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Iron oxide nanoparticles (IONPs) have transitioned from conventional magnetic resonance imaging (MRI) contrast agents into structurally programmable combined imaging/treatment tools, leveraging their superparamagnetism, catalytic activity, and surface engineering versatility to achieve spatiotemporal control over drug delivery and immune modulation. Advances in nanofabrication now yield size-optimized aggregates with enhanced tumor accumulation through the enhanced permeability and retention (EPR) effect, while clinically approved formulations like ferumoxytol demonstrate intrinsic immunomodulatory functionality, positioning IONPs as pivotal tools for precision oncology. Conversely, cancer immunotherapy remains limited by the immunosuppressive tumor microenvironment (TME), where cellular suppression via M2-polarized macrophages and regulatory T cells (Tregs) synergizes with physical exclusion from dense extracellular matrices and metabolic sabotage through lactate-driven acidosis. These barriers establish “immune-cold” phenotypes characterized by deficient CD8⁺ T-cell infiltration and tertiary lymphoid structure formation, driving checkpoint inhibitor resistance with sub-30% response rates in solid tumors. To overcome these constraints, IONPs orchestrate multimodal immunotherapeutic strategies: they reprogram suppressive niches by polarizing macrophages toward M1 phenotypes, activate STING pathways, and induce immunogenic ferroptosis; enable precision delivery via magnetic lymph node targeting and cancer cell membrane-mediated homologous tumor homing; and facilitate real-time theranostics through MRI/magnetic particle imaging (MPI)-monitored immune cell trafficking. Preclinical validation confirms synergistic efficacy, with combinatorial regimens achieving over 50% complete tumor regression by converting immunologically cold microenvironments into inflamed states. This review systematically explores cutting-edge IONP-based innovations—spanning immune cell engineering, biohybrid systems, and energy-amplified therapies—that bridge localized tumor eradication with systemic antitumor immunity, while critically evaluating translational barriers for clinical implementation. Graphical abstract

In contemporary medicine, cancer poses a perilous threat to human life, health, and quality of life, remaining a central focus of medical research and clinical practice. Although traditional cancer treatments, such as surgery, chemotherapy, and radiotherapy, have demonstrated some degree of success, they continue to encounter substantial challenges, including incomplete tumor eradication and the occurrence of severe adverse effects. Therefore, there is an urgent need to develop novel cancer treatment strategies characterized by high efficacy, low toxicity, and precise targeting. Photothermal therapy (PTT), as a newly emerging approach, holds considerable promise due to its unique mechanism of action. Upon laser irradiation, PTT utilizes a photothermal agent (PTA) to transform light energy into thermal energy, thereby inducing localized hyperthermia within tumor tissues. This process enables precise ablation of tumor cells while minimizing damage to surrounding healthy tissues. Recent advancements in photothermal agent research have yielded a diverse array of PTAs, and the synergistic integration of PTT with diagnostic and therapeutic techniques has further expanded its therapeutic efficacy and clinical applicability. This paper will provide an overview of the mechanisms underlying PTT, recent progress in photothermal agent development, synergistic theranostic strategies, and combined therapeutic approaches. The aim is to establish a foundation for optimizing PTAs design, elucidating PTT mechanisms, and advancing research on synergistic therapeutic protocols. Ultimately, these endeavors have the potential to result in more effective and safer disease treatments, thereby advancing the translation of photothermal therapy from foundational research to broad clinical application.

The low delivery efficiency of nanoparticles to solid tumors greatly reduces the therapeutic efficacy and safety which is closely related to low permeability and poor distribution at tumor sites. In this work, an “intrinsic plus extrinsic superiority” administration strategy is proposed to dramatically enhance the mean delivery efficiency of nanoparticles in prostate cancer to 6.84% of injected dose, compared to 1.42% as the maximum in prostate cancer in the previously reported study. Specifically, the intrinsic superiority refers to the virus‐mimic surface topology of the nanoparticles for enhanced nano–bio interactions. Meanwhile, the extrinsic stimuli of microbubble‐assisted low‐frequency ultrasound is to enhance permeability of biological barriers and improve intratumor distribution. The enhanced intratumor enrichment can be verified by photoacoustic resonance imaging, fluorescence imaging, and magnetic resonance imaging in this multifunctional nanoplatform, which also facilitates excellent anticancer effect of photothermal treatment, photodynamic treatment, and sonodynamic treatment via combined laser and ultrasound irradiation. This study confirms the significant advance in nanoparticle accumulation in multiple tumor models, which provides an innovative delivery paradigm to improve intratumor accumulation of nanotherapeutics. This work proposes the combination of intrinsic optimization the nanostructure as virus‐mimic surface topology to enhance nano–bio interactions and extrinsic stimuli of microbubble‐assisted low‐frequency ultrasound to vastly improve intratumor permeability and distribution of nanoparticles in multiple cancer models. The multifunctional nanoplatform is capable with trimodal imaging to determine the optimal therapeutic timing, which demonstrates a successful combined anticancer effect.

Recent studies showed that imaging-guided cancer therapeutics have higher success rates so instead of using a single modality, the combination of diagnosis and therapy (theranostic) modalities have simultaneously been employed more often for the cancer treatments. Also, instead of employing single modality, combination of more than one modality for each cancer diagnosis and therapy becomes to be the route for the scientists study in the field of theranostics and applied nanotechnology due to the improved theranostic efficiency. Purpose-oriented fabricated nanoparticles are usually chosen as carriers and contrast agents for those multimodal theranostic systems owing to their unique optoelectronic (optical-electronic) and physical properties. This is a mini review as a general synopsis of the recent applications of nanoparticles as one of the most efficient cancer theranostic agents and future insights for theranostics.

The enormous development of nanomaterials technology and the immediate response of many areas of science, research, and practice to their possible application has led to the publication of thousands of scientific papers, books, and reports. This vast amount of information requires careful classification and order, especially for specifically targeted practical needs. Therefore, the present review aims to summarize to some extent the role of iron oxide nanoparticles in biomedical research. Summarizing the fundamental properties of the magnetic iron oxide nanoparticles, the review’s next focus was to classify research studies related to applying these particles for cancer diagnostics and therapy (similar to photothermal therapy, hyperthermia), in nano theranostics, multimodal therapy. Special attention is paid to research studies dealing with the opportunities of combining different nanomaterials to achieve optimal systems for biomedical application. In this regard, original data about the synthesis and characterization of nanolipidic magnetic hybrid systems are included as an example. The last section of the review is dedicated to the capacities of magnetite-based magnetic nanoparticles for the management of oncological diseases.

Manganese-based MRI contrast agents have recently attracted much attention as an alternative to Gd-based compounds. Various nanostructures have been proposed for potential applications in in vivo diagnostics and theranostics. This review is focused on the discussion of different types of Mn oxide-based nanoparticles (MnxOy NPs) obtained at the +2, +3 and +4 oxidation states for MRI, multimodal imaging or theranostic applications. These NPs show favorable magnetic properties, good biocompatibility, and an improved toxicity profile relative to Gd(III)-based nanosystems, showing that the Mn paramagnetic ions offer advantages for the next generation of nanoscale MRI and theranostic contrast agents. Their potential for enhancing relaxivity and MRI contrast effects is illustrated through discussion of selected examples published in the past decade.

Multifunctional magnetic nanoparticles and derivative nanocomposites have aroused great concern for multimode imaging and cancer synergistic therapies in recent years. Among the rest, functional magnetic iron oxide nanoparticles (Fe O NPs) have shown great potential as an advanced platform because of their inherent magnetic resonance imaging (MRI), biocatalytic activity (nanozyme), magnetic hyperthermia treatment (MHT), photo-responsive therapy and drug delivery for chemotherapy and gene therapy. Magnetic Fe O NPs can be synthesized through several methods and easily surface modified with biocompatible materials or active targeting moieties. The MRI capacity could be appropriately modulated to induce response between and modes by controlling the size distribution of Fe O NPs. Besides, small-size nanoparticles are also desired due to the enhanced permeation and retention (EPR) effect, thus the imaging and therapeutic efficiency of Fe O NP-based platforms can be further improved. Here, we firstly retrospect the typical synthesis and surface modification methods of magnetic Fe O NPs. Then, the latest biomedical application including responsive MRI, multimodal imaging, nanozyme, MHT, photo-responsive therapy and drug delivery, the mechanism of corresponding treatments and cooperation therapeutics of multifunctional Fe O NPs are also be explained. Finally, we also outline a brief discussion and perspective on the possibility of further clinical translations of these multifunctional nanomaterials. This review would provide a comprehensive reference for readers to understand the multifunctional Fe O NPs in cancer diagnosis and treatment.

Cancer theranostics based on glucose oxidase (GOx)-induced starvation therapy has got more and more attention in cancer management. Herein, GOx armed manganese dioxide nanosheets (denoted as MNS-GOx) were developed as cancer nanotheranostic agent for magnetic resonance (MR)/photoacoustic (PA) dual-modal imaging guided self-oxygenation/hyperthermia dually enhanced starvation cancer therapy. The manganese dioxide nanomaterials with different morphologies (such as nanoflowers, nanosheets and nanowires) were synthesized by a biomimetic approach using melanin as a biotemplate. Afterwards, the manganese dioxide nanosheets (MNS) with two sides and large surface area were selected as the vehicle to carry and deliver GOx. The as-prepared MNS-GOx can perform the circular reaction of glucose oxidation and H O decomposition for enhanced starvation therapy. Moreover, the catalytic activity of GOx could be further improved by the hyperthermia of MNS-GOx upon near-infrared laser irradiation. Most intriguingly, MNS-GOx could achieve \"turn-on\" MR imaging and \"turn-off\" PA imaging simultaneously. The theranostic capability of MNS-GOx was evaluated on A375 tumor-bearing mice with all tumor elimination. Our findings integrated molecular imaging and starvation-based synergistic cancer therapy, which provided a new platform for cancer nanotheranostics.

Multimodal imaging unfolds as an innovative approach that synergistically employs a spectrum of imaging techniques either simultaneously or sequentially. The integration of computed tomography (CT), magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT), positron emission tomography (PET), and optical imaging (OI) results in a comprehensive and complementary understanding of complex biological processes. This innovative approach combines the strengths of each method and overcoming their individual limitations. By harmoniously blending data from these modalities, it significantly improves the accuracy of cancer diagnosis and aids in treatment decision-making processes. Nanoparticles possess a high potential for facile functionalization with radioactive isotopes and a wide array of contrast agents. This strategic modification serves to augment signal amplification, significantly enhance image sensitivity, and elevate contrast indices. Such tailored nanoparticles constructs exhibit a promising avenue for advancing imaging modalities in both preclinical and clinical setting. Furthermore, nanoparticles function as a unified nanoplatform for the co-localization of imaging agents and therapeutic payloads, thereby optimizing the efficiency of cancer management strategies. Consequently, radiolabeled nanoparticles exhibit substantial potential in driving forward the realms of multimodal imaging and theranostic applications. This review discusses the potential applications of molecular imaging in cancer diagnosis, the utilization of nanotechnology-based radiolabeled materials in multimodal imaging and theranostic applications, as well as recent advancements in this field. It also highlights challenges including cytotoxicity and regulatory compliance, essential considerations for effective clinical translation of nanoradiopharmaceuticals in multimodal imaging and theranostic applications. Graphical Abstract

Multifunctional nanoplatforms for imaging‐guided synergistic antitumor treatment are highly desirable in biomedical applications. However, anticancer treatment is largely affected by the pre‐existing hypoxic tumor microenvironment (TME), which not only causes the resistance of the tumors to photodynamic therapy (PDT), but also promotes tumorigenesis and tumor progression. Here, a continuous O2 self‐enriched nanoplatform is constructed for multimodal imaging‐guided synergistic phototherapy based on octahedral gold nanoshells (GNSs), which are constructed by a more facile and straightforward one‐step method using platinum (Pt) nanozyme‐decorated metal–organic frameworks (MOF) as the inner template. The Pt‐decorated MOF@GNSs (PtMGs) are further functionalized with human serum albumin‐chelated gadolinium (HSA‐Gd, HGd) and loaded with indocyanine green (ICG) (ICG‐PtMGs@HGd) to achieve a synergistic PDT/PTT effect and fluorescence (FL)/multispectral optoacoustic tomography (MSOT)/X‐ray computed tomography (CT)/magnetic resonance (MR) imaging. The Pt‐decorated nanoplatform endows remarkable catalase‐like behavior and facilitates the continuous decomposition of the endogenous H2O2 into O2 to enhance the PDT effect under hypoxic TME. HSA modification enhances the biocompatibility and tumor‐targeting ability of the nanocomposites. This TME‐responsive and O2 self‐supplement nanoparticle holds great potential as a multifunctional theranostic nanoplatform for the multimodal imaging‐guided synergistic phototherapy of solid tumors. In this research, a tumor environment (TEM)‐responsive and continuous O2 self‐enriched drug delivery platform based on octahedral gold nanoshells (GNSs) using Pt‐decorated metal–organic frameworks (MOF) as inner template is constructed. The obtained nanostructures are further functionalized with human serum albumin‐gadolinium hybrid (HSA‐Gd, HGd) and loaded with indocyanine green (ICG) (ICG‐PtMGs@HGd) to achieve a multimodal imaging guided enhanced photodynamic therapy/photothermal therapy PDT/PTT effect.