting is crucial in directing the dressing to deep hemorrhagic sites. Additionally, safety assessments have confirmed the biocompatibility and biodegradability of BSA/Fe3O4@KA/CS. In conclusion, we introduce a novel approach to modify chitosan using magnetic guidance for effective hemostasis, positioning BSA/Fe3O4@KA/CS as a promising candidate for managing various wounds.

Development and characterization of lipid nanocapsules loaded with iron oxide nanoparticles for magnetic targeting to the blood-brain barrier.

Brain drug delivery is severely hindered by the presence of the blood-brain barrier (BBB). Its functionality relies on the interactions of the brain endothelial cells with additional cellular constituents, including pericytes, astrocytes, neurons, or microglia. To boost brain drug delivery, nanomedicines have been designed to exploit distinct delivery strategies, including magnetically driven nanocarriers as a form of external physical targeting to the BBB. Herein, a lipid-based magnetic nanocarrier prepared by a low-energy method is first described. Magnetic nanocapsules with a hydrodynamic diameter of 256.7 ± 8.5 nm (polydispersity index: 0.089 ± 0.034) and a ξ-potential of -30.4 ± 0.3 mV were obtained. Transmission electron microscopy-energy dispersive X-ray spectroscopy analysis revealed efficient encapsulation of iron oxide nanoparticles within the oily core of the nanocapsules. Both thermogravimetric analysis and phenanthroline-based colorimetric assay showed that the iron oxide percentage in the final formulation was 12 wt.%, in agreement with vibrating sample magnetometry analysis, as the specific saturation magnetization of the magnetic nanocapsules was 12% that of the bare iron oxide nanoparticles. Magnetic nanocapsules were non-toxic in the range of 50-300 µg/mL over 72 h against both the human cerebral endothelial hCMEC/D3 and Human Brain Vascular Pericytes cell lines. Interestingly, higher uptake of magnetic nanocapsules in both cell types was evidenced in the presence of an external magnetic field than in the absence of it after 24 h. This increase in nanocapsules uptake was also evidenced in pericytes after only 3 h. Altogether, these results highlight the potential for magnetic targeting to the BBB of our formulation.

Magnetic targeting and pH-microwave dual responsive Janus mesoporous silica nanoparticles for drug encapsulation and delivery.

In this paper, a new Janus-structured nano drug delivery carrier Fe3O4@TiO2&mSiO2was designed and synthesized, which consisted of a spherical head and a closely connected rod. The head was a nanocomposite of core/shell structure with magnetic spinel ferric tetraoxide core and anatase titanium dioxide shell (Fe3O4@TiO2), and the rod was ordered mesoporous silica (mSiO2). The nanocarriers showed excellent magnetic targeting capability (saturation magnetization, 25.18 emu g-1). The core/shell heads endowed the carriers with fine microwave responsiveness. The pore volume of mesoporous nanocarriers was 0.101 cm3g-1, and the specific surface area was 489.0 m2g-1. Anticancer drug doxorubicin could be loaded in the mesoporous of the carriers to form Fe3O4@TiO2&mSiO2-DOX. The drug loading capacity was 10.4%. Fe3O4@TiO2&mSiO2-DOX exhibited acid-sensitive and microwave-sensitive release properties along with good bio-compatibility. Fe3O4@TiO2&mSiO2Janus nanoparticles are expected to be ideal drug carriers.

Bone marrow stem cells with or without superparamagnetic iron oxide nanoparticles as a magnetic targeting tool: Which is better in regeneration of neurolysed facial nerve? An experimental study.

Aim: This study was performed to evaluate neural regenerative capacities of bone marrow stem cells (BMSCs) with or without superparamagnetic iron oxide nanoparticles (SPIONs) as a magnetic targeting tool after neurolysis of the facial nerve (FN) in albino rats. Methods: Thirty-eight male albino rats were selected. Two of them were euthanized for normal FN histology assessment. Thirty-six rats were injected with ethanol in the FN nerve for neurolysis induction and assessed one week post-operatively by eye blinking test. Animals were divided into three groups, each containing twelve rats: Group I (positive control) was injected with Dulbecco Modified Eagle's medium (DMEM-F12), group II was injected with BMSCs in DMEM-F12, and group III was injected with BMSCs in DMEM-F12 with poly l-lysine coated SPIONs (0.5 mmol/mL). Monitoring of SPIONs in the rat's body was carried out by MRI. A circular neodymium magnet N52 (0.57 T, 2 × 5 mm) was placed on each rat in group III just below the right ear at the site of surgery to attract SPIONs labeled BMSCs, left in place for 24 h, and then removed. From each group, six rats were euthanized at the end of the 4th and 8th week of treatment, respectively. The right FN trunks were extracted for routine histological examination using H&E stain. Immunohistochemical examination by anti-S100B was performed to characterize the thickness of the myelin sheath formed by the Schwann cells. Ultra-structural examination was performed to study changes in axons, myelin sheaths, and Schwann cells. Results: Regeneration of nerve fibers, Schwan cells, and myelin sheaths was better in group II than in groups I and III histologically, immunohistochemically, and ultra-structurally. Conclusion: BMSCs alone could ameliorate FN regeneration better than magnetic targeting treatment using BMSCs labeled with SPIONs.

Combined Placental Mesenchymal Stem Cells with Guided Nanoparticles Effective Against Diabetic Nephropathy in Mouse Model.

Background: Diabetic nephropathy (DN) is a prevalent complication of diabetes mellitus and constitutes the primary cause of mortality in affected patients. Previous studies have shown that placental mesenchymal stem cells (PL-MSCs) can alleviate kidney dysfunction in animal models of DN. However, the limited ability of mesenchymal stem cells (MSCs) to home to damaged sites restricts their therapeutic potential. Enhancing the precision of PL-MSCs' homing to target tissues is therefore vital for the success of cell therapies in treating DN. Methods: We developed Fe3O4 coated polydopamine nanoparticle (NP)-internalized MSCs and evaluated their therapeutic effectiveness in a mouse model of streptozotocin- and high-fat diet-induced DN, using an external magnetic field. Results: Our study confirmed that NPs were effectively internalized into PL-MSCs without compromising their intrinsic stem cell properties. The magnetic targeting of PL-MSCs notably improved their homing to the kidney tissues in mice with DN, resulting in enhanced kidney function compared to the transplantation of PL-MSCs alone. Furthermore, the anti-inflammatory and antifibrotic attributes of PL-MSCs played a role in the recovery of kidney function and structure. Conclusion: These results demonstrate that magnetically targeted therapy using PL-MSCs is a promising approach for treating diabetic nephropathy.

Design and development of a magnetic field-enabled platform for delivering polymer-coated iron oxide nanoparticles to breast cancer cells.

The current literature mostly contains relatively vague descriptions of techniques for implementing in vitro magnetic targeting delivery of iron oxide nanoparticles (IONPs), leading to irreproducible processes and incomparable findings. This discrepancy often arises from the varying exposure of IONPs to the non-uniform magnetic field and differences in the concentration of the polymer-coated IONPs. Hence, we meticulously designed and built a system comprising a platform constructed from polyoxymethylene sheets, which securely holds the permanent magnets, and the cell culture plate. We also tailored the preparation process of the IONPs and the in vitro toxicity studies. The inherent characteristics of IONPs are further enhanced by their coating with natural polymers, alginate (Alg) and chitosan (CS).•The design and construction of the platform were carried out using a laser engraving/cutting machine along with graphic design software. The precise locations of the permanent magnets relative to the cell culture plate were determined via a Gaussmeter.•The quantities of the components in the formulation and the method for fabricating the CS/Alg-coated IONPs (CS/Alg-IONPs) were optimized to ensure that the desired physicochemical properties were obtained.•The cultivation and cytotoxicity evaluation of the fabricated CS/Alg-IONPs against MCF-7 breast cancer cells were described.

Preparation and PET/CT imaging of implant directed 68Ga-labeled magnetic nanoporous silica nanoparticles.

BACKGROUND: Implant infections caused by biofilm forming bacteria are a major threat in orthopedic surgery. Delivering antibiotics directly to an implant affected by a bacterial biofilm via superparamagnetic nanoporous silica nanoparticles could present a promising approach. Nevertheless, short blood circulation half-life because of rapid interactions of nanoparticles with the host's immune system hinder them from being clinically used. The aim of this study was to determine the temporal in vivo resolution of magnetic nanoporous silica nanoparticle (MNPSNP) distribution and the effect of PEGylation and clodronate application using PET/CT imaging and gamma counting in an implant mouse model. METHODS: PEGylated and non-PEGylated MNPSNPs were radiolabeled with gallium-68 (68Ga), implementing the chelator tris(hydroxypyridinone). 36 mice were included in the study, 24 mice received a magnetic implant subcutaneously on the left and a titanium implant on the right hind leg. MNPSNP pharmacokinetics and implant accumulation was analyzed in dependence on PEGylation and additional clodronate application. Subsequently gamma counting was performed for further final analysis. RESULTS: The pharmacokinetics and biodistribution of all radiolabeled nanoparticles could clearly be visualized and followed by dynamic PET/CT imaging. Both variants of 68Ga-labeled MNPSNP accumulated mainly in liver and spleen. PEGylation of the nanoparticles already resulted in lower liver uptakes. Combination with macrophage depletion led to a highly significant effect whereas macrophage depletion alone could not reveal significant differences. Although MNPSNP accumulation around implants was low in comparison to the inner organs in PET/CT imaging, gamma counting displayed a significantly higher %I.D./g for the tissue surrounding the magnetic implants compared to the titanium control. Additional PEGylation and/or macrophage depletion revealed no significant differences regarding nanoparticle accumulation at the implantation site. CONCLUSION: Tracking of 68Ga-labeled nanoparticles in a mouse model in the first critical hours post-injection by PET/CT imaging provided a better understanding of MNPSNP distribution, elimination and accumulation. Although PEGylation increases circulation time, nanoparticle accumulation at the implantation site was still insufficient for infection treatment and additional efforts are needed to increase local accumulation.

Combined Ferromagnetic Nanoparticles for Effective Periodontal Biofilm Eradication in Rat Model.

Introduction: The critical challenge for periodontitis therapy is thoroughly eliminating the dental plaque biofilm, particularly penetrating the deep periodontal tissue. Regular therapeutic strategies are insufficient to penetrate the plaque without disturbing the commensal microflora of the oral cavity. Here, we constructed a Fe3O4 magnetic nanoparticle loading minocycline (FPM NPs) to penetrate the biofilm physically and effectively eliminate periodontal biofilm. Methods: In order to penetrate and remove the biofilm effectively, Fe3O4 magnetic nanoparticles were modified with minocycline using a co-precipitation method. The particle size and dispersion of the nanoparticles were characterized by transmission electron microscopy, scanning electron microscopy, and dynamic light scattering. The antibacterial effects were examined to verify the magnetic targeting of FPM NPs. Confocal laser scanning microscopy was employed to check the effect of FPM + MF and develop the best FPM NPs treatment strategy. Additionally, the therapeutic effect of FPM NPs was investigated in periodontitis rat models. The expression of IL-1ß, IL-6, and TNF-α in periodontal tissues was measured by qRT-PCR and Western blot. Results: The multifunctional nanoparticles exhibited intense anti-biofilm activity and good biocompatibility. The magnetic forces could pull FMP NPs against the biofilm mass and kill bacteria deep in the biofilms both in vivo and in vitro. The integrity of the bacterial biofilm is disrupted under the motivation of the magnetic field, allowing for improved drug penetration and antibacterial performance. The periodontal inflammation recovered well after FPM NPs treatment in rat models. Furthermore, FPM NPs could be monitored in real-time and have magnetic targeting potentials. Conclusion: FPM NPs exhibit good chemical stability and biocompatibility. The novel nanoparticle presents a new approach for treating periodontitis and provides experimental support for using magnetic-targeted nanoparticles in clinic applications.

Force-Mediated Endocytosis of Iron Oxide Nanoparticles for Magnetic Targeting of Stem Cells.

Stem cell therapy represents one of the most promising approaches for tissue repair and regeneration. However, the full potential of stem cell therapy remains to be realized. One major challenge is the insufficient homing and retention of stem cells at the desired sites after in vivo delivery. Here, we provide a proof-of-principle demonstration of magnetic targeting and retention of human muscle-derived stem cells (hMDSCs) in vitro through magnetic force-mediated internalization of magnetic iron oxide nanoparticles (MIONs) and the use of a micropatterned magnet. We found that the magnetic force-mediated cellular uptake of MIONs occurs through an endocytic pathway, and the MIONs were exclusively localized in the lysosomes. The intracellular MIONs had no detrimental effect on the proliferation of hMDSCs or their multilineage differentiation, and no MIONs were translocated to other cells in a coculture system. Using hMDSCs and three other cell types including human umbilical vein endothelial cells (HUVECs), human dermal fibroblasts (HDFs), and HeLa cells, we further discovered that the magnetic force-mediated MION uptake increased with MION size and decreased with cell membrane tension. We found that the cellular uptake rate was initially increased with MION concentration in solution and approached saturation. These findings provide important insight and guidance for magnetic targeting of stem cells in therapeutic applications.

Radiosensitising effect of iron oxide-gold nanocomplex for electron beam therapy of melanoma in vivo by magnetic targeting.

Melanoma is a dangerous type of skin cancer sometimes treated with radiotherapy. However, it induces damage to the surrounding healthy tissue and possibly further away areas. Therefore, it is necessary to give a lower dose to the patient with targeted therapy. In this study, the radio-sensitising effect of gold-coated iron oxide nanoparticles on electron beam radiotherapy of a melanoma tumour with magnetic targeting in a mouse model was investigated. Gold-coated iron oxide nanoparticles were prepared in a steady procedure. The melanoma tumour model was induced in mice. Animals were divided into five groups: (1) normal; (2) melanoma; (3) gold-coated iron oxide nanoparticles alone; (4) electron beam radiotherapy; (5) electron beam radiotherapy plus gold-coated iron oxide nanoparticles. The magnet was placed on the tumour site for 2 h. The tumours were then exposed to 6 MeV electron beam radiotherapy for a dose of 8 Gy. Inductively coupled plasma optical emission spectrometry test, hematoxylin and eosin staining, and enzyme-linked immunosorbent assay blood test were also performed. Gold-coated iron oxide nanoparticles with magnetic targeting before electron beam radiotherapy reduced the growth of the tumour compared to the control group. Blood tests did not show any significant toxicity. Deposition of nanoparticles was more in the tumour and spleen tissue and to a lesser extent in the liver, kidney, and lung tissues. The synergistic effect of nanoparticles administered by the intraperitoneal route and then concentrated into the tumour area by application of an external permanent magnet, before delivery of the electron beam radiotherapy improved the overall cancer treatment outcome and prevented metal distribution side effects.

Synthesis of Multi-Stimuli Responsive Fe3O4 Coated with Diamonds Nanocomposite for Magnetic Assisted Chemo-Photothermal Therapy.

Nanodiamonds with magnetic resonance imaging (MRI) and targeted drug delivery to exert combined effects for biomedical applications have been considered to be an urgent challenge. Herein, a novel bio-nanoarchitectonics (Fe3O4@NDs) with simultaneous imaging and therapeutic capacities was fabricated by covalently conjugating nanodiamonds (NDs) with Fe3O4. Fe3O4@NDs exhibited better biocompatibility and excellent photothermal stability with superb photothermal conversion performance (37.2%). Fe3O4@NDs has high doxorubicin (DOX) loading capacity (193 mg/g) with pH and NIR-responsive release characteristics. Fe3O4@NDs loading DOX showed a combined chemo-photothermal inhibitory effect on the tumor cells. Enhanced T2-weighted MRI contrast toward the tumor, with the assistance of a magnetic field, convinced the Fe3O4@NDs gathered in the tumor more efficiently and could be used for MRI-based cancer diagnosis. Our results revealed an effective strategy to achieve a stimuli-sensitive nanoplatform for multifunctional theranostics by the combined action.

Liposomal Iron Oxide Nanoparticles Loaded with Doxorubicin for Combined Chemo-Photothermal Cancer Therapy.

Iron oxide nanoparticle (IONP) possesses unique advantages over other nanoparticles in the use of cancer imaging and therapy. Specifically, it has drawn great attention in the emerging research field of photothermal cancer therapy. Herein, we developed doxorubicin (DOX)-loaded liposomal IONP (Lipo-IONP/DOX) and evaluated in vitro and in vivo their applicability for combined chemo-photothermal cancer therapy. The Lipo-IONP was synthesized by the thin-film evaporation method. The prepared Lipo-IONP was observed as about a 240 nm-sized agglomerate of globular-shaped nanoparticles. The TEM and FT-IR data evidenced the successful formation of liposomal IONP. The superparamagnetic property of the Lipo-IONP was confirmed by the SQUID analysis. The DSC data showed a transition temperature of about 47-48 °C for the mixed lipids composing the Lipo IONP, and the DOX release studies revealed the feasibility of induced burst release of DOX by laser irradiation. The Lipo-IONP/DOX possessed a plasma half-life of 42 min, which could ensure sufficient circulation time for magnetic tumor targeting. The in vivo magnetic targeting enabled a significant increase (6.3-fold) in the tumor accumulation of Lipo-IONP/DOX, leading to greater photothermal effects. Finally, the preliminary efficacy study evidenced the applicability as well as the safety of the Lipo-IONP/DOX for use in combined chemo-photothermal cancer therapy. Overall, the study results demonstrated that the Lipo-IONP/DOX might serve as an effective and safe agent for combined chemo-photothermal cancer therapy.

Magnetic Targeting Nanocarriers Combined with Focusing Ultrasound for Enhanced Intracerebral Hemorrhage Therapy.

Intracerebral hemorrhage (ICH) remains a significant cause of morbidity and mortality around the world, and surgery is still the most direct and effective way to remove ICH. However, the potential risks brought by surgery, such as normal brain tissue damage, post-operative infection, and difficulty in removing deep hematoma, are still the main problems in the surgical treatment of ICH. Activation of the peroxisome proliferator-activated receptor gamma (PPARγ) is reported to show a good therapeutic effect in hematoma clearance. Herein, a magnetic targeting nanocarrier loaded with a PPARγ agonist (15d-PGJ2-MNPs) is synthesized, which could be magnetically targeted and enriched in the area of the hematoma after intravenous injection. Subsequent application of focusing ultrasound (FUS) could enhance drug diffusion, which activates the PPARγ receptors on macrophages around the hematoma for better hematoma clearance. The 15d-PGJ2-MNP treatment alleviates brain injury, accelerates hematoma clearance, attenuates neuroinflammation, reduces brain edema and significantly improves the deficits in sensory and motor function and spatial learning ability in the ICH mouse model. This work proposes an effective magnetic targeting plus FUS method to treat ICH, highlighting its great potential in the treatment of hemorrhagic stroke.

Magnetotactic Bacteria-Based Drug-Loaded Micromotors for Highly Efficient Magnetic and Biological Double-Targeted Tumor Therapy.

Bacteria-mediated cancer therapy has attracted much attention in recent years. However, using magnetotactic bacteria as both a drug carrier and a drug for cancer therapy has never been reported. Herein, we incorporated a photosensitizer chlorin e6 (Ce6) into the M. magneticum strain AMB-1 through a chemical bond or physical blending. A chemical reaction was finally selected for fabricating AMB-1/Ce6 micromotors, as such micromotors exhibited high drug payload and normal bacterial activities. An interesting finding is that AMB-1 is not only an excellent drug carrier but also a unique drug that could inhibit mouse tumor growth. We also, for the first time, demonstrated that AMB-1 is a photosensitizer. Under laser irradiation, micromotors killed cancer cells with high efficiency due to the high-level reactive oxygen species generated by the micromotors. Micromotors could target the hypoxic and normoxic regions in vitro via both the active swimming of AMB-1 and external magnetic field guidance. Micromotors showed high tumor-homing ability owing to the above double targeting mechanisms. After injection with the micromotors followed by magnetic field guidance and laser irradiation, the growth of mouse tumors was significantly inhibited owing to the AMB-1-based biotherapy and phototoxicity of AMB-1 and Ce6. This micromotor-mediated tumor-targeted therapy strategy may be a great platform for treating many types of solid tumors.

Triple functional mild photothermal improves gene editing of PD-L1 for enhanced antitumor immunity.

Traditional photothermal therapy ablates tumor cells by a high temperature (> 50 °C). Although it has shown good anti-tumor effect in animal models, the potential damages to healthy tissues and the unnecessary inflammatory reactions caused by the high temperature have hindered the clinical transitions of traditional photothermal therapy. In this study, we used polydopamine (PDA) as a mild photothermal material and control the maximum temperature below 45 °C, which not only avoided the side effects caused by a high temperature, but also ablated a fraction of tumor cells and produced tumor antigens. Meanwhile, the near-infrared (NIR) light also served as a "switch" to trigger the release of CRISPR/Cas9 RNP from Fe3O4 nanoparticles (Fe3O4 NPs) after their accumulation to tumor sites via magnetic targeting. The triple functional mild photothermal therapy achieved significant PD-L1 gene knockout efficiency in the tumor-bearing mice, reversed the condition of immunosuppression in the tumor microenvironment, led to a higher level of anti-tumor immune responses and effectively inhibited the growth of melanoma. We anticipate that this triple functional mild photothermal therapy would provide a potential new approach for the treatment of malignant tumors.