Therapeutic Nanoparticles Research Articles

Solid Lipid Nanoparticles: Peculiar Strategy to Deliver Bio-Proactive Molecules.

Novel Drug Delivery Systems (NDDS) provide numerous benefits compared to conventional dosage forms. Poor aqueous solubility, low bioavailability, frequent dosing, and particular hydrophilic lipophilic character of the drug are the biological factors associated with the traditional systems leading to the development of SLNs. For improving the solubility profile, enhancing the bioavailability, and attaining the best possible therapeutic effect of lipid inclined or aqueous inclined drug, formulating solid lipid nanoparticles is the best choice. Solid Lipid Nanoparticles (SLNs) have been projected as a colloidal carrier system with a size of 50-1,000 nm, collectively combining the benefits of other colloidal systems like liposomes, emulsions, etc., for delivering the drug at the target site. High absorption, high stability, and efficient drug packing enhance the pharmacokinetic and pharmacodynamic properties of the packed drug. Solid Lipid Nanoparticles can be developed in different dosage forms and administered via routes such as nasal, rectal, oral, topical, vaginal, ocular, and parenteral. They have higher physicochemical stability and the batch size can be easily scaled up at a low cost. Lipophilic as well as hydrophilic drugs can be easily incorporated into solid lipid nanoparticles. In this manuscript, the authors have reviewed different aspects of solid lipid nanoparticles, major principles behind mechanism methods, recent patents, applications, and therapeutic potentials of solid lipid nanoparticles.

Vitex Agnus‐Castus L. Nanoparticles: Preparation, Characterization and Assessment of Antimicrobial and Anticancer Activity

AbstractThis study was aimed to synthesise antimicrobial and therapeutic silver nanoparticles (AgNPs) by green synthesis method using Vitex agnus‐castus L. (VAC) seed extract. The synthesised VAC seed extract coated AgNPs were characterised by UV‐Vis spectrometry, Zeta analysis and FT‐IR spectrometry. The antifungal, antimicrobial, cytotoxicity by MTT assay, and anticarcinogenic activities on HeLa cells line were investigated. VAC‐AgNPs exhibited high antimicrobial activity against S. aureus with a zone diameter of 11.3±0.6 mm. In addition, the cytotoxicity of VAC‐AgNPs was evaluated using the L929 fibroblast cell line and the HeLa cells line, with AgNPs applied at six different concentrations. At a concentration of 5.0 mM, viability was found to be 47.6 %±4.2 % in L929 fibroblast cells and 39.6 %±7.9 % in HeLa cells, suggesting a potential antiproliferative effect of VAC‐AgNPs on HeLa cancer cells. The IC50 values of VAC‐AgNPs against the HeLa cell line were calculated as 2.94 μg/ml.

Nanoparticles targeting Sialyl-Tn for efficient tyrosine kinase inhibitor delivery in gastric cancer

Gastric cancer (GC) is the fourth leading cause of cancer-related deaths worldwide and, therefore, it is urgent to develop new and more efficient therapeutic approaches. Foretinib (FRT) is an oral multikinase inhibitor targeting MET (hepatocyte growth factor receptor) and RON (recepteur d'origine nantais) receptor tyrosine kinases (RTKs) that has been used in clinical trials for several solid tumors. Targeted uptake of therapeutic polymeric nanoparticles (NPs) represents a powerful approach in cancer cell drug delivery. Previously, a nanodelivery system composed of polymeric NPs functionalized with B72.3 antibody, which targets the tumor-associated antigen Sialyl-Tn (STn), has been developed. Herein, these NPs were loaded with FRT to evaluate its capacity in delivering the drug to multicellular tumors spheroids (MCTS) and mouse models. The data indicated that B72.3 functionalized FRT-loaded PLGA-PEG-COOH NPs (NFB72.3) specifically target gastric MCTS expressing the STn glycan (MKN45 SimpleCell (SC) cells), leading to a decrease in phospho-RTKs activation and reduced cell viability. In vivo evaluation using MKN45 SC xenograft mice revealed that NFB72.3 were able to decrease tumor growth, reduce cell proliferation and tumor necrosis. NFB72.3-treated tumors also showed inactivation of phospho-MET and phospho-RON. This study demonstrates the value of using NPs targeting STn for FRT delivery, highlighting its potential as a therapeutic application in GC. Statement of significanceDespite the advances in gastric cancer therapeutics, it remains one of the diseases with the highest incidence and mortality in the world. Combining targeted therapies with a controlled drug release is an attractive strategy to reduce drug cytotoxic effects and improve specific drug delivery efficiency to the cancer cells. Thus, we developed nanoparticles loaded with a tyrosine kinase inhibitor and targeting a specific tumor glycan exclusive of cancer cells. In in vivo gastric cancer xenograft mice models, these nanoparticles efficiently reduced tumor growth, cell proliferation and tumor necrosis area and inactivated phosphorylation of targeting receptors. This approach represents an innovative therapeutic strategy with high impact in gastric cancer.

LMAP-18 ADAPTING LASER INTERSTITIAL THERMAL THERAPY (LITT) FOR TREATMENT OF INTRACRANIAL LESIONS IN CANINES

Abstract Malignant gliomas are devastating intracranial tumors with dismal prognoses that impose unique therapeutic challenges. Treatment options include surgical resection, radiation, and chemotherapy, but efficacy is limited and carries associated morbidity. Promise persists for newer modalities, such as immune-based platforms, but the blood-brain barrier (BBB) restricts intracranial therapeutic access, limiting success. Laser interstitial thermal therapy (LITT) is a minimally invasive surgical intervention permitting thermal ablation of brain tumors and other intracranial lesions. During LITT, a laser probe is stereotactically introduced through a small skull burr hole into the lesion. Continuous MRI is used to conduct real-time temperature monitoring via software-based calculation of cumulative thermal dosage zones. LITT is not only capable of ablating neoplastic tissue, but can also open the BBB in peritumoral regions, and thus may synergize with other emerging therapies. We adapted a commercially available LITT system (Monteris Medical) for use in dogs with intracranial lesions. Canine cadavers were used to optimize LITT procedures before employing this platform in live dogs. Our approach consists of 1. obtaining volumetric, T1-weighted, MRI studies to plan trajectories to intracranial targets, 2. fixing canine patients to a surgical bed and registering them for surface matching to a volume rendered image, 3. using an integrated instrument holder (Varioguide, Brainlab) to guide drilling of 4.5 mm skull burr holes for placement of self-tapping titanium “mini-bolts” (Monteris Medical), and 4. introducing the laser catheter probe through the mini-bolts for lesion ablation in the MRI suite. This method allows for rigid stereotaxy, successful neuronavigation, and a minimally invasive approach. We have successfully performed LITT on four canine patients with spontaneously occurring intracranial gliomas and plan to treat additional canine patients with intracranial lesions. Future studies will explore combination therapeutic platforms, including immunotherapy and gold nanoparticles to improve the efficiency and specificity of tumor ablation.

Anti-PEG IgM production induced by PEGylated liposomes as a function of administration route.

Modifying the surface of nanoparticles with polyethylene glycol (PEG) is a commonly used approach for improving the in vitro stability of nanoparticles such as liposomes and increasing their circulation half-lives. We have demonstrated that, in certain conditions, an intravenous (i.v.) injection of PEGylated liposomes (PEG-Lip) induced anti-PEG IgM antibodies, which led to rapid clearance of second doses in mice. SARS-CoV-2 vaccines, composed of mRNA-containing PEGylated lipid nanoparticles, have been widely administered as intramuscular (i.m.) injections, so it is important to determine if PEGylated formulations can induce anti-PEG antibodies. If the favorable properties that PEGylation imparts to therapeutic nanoparticles are to be widely applicable this should apply to various routes of administration. However, there are few reports on the effect of different administration routes on the in vivo production of anti-PEG IgM. In this study, we investigated anti-PEG IgM production in mice following i.m., intraperitoneal (i.p.) and subcutaneous (s.c.) administration of PEG-Lip. PEG-Lip appeared to induce anti-PEG IgM by all the tested routes of administration, although the lipid dose causing maximum responses varied. Splenectomy attenuated the anti-PEG IgM production for all routes of administration, suggesting that splenic immune cells may have contributed to anti-PEG IgM production. Interestingly, in vitro experiments indicated that not only splenic cells but also cells in the peritoneal cavity induced anti-PEG IgM following incubation with PEG-Lip. These observations confirm previous experiments that have shown that measurable amounts of PEG-Lip administered i.p., i.m. or s.c. are absorbed to some extent into the blood circulation, where they can be distributed to the spleen and/or peritoneal cavity, and are recognized by B cells, triggering anti-PEG IgM production. The results obtained in this study have important implications for developing efficient PEGylated nanoparticular delivery system.

Controlled spatial characteristics of ligands on nanoparticles: Determinant of cellular functions

Interactions of various ligands and receptors have been extensively investigated because they regulate a series of signal transduction leading to various functional cellular outcomes. The receptors on cell membrane recognize their specific ligands, resulting in specific binding between ligands and receptors. Accumulating evidence reveals that the receptors recognize the difference on the spatial characteristics of ligands as well as the types of ligands. Thus, control on spatial characteristics of multiple ligands presented on therapeutic nanoparticles is believed to impact the cellular functions. Specifically, the localized and multivalent distribution of ligands on nanoparticles can induce receptor oligomerization and receptor clustering, controlling intensity or direction of signal transduction cascades. Here, we will introduce recent studies on the use of material-based nanotechnology to control spatial characteristics of ligands and their effect on cellular functions. These therapeutic nanoparticles with controlled spatial characteristics of ligands may be a promising strategy for maximized therapeutic outcome.

Self-template synthesis of mesoporous and biodegradable Fe3O4 nanospheres as multifunctional nanoplatform for cancer therapy

Superparamagnetic Fe3O4 nanospheres have demonstrated great potential as important components in nanomedicine for cancer imaging and therapy. One of the major obstacles that impedes their application is the slow degradation of ingested Fe3O4 nanospheres, which potentially causes long-term health risks. To tackle this issue, we proposed to fabricate Fe3O4 nanospheres with mesoporous structure via a simple self-template etching method. The mesoporous Fe3O4 nanospheres not only offered large specific surface area and weak-acidic responsive degradability, but also exhibited T2-weighted magnetic resonance contrast enhancement and magnetic targeting, which made them possible to serve as excellent cancer therapeutic nanoplatform. Both inorganic photothermal therapeutic Au nanoparticles and organic chemotherapeutic doxorubicin hydrochloride were demonstrated to be successfully loaded onto such kind of nanoplatform, and the hybrid nanomedicine demonstrated synergistic photothermal and chemotherapeutic activity for tumor elimination under near infrared irradiation and improved biodegradability in weak acidic tumor microenvironment. We believe that this study paved a simple way for designing multifunctional Fe3O4-based biodegradable nanomedicine.

Epidermal growth factor alters silica nanoparticle uptake and improves gold-nanoparticle-mediated gene silencing in A549 cells.

Delivery of therapeutic nanoparticles (NPs) to cancer cells represents a promising approach for biomedical applications. A key challenge for nanotechnology translation from the bench to the bedside is the low amount of administered NPs dose that effectively enters target cells. To improve NPs delivery, several studies proposed NPs conjugation with ligands, which specifically deliver NPs to target cells via receptor binding. One such example is epidermal growth factor (EGF), a peptide involved in cell signaling pathways that control cell division by binding to epidermal growth factor receptor (EGFR). However, very few studies assessed the influence of EGF present in the cell environment, on the cellular uptake of NPs. We tested if the stimulation of EGFR-expressing lung carcinomacells A549 with EGF affects the uptake of 59 nm and 422 nm silica (SiO2) NPs. Additionally, we investigated whether the uptake enhancement can be achieved with gold NPs, suitable to downregulate the expression of cancer oncogene c-MYC. Our findings show that EGF binding to its receptor results in receptor autophosphorylation and initiate signaling pathways, leading to enhanced endocytosis of 59 nm SiO2 NPs, but not 422 nm SiO2 NPs. Additionally, we demonstrated an enhanced gold (Au) NPs endocytosis and subsequently a higher downregulation of c-MYC. These findings contribute to a better understanding of NPs uptake in the presence of EGF and that is a promising approach for improved NPs delivery.

Green Nanoparticles in Sustainable Therapeutics and Future Sustainability

Green nanoparticles (GNPs) are being produced from microbial and plant sources and have numerous applications in various fields. The article focuses on the NPs that provide various focal points in the many scientific and technological fields for the cutting-edge uses of nanoparticles. Due to their toxicity, cost-effectiveness, ease of use, and environmental friendliness, green NPs are extremely important. It is closely observed how important green NPs are to the development of science and technology in the context of sustainable therapeutics. The only issue with green nanoparticles is occasionally how toxic they can be. A sustainable future, which the entire world looks forward to, is directly related to green nanoparticles and their role in numerous applications.

Remodeling the tumor microenvironment by vascular normalization and GSH-depletion for augmenting tumor immunotherapy

Remodeling tumor microenvironment (TME) is a very promising and effective strategy to enhance the effects of chemotherapy, photodynamic therapy, and immunotherapy. Normalization of tumor vasculature as well as depletion of glutathione (GSH) can improve the TME. Here, we developed a novel therapeutic nanoparticle functional enzyme ultra QDAU5 nanoparticles (FEUQ Nps) based on a fluorescence-on and releasable strategy by combining a vascular normalization inducer, a GSH depleting agent, and an activated fluorophore. In which the cleavage of disulfide bonds releases active molecules that induce vascular normalization and improve the hypoxic microenvironment. In addition, it may deplete GSH in cancer cells, thus inducing the production of reactive oxygen species (ROS) and lipid peroxide (LPO) and promoting iron toxicity. It may also lead to endoplasmic stress and release of calmodulin, which activates the immune system. Meanwhile, quenched fluorophores are turned on in the presence of galactosidase (GLU) for tumor-specific labeling. In summary, we developed novel therapeutic agent nanoparticles with the function of vascular normalization inducers to achieve specific labeling of hepatocellular carcinoma while exerting efficient antitumor effects in vivo.

Morphologic design of nanogold carriers for a carbonic anhydrase inhibitor: Effect on ocular retention and intraocular pressure

Morphologic design of nanomaterials for a diversity of biomedical applications is of increasing interest. The aim of the current study is to construct therapeutic gold nanoparticles of different morphologies and investigate their effect on ocular retention and intraocular pressure in a glaucoma rabbit model. Poly(lactic-co-glycolic acid) (PLGA)-coated nanorods and nanospheres have been synthesized and loaded with carbonic anhydrase inhibitor (CAI), and characterized in vitro for their size, zeta potential and encapsulation efficiency. Nanosized PLGA-coated gold nanoparticles of both morphologies demonstrated high entrapment efficiency (˃ 98%) for the synthesized CAI and the encapsulation of the drug into the developed nanoparticles was confirmed via Fourier transform-infrared spectroscopy. In vivo studies revealed a significant reduction in intraocular pressure upon instillation of drug-loaded nanogold formulations compared to the marketed eye drops. Spherical nanogolds exhibited a superior efficacy compared to the rod-shaped counterparts, probably due to the enhanced ocular retention of spherical nanogolds within collagen fibers of the stroma, as illustrated by transmission electron microscopy imaging. Normal histological appearance was observed for the cornea and retina of the eyes treated with spherical drug-loaded nanogolds. Hence, incorporation of a molecularly-designed CAI into nanogold of tailored morphology may provide a promising strategy for management of glaucoma.

Self‐Immolative Amphiphilic Poly(ferrocenes) for Synergistic Amplification of Oxidative Stress in Tumor Therapy

AbstractAmphiphilic self‐immolative polymers (SIPs) can achieve complete degradation solely through one triggerable event, which potentially optimize the blood clearance and uncontrollable/inert degradability for therapeutic nanoparticles. Herein, we report self‐immolative amphiphilic poly(ferrocenes), BPnbs‐Fc, composed by self‐immolative backbone and aminoferrocene (AFc) side chains as well as end‐capping poly(ethylene glycol) monomethyl ether. Upon triggering by tumor acidic milieu, the BPnbs‐Fc nanoparticles readily degrade to release azaquinone methide (AQM) moieties, which can rapidly deplete intracellular glutathione (GSH) to cascade release AFc. Furthermore, both AFc and its product Fe2+ can catalyze intracellular hydrogen peroxide (H2O2) into highly reactive hydroxyl radicals (⋅OH), thus amplifying the oxidative stress of tumor cells. Rational synergy of GSH depletion and ⋅OH burst can efficiently inhibit tumor growth by the SIPs in vitro and in vivo. This work provides an elegant design to adopt innate tumor milieu‐triggerable SIPs degradation to boost cellular oxidative stress, which is a promising candidate for precision medicine.

Self-Immolative Amphiphilic Poly(ferrocenes) for Synergistic Amplification of Oxidative Stress in Tumor Therapy.

Amphiphilic self-immolative polymers (SIPs) can achieve complete degradation solely through one triggerable event, which potentially optimize the blood clearance and uncontrollable/inert degradability for therapeutic nanoparticles. Herein, we report self-immolative amphiphilic poly(ferrocenes), BPnbs-Fc, composed by self-immolative backbone and aminoferrocene (AFc) side chains as well as end-capping poly(ethylene glycol) monomethyl ether. Upon triggering by tumor acidic milieu, the BPnbs-Fc nanoparticles readily degrade to release azaquinone methide (AQM) moieties, which can rapidly deplete intracellular glutathione (GSH) to cascade release AFc. Furthermore, both AFc and its product Fe2+ can catalyze intracellular hydrogen peroxide (H2O2) into highly reactive hydroxyl radicals (·OH), thus amplifying the oxidative stress of tumor cells. Rational synergy of GSH depletion and ·OH burst can efficiently inhibit tumor growth by the SIPs in vitro and in vivo. This work provides an elegant design to adopt innate tumor milieu-triggerable SIPs degradation to boost cellular oxidative stress, which is a promising candidate for precision medicine.

Endothelial Cell Selectivity to Nanoparticles Depends on Mechanical Phenotype

AbstractEndothelial cells (ECs) elongate in the direction of blood flow, are stiffer, and are considered atheroprotective in areas of the vasculature where flow‐induced shear stress is high and unidirectional and are softer, atherogenic, and polygonal in areas experiencing oscillatory multidirectional flow. To understand the precise roles of EC mechanics and morphology in the uptake of therapeutic nanoparticles (NPs) by atherogenic endothelium, human aortic ECs are induced to adopt prescribed shapes and areas imposed by microcontact patterned adhesive islands. NP uptake per cell increases with increasing spreading area and decreases with increasing cell aspect ratio at constant cell spreading area. Biomechanical analysis shows that elongated cells exhibit higher cellular stress and stiffer membranes than cells with low aspect ratios, indicating a strong correlation between morphology, mechanical phenotype, and NP uptake. Further, ECs elongated by high laminar shear endocytosed NPs to a far lesser extent than those that are nonelongated in the chaotic, lower shear areas when cocultured in the same chamber. Results indicate that conditions leading to atherogenesis, such as low, chaotic shear‐induction of EC polygonal morphology may be used to increase the uptake of therapeutic NPs as a preventative measure against atherosclerosis.

Nanoparticles in NAFLD therapeutics.

Nanoparticles in NAFLD therapeutics.

Messenger RNA rescues medium-chain acyl-CoA dehydrogenase deficiency in fibroblasts from patients and a murine model.

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is the most common inherited disorder of mitochondrial fatty acid β-oxidation (FAO) in humans. Patients exhibit clinical episodes often associated with fasting. Symptoms include hypoketotic hypoglycemia and Reye-like episodes. With limited treatment options, we explored the use of human MCAD (hMCAD) mRNA in fibroblasts from patients with MCAD deficiency to provide functional MCAD protein and reverse the metabolic block. Transfection of hMCAD mRNA into MCAD- deficient patient cells resulted in an increased MCAD protein that localized to mitochondria, concomitant with increased enzyme activity in cell extracts. The therapeutic hMCAD mRNA-lipid nanoparticle (LNP) formulation was also tested in vivo in Acadm-/- mice. Administration of multiple intravenous doses of the hMCAD mRNA-LNP complex (LNP-MCAD) into Acadm-/- mice produced a significant level of MCAD protein with increased enzyme activity in liver, heart and skeletal muscle homogenates. Treated Acadm-/- mice were more resistant to cold stress and had decreased plasma levels of medium-chain acylcarnitines compared to untreated animals. Furthermore, hepatic steatosis in the liver from treated Acadm-/- mice was reduced compared to untreated ones. Results from this study support the potential therapeutic value of hMCAD mRNA-LNP complex treatment for MCAD deficiency.

Broadband Optical Properties of Bi2Se3.

Materials with high optical constants are of paramount importance for efficient light manipulation in nanophotonics applications. Recent advances in materials science have revealed that van der Waals (vdW) materials have large optical responses owing to strong in-plane covalent bonding and weak out-of-plane vdW interactions. However, the optical constants of vdW materials depend on numerous factors, e.g., synthesis and transfer method. Here, we demonstrate that in a broad spectral range (290-3300 nm) the refractive index n and the extinction coefficient k of Bi2Se3 are almost independent of synthesis technology, with only a ~10% difference in n and k between synthesis approaches, unlike other vdW materials, such as MoS2, which has a ~60% difference between synthesis approaches. As a practical demonstration, we showed, using the examples of biosensors and therapeutic nanoparticles, that this slight difference in optical constants results in reproducible efficiency in Bi2Se3-based photonic devices.

Virus-Like Particle-Encapsulated Doxorubicin Enters and Kills Murine Tumor Cells Differently from Free Doxorubicin.

The use of nanoparticles as chemotherapeutic carriers has been suggested as a way to overcome a range of side effects associated with classical cancer treatment such as poor selectivity and tumor resurgence. Obtaining precise control of the size and shape of therapeutic nanoparticles is crucial to optimize the targeting of tumor sites. In this work, it is shown that a previously developed system of polypeptide encapsulating individual DNA molecules, that forms rod-shaped nanoparticles of precisely controlled aspect ratio, can be loaded with the DNA-intercalating chemotherapeutic drug doxorubicin (DOX). It is characterized the size and shape of the DOX loaded-Virus-Like DNA Particles (DOX-VLDP) and shownthat in this system the DOX payload does not leak out. Through in vitro cell studies, it is shown that DOX-VLDP is internalized by melanoma tumor cells (B16F10 cells) in a delayed and endocytosis-dependent way culminating in increased cytotoxicity and selectivity to tumor cells in comparison with free DOX. In addition, it is found that DOX-VLDP trigger apoptosis and autophagy pathways in treated cells. Taken together, the data on the DOX-VLDP nanoparticles shows that they kill cancer cells differently from free DOX.

Intra-articular nanoparticles based therapies for osteoarthritis and rheumatoid arthritis management.

Osteoarthritis (OA) and rheumatoid arthritis (RA) are chronic and progressive inflammatory joint diseases that affect a large population worldwide. Intra-articular administration of various therapeutics is applied to alleviate pain, prevent further progression, and promote cartilage regeneration and bone remodeling in both OA and RA. However, the effectiveness of intra-articular injection with traditional drugs is uncertain and controversial due to issues such as rapid drug clearance and the barrier afforded by the dense structure of cartilage. Nanoparticles can improve the efficacy of intra-articular injection by facilitating controlled drug release, prolonged retention time, and enhanced penetration into joint tissue. This review systematically summarizes nanoparticle-based therapies for OA and RA management. Firstly, we explore the interaction between nanoparticles and joints, including articular fluids and cells. This is followed by a comprehensive analysis of current nanoparticles designed for OA/RA, divided into two categories based on therapeutic mechanisms: direct therapeutic nanoparticles and nanoparticles-based drug delivery systems. We highlight nanoparticle design for tissue/cell targeting and controlled drug release before discussing challenges of nanoparticle-based therapies for efficient OA and RA treatment and their future clinical translation. We anticipate that rationally designed local injection of nanoparticles will be more effective, convenient, and safer than the current therapeutic approach.

Magnetic Response Combined with Bioactive Ion Therapy: A RONS-Scavenging Theranostic Nanoplatform for Thrombolysis and Renal Ischemia-Reperfusion Injury.

Currently, the limited efficacy of antithrombotic treatments is attributed to the inadequacy of pure drugs and the low ability of drugs to target the thrombus site. More importantly, timely thrombolysis is essential to reduce the sequelae of cardiovascular disease, but ischemia-reperfusion injury (IRI) remains a major challenge that must be solved after blood flow recovery. Herein, a multifunctional therapeutic nanoparticle (NP) based on Fe3O4 and strontium ions encapsulated in mesoporous polydopamine was successfully constructed and then loaded with TNK-tPA (FeM@Sr-TNK NPs). The NPs (59.9 min) significantly prolonged the half-life of thrombolytic drugs, which was 3.04 times that of TNK (19.7 min), and they had good biological safety. The NPs were shown to pass through vascular models with different inner diameters, curvatures, and stenosis under magnetic targeting and to enable accurate diagnosis of thrombi by photoacoustic imaging. NPs combined with the magnetic hyperthermia technique were used to accelerate thrombolysis and quickly open blocked blood vessels. Then, renal IRI-induced functional metabolic disorder and tissue damage were evidently attenuated by scavenging toxic reactive oxygen and nitrogen species and through the protective effects of bioactive ion therapy, including reduced apoptosis, increased angiogenesis, and inhibited fibrosis. In brief, we constructed a multifunctional nanoplatform for integrating a "diagnosis-therapy-protection" approach to achieve comprehensive management from thrombus to renal IRI, promoting the advancement of related technologies.