Photoactivated Formation of an Extravascular Dynamic Hydrogel as an Intelligent Blood Flow Regulator to Reprogram the Immunogenic Landscape.

Long-term tumor starvation may be a potential strategy to elevate the antitumor immune response by depriving nutrients. However, combining long-term starvation therapy with immunotherapy often yields limited efficacy due to the blockage of immune cell migration pathways. Herein, an intelligent blood flow regulator (BFR) is first established through photoactivated in situ formation of the extravascular dynamic hydrogel to compress blood vessels, which can induce long-term tumor starvation to elicit metabolic stress in tumor cells without affecting immune cell migration pathways. By leveraging methacrylate-modified nanophotosensitizers (HMMAN) and biodegradable gelatin methacrylate (GelMA), the developed extravascular hydrogel dynamically regulates blood flow via enzymatic degradation. Additionally, aPD-L1 loaded into HMMAN continuously blocks immune checkpoints. Systematic in vivo experiments demonstrate that the combination of immune checkpoint blockade (ICB) and BFR-induced metabolic stress (BIMS) significantly delays the progression of Lewis lung and breast cancers by reshaping the tumor immunogenic landscape and enhancing antitumor immune responses.

Custom-Design of Multi-Stimuli-Responsive Degradable Silica Nanoparticles for Advanced Cancer-Specific Chemotherapy.

Chemotherapy is crucial in oncology for combating malignant tumors but often encounters obatacles such as severe adverse effects, drug resistance, and biocompatibility issues. The advantages of degradable silica nanoparticles in tumor diagnosis and treatment lie in their ability to target drug delivery, minimizing toxicity to normal tissues while enhancing therapeutic efficacy. Moreover, their responsiveness to both endogenous and exogenous stimuli opens up new possibilities for integrating multiple treatment modalities. This review scrutinizes the burgeoning utility of degradable silica nanoparticles in combination with chemotherapy and other treatment modalities. Commencing the elucidation of degradable silica synthesis and degradation mechanisms, emphasis is placed on the responsiveness of these materials to endogenous (e.g., pH, redox reactions, hypoxia, and enzymes) and exogenous stimuli (e.g., light and high-intensity focused ultrasound). Moreover, this exploration delves into strategies harnessing degradable silica nanoparticles in chemotherapy alone, coupled with radiotherapy, photothermal therapy, photodynamic therapy, gas therapy, immunotherapy, starvation therapy, and chemodynamic therapy, elucidating multimodal synergies. Concluding with an assessment of advances, challenges, and constraints in oncology, despite hurdles, future investigations are anticipated to augment the role of degradable silica in cancer therapy. These insights can serve as a compass for devising more efficacious combined tumor treatment strategies.

Bioactivable STING Nanoagonists to Synergize NIR-II Mild Photothermal Therapy Primed Robust and Long-Term Anticancer Immunity.

Pharmacological activation of the stimulator of interferon genes (STING) pathway has become a promising strategy for cancer immunotherapy. However, the insufficient tumorous accumulation, rapid clearance, and short duration of drug efficacy in the tumor microenvironment of small structural STING agonists greatly compromise the therapeutic efficacy. Herein, a tumorous extracellular matrix (ECM) is presented anchoring STING agonist-based photoimmunothernostic nanomedicine (SAPTN) that can be activated by mild-temperature photothermal therapy (mild PTT) induced neutrophilic inflammation. The SAPTN owns second window near-infrared (NIR-II) photonics properties fitting for NIR-II fluorescence and photoacoustic imaging-guided cancer therapy. The aggregates SAPTN targeting to the ECM provide slow and continuous release of potent STING agonists diABZIs. The mild PTT and long-lasting STING agonists released in the ECM synergistically prime systematic, robust, and long-term anticancer immunity. In a tumor model, this approach leads to complete tumor eradication in about 100% of mice with orthotopic breast tumors, and the mice regained tumor-free survival of at least 2 months. In addition, the immune-mediated abscopal effect shows inhibition of the distant solid tumor growth by intratumoral administration of SAPTN with laser irradiation. Overall, this approach represents a generalized photoactivable nanomedicine to prime anticancer immunity for improved cancer theranostics.

Discovery of a Selective and Orally Bioavailable FGFR2 Degrader for Treating Gastric Cancer.

Abnormal activation of fibroblast growth factor receptors (FGFRs) results in the development and progression of human cancers. FGFR2 is frequently amplified or mutated in cancers; therefore, it is an attractive target for tumor therapy. Despite the development of several pan-FGFR inhibitors, their long-term therapeutic efficacy is hindered by acquired mutations and low isoform selectivity. Herein, we report the discovery of an efficient and selective FGFR2 proteolysis-targeting chimeric molecule, LC-MB12, that incorporates an essential rigid linker. LC-MB12 preferentially internalizes and degrades membrane-bound FGFR2 among the four FGFR isoforms; this may promote greater clinical benefits. LC-MB12 exhibits superior potency in FGFR signaling suppression and anti-proliferative activity compared to the parental inhibitor. Furthermore, LC-MB12 is orally bioavailable and shows significant antitumor effects in FGFR2-dependent gastric cancer in vivo. Taken together, LC-MB12 is a candidate FGFR2 degrader for alternative FGFR2-targeting strategies and offers a promising starting point for drug development.

Recent advances of bioresponsive polymeric nanomedicine for cancer therapy.

A bioresponsive polymeric nanocarrier for drug delivery is able to alter its physical and physicochemical properties in response to a variety of biological signals and pathological changes, and can exert its therapeutic efficacy within a confined space. These nanosystems can optimize the biodistribution and subcellular location of therapeutics by exploiting the differences in biochemical properties between tumors and normal tissues. Moreover, bioresponsive polymer-based nanosystems could be rationally designed as precision therapeutic platforms by optimizing the combination of responsive elements and therapeutic components according to the patient-specific disease type and stage. In this review, recent advances in smart bioresponsive polymeric nanosystems for cancer chemotherapy and immunotherapy will be summarized. We mainly discuss three categories, including acidity-sensitive, redox-responsive, and enzyme-triggered polymeric nanosystems. The important issues regarding clinical translation such as reproducibility, manufacture, and probable toxicity, are also commented.

A smart nanoplatform for enhanced photo-ferrotherapy of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. Emerging therapies, such as ferroptosis mediated cancer therapy and phototherapy, offer new opportunities for HCC treatment. The combination of multiple treatments is often more effective than monotherapy, but many of the current treatments are prone to serious side effects, resulting in a serious decline in patients' quality of life. Therefore, the combination therapy of tumor in situ controllable activation will improve the efficacy and reduce side effects for precise treatment of tumor. Herein, we synthesized a GSH-activatable nanomedicine to synergize photothermal therapy (PTT) and ferrotherapy. We utilized a near-infrared dye SQ890 as both an iron-chelating and a photothermal converter agent, which was encapsulated with a GSH-sensitive polymer (PLGA-SS-mPEG), to attain the biocompatible SQ890@Fe nanoparticles (NPs). In the tumor microenvironment (TME), SQ890@Fe NPs showed a GSH-activated photothermal effect that could increase the Fenton reaction rate. Meanwhile, the depletion of GSH could further increase ferroptosis effect. In turn, the increasing radical generated by ferrotherapy could impair the formation of heat shock proteins (HSPs) which could amplify PTT effects by limiting the self-protection mechanism. Overall, the intelligent nanomedicine SQ890@Fe NPs combines ferrotherapy and PTT to enhance the efficacy and safety of cancer treatment through the mutual promotion of the two treatment mechanisms, providing a new dimension for tumor combination therapy.

pH-activated nanoplatform for visualized photodynamic and ferroptosis synergistic therapy of tumors.

To overcome drug resistance and improve precision theranostics for hepatocellular carcinoma (HCC), a nanoplatform with an "off/on" function for multimodality imaging (near-infrared-II (NIR-II) fluorescence imaging, magnetic resonance imaging (MRI), and photoacoustic imaging) and synergistic therapy (photodynamic therapy and ferroptosis) activated by an acidic pH in the tumor microenvironment is proposed. Although many photosensitizers with photodynamic effects have been reported, very few of them have outstanding photodynamic effect and high stability with response to endogenous stimuli capable of NIR-II imaging. Herein, a new amphiphilic photosensitizer SR780 derived from croconaine dye, was developed with satisfactory photodynamic effects and pH-responsive NIR-II imaging. Interestingly, it was deactivated by coordination with Fe3+ (SR780@Fe) and activated during their release under mild acidic condition. Ferroptosis can generate hydroxyl free radical and lipid peroxide, which aggravate the oxidative stress of tumor cells and mediate their death while depleting glutathione (GSH) to enhance photodynamic effect. In situ pH-activatable theranostic nanoplatform, SR780@Fe-PAE-GP, was thus developed by loading SR780@Fe with pH-responsive polymers, modified by a glypican-3 (GPC-3) receptor-targeting peptide. The synergistic antitumor effects were confirmed both in vitro and in vivo, and the tumor inhibition rate of the SR780@Fe-PAE-GP + L treatment group reached 98%.

Treatment of allergic eosinophilic asthma through engineered IL-5-anchored chimeric antigen receptor T cells.

Severe eosinophilic asthma (SEA) is a therapy-resistant respiratory condition with poor clinical control. Treatment efficacy and patient compliance of current therapies remain unsatisfactory. Here, inspired by the remarkable success of chimeric antigen receptor-based cellular adoptive immunotherapies demonstrated for the treatment of a variety of malignant tumors, we engineered a cytokine-anchored chimeric antigen receptor T (CCAR-T) cell system using a chimeric IL-5-CD28-CD3ζ receptor to trigger T-cell-mediated killing of eosinophils that are elevated during severe asthma attacks. IL-5-anchored CCAR-T cells exhibited selective and effective killing capacity in vitro and restricted eosinophil differentiation with apparent protection against allergic airway inflammation in two mouse models of asthma. Notably, a single dose of IL-5-anchored CCAR-T cells resulted in persistent protection against asthma-related conditions over three months, significantly exceeding the typical therapeutic window of current mAb-based treatments in the clinics. This study presents a cell-based treatment strategy for SEA and could set the stage for a new era of precision therapies against a variety of intractable allergic diseases in the future.

Research progress on the mechanism of action of hesperetin in cerebral ischemia: a narrative review.

Background and Objective: Ischemic cerebrovascular disease is one of the main diseases threatening human health and survival and is a commonly occurring disease in neurology. Due to its high disability rate, ischemic cerebrovascular disease is one of the most important diseases to be prevented and treated at present. The risk factors of cerebral ischemia include atherosclerosis, hypertension, hyperlipidemia, and blood viscosity caused by thrombocytosis. After cerebral ischemia, cerebral ischemia-reperfusion injury may be induced by oxidative stress (OS), inflammatory reaction, nitric oxide damage, apoptosis, excitatory amino acid toxicity, calcium (Ca2+) overload, and other mechanisms. Hesperidin is a flavanone compound and is a key component in citrus plants. It is a kind of traditional Chinese medicine extract with high levels of Pericarpium, shell, fruit, and green peel. In recent years, Hesperidin has received great attention, compelling evidence has indicated Hesperidin plays a beneficial role in cerebral ischemia. Methods: We conducted a literature search for published manuscripts hesperidin in ischemia/reperfusion up to December 2021 in common English databases (i.e., PubMed, EMBASE, Web of Science, SpringerLink, Wiley, Cochrane Library) and Chinese databases [Chinese BioMedical Literature Service System (CBM), WANFANG database, China Knowledge Resource Integrated Database (CNKI)]. Key Content and Findings: In this article, we reviewed the mechanisms of action of hesperidin in the treatment of cerebral ischemia, including antioxidant stress, anti-inflammatory reaction, anti-atherosclerosis, anti-thrombosis, anti-apoptosis, and nitric oxide regulation. Conclusions: In this narrative review, Hesperidin exhibits antioxidant stress, anti-platelet aggregation, vasodilation, anti-atherosclerotic, anti-inflammatory, anti-apoptotic, hypolipidemic, anti-tumor, cardiovascular protection, and nitric oxide-release regulatory properties Such a comprehension of the recent progress of hesperidin will help identify biomarkers for diagnosis and therapeutic targets to cerebral ischemia.

Hesperetin ameliorates glioblastoma by inhibiting proliferation, inducing apoptosis, and suppressing metastasis.

Background: Glioblastoma is the most common type of malignant tumor of the brain. Despite substantial improvements in therapy, the 5-year survival rate of patients with glioblastoma remains low. Antitumor drug development has encountered considerable obstacles, which can be attributed to metastasis and the blood-brain barrier (BBB). Hesperetin (HSP), derived from citrus fruits, exhibits several biological properties, including anticancer and anti-inflammatory activities. In addition, in vitro models have shown that HSP can easily cross the BBB. The purpose of the present study was to explore the effects and underlying mechanisms of HSP on glioblastoma cells. Methods: GL261 cell were cultured and treated with different dose HSP. The cell viability was assessed with Cell Counting Kit-8 (CCK-8) assay. The cell apoptosis was determined using an Annexin V/propidine iodide (PI) staining and Hoechst staining and detection assay, cell migration and invasion were observed on GL261 cells using Matrigel-coated Transwells and Wound-Healing assay. The expression of proteins was detected by Western blotting. Results: HSP suppressed cell proliferation and could induce apoptosis, the latter of which might be regulated through the Phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) and nuclear factor-kappa B (NF-κB) pathways. Furthermore, HSP inhibited cell migration and invasion by downregulating the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9, and inhibited epithelial-mesenchymal transition (EMT) by upregulating the expression of E-cadherin while downregulating N-cadherin and vimentin expression. Conclusions: These findings suggest HSP to be an alternative preventive and therapeutic antiglioblastoma drug that may be especially useful for patients with recurrent glioblastoma.

Delivery of triptolide: a combination of traditional Chinese medicine and nanomedicine.

As a natural product with various biological activities, triptolide (TP) has been reported in anti-inflammatory, anti-tumor and anti-autoimmune studies. However, the narrow therapeutic window, poor water solubility, and fast metabolism limit its wide clinical application. To reduce its adverse effects and enhance its efficacy, research and design of targeted drug delivery systems (TDDS) based on nanomaterials is one of the most viable strategies at present. This review summarizes the reports and studies of TDDS combined with TP in recent years, including passive and active targeting of drug delivery systems, and specific delivery system strategies such as polymeric micelles, solid lipid nanoparticles, liposomes, and stimulus-responsive polymer nanoparticles. The reviewed literature presented herein indicates that TDDS is a multifunctional and efficient method for the delivery of TP. In addition, the advantages and disadvantages of TDDS are sorted out, aiming to provide reference for the combination of traditional Chinese medicine and advanced nano drug delivery systems (NDDS) in the future.

Smart NIR-II croconaine dye-peptide for enhanced photo-sonotheranostics of hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is associated with high morbidity and mortality rates. The development of novel nanomaterials represents an important direction for precise HCC theranostics. The combination of photothermal and sonodynamic therapy has provided great benefits for HCC therapy. Theranostic agents in the second near-infrared window (NIR-II, 1000-1700 nm) show great prospects because of their extraordinarily high detection sensitivity, resolution, and deep penetration. Methods: A sharp pH-sensitive self-assembling Glypican-3 (GPC3)-binding peptide (GBP) dye, CR-PEG-GBP, was developed as an intelligent nanoprobe for NIR-II imaging and photoacoustic (PA) imaging-guided photothermal therapy (PTT) and sonodynamic therapy (SDT) of HCC. Results: This small molecule assembled nanoprobe exhibited advantageous properties, such as responding to a decrease in pH (from normal tissue (pH 7.4) to the tumor microenvironment (pH ~6.5)) and aggregating - from small nanoprobes (<20 nm at pH 7.4) - into large nanoparticles (>160 nm at pH 6.5 and >510 nm at pH 5.5) that enables enhanced imaging and therapeutic effects. Because CR-PEG-GBP can self-aggregate in situ in an acidic tumor microenvironment, it shows high tumor accumulation and long tumor retention time, while being excretable from normal tissues and safe. Conclusions: This intelligent self-assembling small molecule strategy provides a simple yet efficient solution for HCC theranostics and may open up new avenues for designing clinically translatable probes for HCC treatment.

Coordinating the Mechanisms of Action of Ferroptosis and the Photothermal Effect for Cancer Theranostics.

Combination therapy based on different mechanisms of cell death has shown promise in tumor therapy. However, when different modalities are integrated, the maximum synergy of the therapeutic effects is often lacking in the design. Herein, we report a cancer theranostic nanomedicine formula developed by considering the mechanisms of action of ferroptosis and the photothermal effect in combination therapy. The croconaine molecule was encapsulated as both a photothermal converter and an iron-chelating agent with BSA, thus leading to biocompatible and stable Cro-Fe@BSA nanoparticles (NPs). The Cro-Fe@BSA NPs in the tumor milieu showed an activated photothermal effect leading to enhanced radical formation owing to the temperature-dependent Fenton reaction kinetics, while radical formation during ferroptosis in turn prevented the heat-induced formation of heat shock proteins and thus the self-protection mechanism of cancer cells in response to heat. The activatable photoacoustic and magnetic resonance imaging performance of the Cro-Fe@BSA NPs also enabled safe and reliable cancer theranostics.

Recent developments in mesoporous polydopamine-derived nanoplatforms for cancer theranostics.

Polydopamine (PDA), which is derived from marine mussels, has excellent potential in early diagnosis of diseases and targeted drug delivery owing to its good biocompatibility, biodegradability, and photothermal conversion. However, when used as a solid nanoparticle, the application of traditional PDA is restricted because of the low drug-loading and encapsulation efficiencies of hydrophobic drugs. Nevertheless, the emergence of mesoporous materials broaden our horizon. Mesoporous polydopamine (MPDA) has the characteristics of a porous structure, simple preparation process, low cost, high specific surface area, high light-to-heat conversion efficiency, and excellent biocompatibility, and therefore has gained considerable interest. This review provides an overview of the preparation methods and the latest applications of MPDA-based nanodrug delivery systems (chemotherapy combined with radiotherapy, photothermal therapy combined with chemotherapy, photothermal therapy combined with immunotherapy, photothermal therapy combined with photodynamic/chemodynamic therapy, and cancer theranostics). This review is expected to shed light on the multi-strategy antitumor therapy applications of MPDA-based nanodrug delivery systems.

Research Progress on the Functions and Mechanism of circRNA in Cisplatin Resistance in Tumors.

Cisplatin is a common chemotherapeutic drug that has been used to treat of numerous tumors, including testicular, lung, bladder, ovarian, liver and head and neck cancers. Although clinical chemotherapy based on cisplatin has shown a remarkable therapeutic effect, the resistance to cisplatin becomes increasingly obvious as a patient uses it for a prolonged period. It not only affects the prognosis of these tumors, but also causes the recurrence of cancer and decreases the overall survival rate. The development of cisplatin resistance involves several mechanisms, including DNA damage repair, ATP-binding cassette (ABC) transporter, autophagy, cancer stem cells (CSCs), epithelial-mesenchymal transition (EMT), and other related signaling pathways. Interestingly, these mechanisms have been found to be influenced by circular RNAs (circRNAs) to regulate tumor proliferation, invasion, chemosensitivity, and other biological behaviors in the tumor microenvironment (TME). In recent years, circRNAs in cisplatin resistance in tumors, especially lung cancer and gastric cancer, have gradually drawn peoples' attention. This review summarizes recent studies on the functions and mechanisms of circRNAs in cisplatin resistance. We emphasize that circRNA can be used as a promising target gene to improve drug resistance and therapeutic efficacy.

Croconaine-based nanoparticles enable efficient optoacoustic imaging of murine brain tumors.

Contrast enhancement in optoacoustic (photoacoustic) imaging can be achieved with agents that exhibit high absorption cross-sections, high photostability, low quantum yield, low toxicity, and preferential bio-distribution and clearance profiles. Based on advantageous photophysical properties of croconaine dyes, we explored croconaine-based nanoparticles (CR780RGD-NPs) as highly efficient contrast agents for targeted optoacoustic imaging of challenging preclinical tumor targets. Initial characterization of the CR780 dye was followed by modifications using polyethylene glycol and the cancer-targeting c(RGDyC) peptide, resulting in self-assembled ultrasmall particles with long circulation time and active tumor targeting. Preferential bio-distribution was demonstrated in orthotopic mouse brain tumor models by multispectral optoacoustic tomography (MSOT) imaging and histological analysis. Our findings showcase particle accumulation in brain tumors with sustainable strong optoacoustic signals and minimal toxic side effects. This work points to CR780RGD-NPs as a promising optoacoustic contrast agent for potential use in the diagnosis and image-guided resection of brain tumors.

Engineered Polymer Nanoplatforms for Targeted Tumor Cells and Controlled Release Cargos to Enhance Cancer Treatment.

Cancer is composed of a series of uncontrollable cells, which finally form tumors to negatively impact the functions of the body and induce other serious diseases, even leading to death. During the last decades, scientists have devoted great efforts to study cancer; however, there are no effective diagnoses and treatments. Nanomaterials have attracted great attention in the biomedical field in recent years, which are widely used as optical imaging probes and delivery systems for cancer therapy. Among the numerous nanomaterials, polymeric nanoparticles occupy a prominent position because of their tunable micro-size, multifunctional surface, prominent biocompatibility and high drug-carrying capacity. These significant advantages of polymeric nanomaterials have significance over the traditional nanomaterials and have become a potential therapy for cancer. In this review, we focus on the applications of polymeric nanoparticles in cancer theranostics, especially as the drug delivery systems for cancer treatment. This review provides an overview on the advancement of synthesis, application of polymeric nanoparticles- based drug delivery systems and highlights the evaluation for cancer therapy.

A hybrid semiconducting organosilica-based O2 nanoeconomizer for on-demand synergistic photothermally boosted radiotherapy.

The outcome of radiotherapy is significantly restricted by tumor hypoxia. To overcome this obstacle, one prevalent solution is to increase intratumoral oxygen supply. However, its effectiveness is often limited by the high metabolic demand for O2 by cancer cells. Herein, we develop a hybrid semiconducting organosilica-based O2 nanoeconomizer pHPFON-NO/O2 to combat tumor hypoxia. Our solution is twofold: first, the pHPFON-NO/O2 interacts with the acidic tumor microenvironment to release NO for endogenous O2 conservation; second, it releases O2 in response to mild photothermal effect to enable exogenous O2 infusion. Additionally, the photothermal effect can be increased to eradicate tumor residues with radioresistant properties due to other factors. This "reducing expenditure of O2 and broadening sources" strategy significantly alleviates tumor hypoxia in multiple ways, greatly enhances the efficacy of radiotherapy both in vitro and in vivo, and demonstrates the synergy between on-demand temperature-controlled photothermal and oxygen-elevated radiotherapy for complete tumor response.

Targeting Neutrophils for Enhanced Cancer Theranostics.

Improving tumor accumulation and delivery efficiency is an important goal of nanomedicine. Neutrophils play a vital role in both chemically mediating inflammatory response through myeloperoxidase (MPO) and biologically promoting metastasis during inflammation triggered by the primary tumor or environmental stimuli. Herein, a novel theranostic nanomedicine that targets both the chemical and biological functions of neutrophils in tumor is designed, facilitating the enhanced retention and sustained release of drug cargos for improved cancer theranostics. 5-hydroxytryptamine (5-HT) is equipped onto nanoparticles (NPs) loaded with photosensitizers and Zileuton (a leukotriene inhibitor) to obtain MPO and neutrophil targeting NPs, denoted as HZ-5 NPs. The MPO targeting property of 5-HT modified NPs is confirmed by noninvasive positron emission tomography imaging studies. Furthermore, photodynamic therapy is used to initiate the inflammatory response which further mediated the accumulation and retention of neutrophil targeting NPs in a breast cancer model. This design renders a greatly improved theranostic nanomedicine for efficient tumor suppression, and more importantly, inhibition of neutrophil-mediated lung metastasis via the sustained release of Zileuton. This work presents a novel strategy of targeting neutrophils for improved tumor theranostics, which may open up new avenues in designing nanomedicine through exploiting the tumor microenvironment.

Early stratification of radiotherapy response by activatable inflammation magnetic resonance imaging.

Tumor heterogeneity is one major reason for unpredictable therapeutic outcomes, while stratifying therapeutic responses at an early time may greatly benefit the better control of cancer. Here, we developed a hybrid nanovesicle to stratify radiotherapy response by activatable inflammation magnetic resonance imaging (aiMRI) approach. The high Pearson's correlation coefficient R values are obtained from the correlations between the T1 relaxation time changes at 24-48 h and the ensuing adaptive immunity (R = 0.9831) at day 5 and the tumor inhibition ratios (R = 0.9308) at day 18 after different treatments, respectively. These results underscore the role of acute inflammatory oxidative response in bridging the innate and adaptive immunity in tumor radiotherapy. Furthermore, the aiMRI approach provides a non-invasive imaging strategy for early prediction of the therapeutic outcomes in cancer radiotherapy, which may contribute to the future of precision medicine in terms of prognostic stratification and therapeutic planning.