Glioblastoma (GBM) recurrence, driven by therapeutic resistance and diffuse infiltration, remains a critical clinical challenge, fundamentally sustained by a mitochondrial metabolic addiction. To leverage this, we developed a biomimetic nanoplatform (HM-NPs@CM) camouflaged with cancer cell-mitochondria hybrid membranes. This ensures efficient blood-brain barrier traversal and precise mitochondria-targeted co-delivery of sonosensitizer Ce6 and mitophagy inhibitor Mdivi-1 within orthotopic GBM. Upon ultrasound activation, the nanoplatform executes a synergistic ‘Attack-and-Trap’ strategy: sonodynamic therapy (SDT) launches a targeted oxidative assault, while concurrent pharmacological inhibition of mitophagy traps irreparably damaged mitochondria. This accumulation of damaged mitochondria triggers a lethal pathological cascade, where mitochondrial oxidative stress progresses into severe intracellular oxidative stress, culminating in irreversible lytic cell death and sustained cytosolic mtDNA leakage. The liberated mtDNA robustly activates the cGAS-STING pathway, driving Type I interferon synthesis and transforming tumor cells into immunogenic reservoirs. Subsequently, this severe oxidative stress forces the terminal rupture of the plasma membrane, orchestrating the massive release of pre-synthesized immune effectors and damage-associated molecular patterns (DAMPs). Capitalizing on these signals, combination with anti-PD-L1 blockade potently induces dendritic cell maturation and CD8+ T cell infiltration, significantly suppressing tumor growth. Ultimately, this multimodal strategy establishes durable immunological memory, providing comprehensive protection against tumor rechallenge and post-surgical recurrence.

Although heat can enhance the immunogenicity of tumors, inhomogeneous temperature distribution in deep-seated regions often leads to insufficient thermal exposure, resulting in limited antigen release and low immunogenicity. Herein, we designed microwave-sensitizing nanomotors that activate propulsion to break through biological barriers and the deep-seated delivery of heat and immune adjuvants to activate the immune response. Specifically, this nanomotor features a core of dendritic silica (DS) asymmetrically modified with bovine serum albumin-stabilized manganese dioxide nanoparticles (MnO2@BSA) to form the DMB structure. Subsequently, the immune adjuvant R837 and tetradecanol were loaded to obtain the final microwave-sensitizing nanomotors, DMBR. Oxygen (O2) bubbles generated from the catalytic decomposition of H2O2 by the heterostructured MnO2@BSA propel the nanomotors to actively break through these biological barriers autonomously toward deep-seated tumor cells. Furthermore, microwave irradiation accelerates the production of O2 bubbles, enhancing the nanomotor's movement efficiency. In vitro and in vivo studies demonstrated a 3-fold improvement of DMB. Moreover, the DMBR nanomotors promote the enhancement of heat dissemination, R837 delivery efficiency, and localized release of O2 into deep tumor areas. Consequently, a robust immune response is triggered, as evidenced by an increased level of T cell infiltration, leading to significant suppression of both primary and distant tumors. This work presents a sequential barrier-overcoming nanomotor strategy for effective microwave thermal immunotherapy.

Prostate cancer (PCa) is a heterogeneous disease ranging from indolent to highly aggressive forms (e.g., castration-resistant PCa). Although multiparametric MRI plays an important role in the routine diagnosis and management of PCa, emerging challenges underscore a critical unmet need in the era of precision and personalized medicine. Given that metabolic reprogramming is a hallmark of PCa, metabolic imaging techniques that focus on and target changes in metabolic pathways, such as PET and hyperpolarized (HP) 13C MRI, represent critical tools for facilitating early diagnosis, risk stratification, and monitoring of PCa treatment. This review discusses the metabolic characteristics of PCa, the current landscape of MR-based metabolic imaging techniques, and their applications to PCa, with a particular emphasis on recent advances in proton magnetic resonance spectroscopy imaging (1H-MRSI), HP 13C MRI, and other emerging advanced MRI techniques, including chemical exchange saturation transfer (CEST) MRI, sodium (23Na) MRI, and deuterium metabolic imaging (DMI). Additionally, we discuss the challenges and future perspectives for their further clinical translation.

Imatinib resistance in gastrointestinal stromal tumors (GISTs) represents a significant therapeutic challenge. While current research focuses on KIT and PDGFRA genes, the mechanisms underlying resistance remain inadequately understood. This study aims to uncover novel genetic targets and mechanisms to overcome imatinib resistance, with a particular emphasis on MCM2, identified as a crucial factor in this resistance process. We engineered a biomimetic nanoscale microbubble (TMB@TDN-iRGD-siMCM2) utilizing GISTs-T1 cell membranes and lipid components. This system integrates siMCM2 and iRGD with tetrahedral DNA (TDN) to form a versatile platform, validated through polyacrylamide gel electrophoresis and atomic force microscopy. Characterization of the platform’s morphology, size, and zeta potential was conducted, and cellular uptake was assessed using confocal microscopy and flow cytometry. The efficacy of the ultrasound-mediated TMB@TDN-iRGD-siMCM2 platform combined with imatinib was evaluated in vitro and in a murine GISTs tumor model, with subsequent analysis of biodistribution and toxicity. The TMB@TDN-iRGD-siMCM2 platform effectively reversed imatinib resistance in GISTs when mediated by ultrasound. It demonstrated key properties including enhanced penetration, drug stability, and tumor targeting. The system significantly increased imatinib sensitivity and suppressed tumor growth while maintaining a favorable safety profile. This ultrasound-mediated biomimetic platform introduces a novel and efficient strategy for precise gene regulation in GISTs, markedly boosting imatinib’s anti-tumor efficacy. It holds considerable promise for advancing the treatment of GISTs and other solid tumors.

Background:Recently, multiparametric magnetic resonance imaging (mpMRI) and multiparametric ultrasound (mpUS) have been developed to improve prostate cancer (PCa) detection. This study aimed to investigate practice patterns and perceptions among clinicians regarding the use of mpMRI and mpUS as well as prostatic biopsies for PCa diagnosis. Methods:We conducted a national survey via an online questionnaire among urologists, radiologists, and sonographers. The survey collected information on participants' knowledge, routine practices, and perceptions of prostate mpMRI and mpUS, as well as prostatic biopsies. Univariable and multivariable logistic regression analyses were used to identify specialists' characteristics associated with survey responses. Results:There were 354 responses from 144 hospitals were received. The majority (71.4%) of participants performed mpMRI for PCa diagnosis, while a small proportion (15.3%) of them used mpUS. The transperineal ultrasound-guided approach for systematic prostate biopsy was considered as preferable (47.2%). For targeted biopsy, cognitive fusion imaging (71.2%) and MRI-US fusion imaging (62.1%) were clearly favored. Compared with participants in community practices and from central-west region of China, those in academic practices and from east region of China were more likely to report utilization of mpMRI [odds ratio (OR) =2.08 and OR =0.19] and mpUS (OR =0.04 and OR =0.33) and recommendation of MRI targeted biopsy (OR =1.50 and OR =0.15) (P<0.05 in all). Conclusions:The majority of specialists perceived that mpMRI was routinely used, while only a small proportion of them reported the use of mpUS in clinical practice. Participants in academic practices and from east region of China had greater self-reported use of mpMRI and mpUS and recommendation of MRI targeted biopsy.

OBJECTIVE:To investigate the diagnostic performance of standard ultrasound (US) using a US-adapted Bosnian classification for characterizing cystic renal masses (CRMs) compared with computed tomography/magnetic resonance imaging (CT/MRI) as the current standard. METHODS:From July 2016 to June 2022, pathology-proven CRMs and CRMs with ≥3 y of follow-up from six centers were reviewed. Four readers with varying levels of expertise in US categorized CRMs using a US-based Bosnian classification, followed by a consensus reading by two high-level readers. For CRMs with concurrent CT/MRI, the CT/MRI Bosniak classification was performed again by a blinded radiologist. With a cut-off category of ≥III as malignancy, diagnostic performance was compared using receiver operating characteristic curve analysis. Inter-modality agreement and inter-observer variability were statistically evaluated. RESULTS:A total of 603 CRMs graded to US Bosniak I, II, IIF, III and IV were analyzed, including 239 pathology-proven lesions and 364 lesions with adequate follow-up. The area under curve was 0.78 for US and 0.82 for CT/MRI, with a sensitivity of 77% versus 86% and a specificity of 79% versus 78%, respectively, showing no significant differences (p = 0.17). US and CT/MRI classifications matched in 68% (substantial agreement, kappa [κ] = 0.75), with US leading to higher scores in 19.5%. Comparison with reader consensus was substantial (highest κ = 0.77) for low-level readers and excellent (highest κ = 0.89) for high-level readers. Inter-observer variability showed substantial agreement (κ = 0.66) in low-level readers and excellent agreement (κ = 0.88) in high-level readers. CONCLUSION:US-based Bosniak classification is reproducible and effective for identifying malignancy among CRMs, offering a lower-cost alternative to contrast-enhanced modalities, which is particularly important in resource-limited care settings.

The design of ultrasound (US)-responsive nanocarriers (URNs) guided by their physicochemical characteristics represents a pivotal strategy for advancing cancer therapy. By exploiting the intrinsic physicochemical properties of diverse nanocarriers, including liposomes, polymers, nanobubbles (NBs)/nanodroplets (NDs), inorganic composites, and metal-organic frameworks (MOFs), URNs achieve precise spatiotemporal control over drug delivery, enhanced tumor penetration, and synergistic therapeutic outcomes under US stimulation. Leveraging US-induced mechanical and thermal effects, URNs exhibit expanding multimodal capabilities, encompassing gene delivery, chemo-sonodynamic therapy, immunomodulation, and gas-mediated reprogramming of the tumor microenvironment (TME). Despite significant preclinical progress, the clinical translation of URNs requires addressing key challenges: (1) inconsistent pharmacokinetics and long-term biosafety profiles; (2) insufficient targeting efficiency due to tumor heterogeneity; (3) a lack of standardized US parameter protocols to balance cavitation and thermal effects; and (4) challenges in scalable manufacturing and quality control. This review systematically evaluates the structure-property-function correlations in URN design, analyzes the physicochemical determinants of acoustic responsiveness alongside current limitations, and proposes a roadmap that integrates computational modeling, stimuli-responsive materials, and artificial intelligence (AI)-assisted parameter optimization to advance next-generation URNs, ultimately outlining future directions for personalized oncology and clinical translation.

Castration-resistant prostate cancer (CRPC) is an intractable disease, but approaches for eradicating primary tumors and inhibiting metastasis are limited. Considering that lipid metabolism plays key roles in ferroptosis and tumor progression and treatment resistance, here we developed a biomimetic nanovesicle (FiFe@RBM) encapsulating fatty acid synthetase inhibitors and iron oxide nanoparticles for synergistic therapy of CRPC and inhibiting the metastasis. FiFe@RBM with superior magnetic properties efficiently delivered drugs into the CRPC cancer cells, where it can release Fe ions to efficiently induce reactive oxygen species and mitochondrial dysfunction and inhibit the AKT-mTOR pathway, which synergistically causes apoptosis and enhances ferroptosis by rewired lipid metabolism through increasing polyunsaturated fatty acids (PUFAs), PUFA-enriched phosphatidylcholine (PUFA-PC), PUFA-enriched phosphatidylethanolamine (PUFA-PE), etc. By intravenous injection, the high accumulation of FiFe@RBM in PC-3 tumors enabled precision T1/T2-weighted magnetic resonance imaging-guided effective eradication of human CRPC PC-3 tumors by synergistic magnetic hyperthermia therapy (MHT) and ferroptosis, which further inhibited liver metastasis by the activated and recruited high rates of natural killer cells in the nude mice model. This work presents an effective nanovesicle strategy for reprogramming lipid metabolism to enhance ferroptosis in synergy with MHT for effectively treating refractory cancers.

Objectives To develop and validate a predictive model based on clinical features and multiparametric magnetic resonance imaging (mpMRI) to reduce unnecessary systematic biopsies (SBs) in biopsy-naïve patients with suspected prostate cancer (PCa). Methods A total of 274 patients who underwent combined cognitive MRI-targeted biopsy (MRTB) with SB were retrospectively enrolled and temporally split into development ( n = 201) and validation ( n = 73) cohorts. Multivariable logistic regression analyses were used to determine independent predictors of clinically significant PCa (csPCa) on cognitive MRTB, and the clinical, MRI, and combined models were established respectively. Area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analyses were assessed. Results Prostate imaging data and reporting system (PI-RADS) score, index lesion (IL) on the peripheral zone, age, and prostate-specific antigen density (PSAD) were independent predictors and included in the combined model. The combined model achieved the best discrimination (AUC 0.88) as compared to both the MRI model incorporated by PI-RADS score, IL level, and zone (AUC 0.86) and the clinical model incorporated by age and PSAD (AUC 0.70). The combined model also showed good calibration and enabled great net benefit. Applying the combined model as a reference for performing MRTB alone with a cutoff of 60% would reduce 43.8% of additional SB, while missing 2.9% csPCa. Conclusions The combined model based on clinical and mpMRI findings improved csPCa prediction and might be useful in making a decision about which patient could safely avoid unnecessary SB in addition to MRTB in biopsy-naïve patients. Critical relevance statement The combined model based on clinical and mpMRI findings improved csPCa prediction and might be useful in making a decision about which patient could safely avoid unnecessary SB in addition to MRTB in biopsy-naïve patients. Key points • Age, PSAD, PI-RADS score, and peripheral index lesion were independent predictors of csPCa. • Risk models were used to predict the probability of detecting csPCa on cognitive MRTB. • The combined model might reduce 43.8% of unnecessary SBs, while missing 2.9% csPCa. Graphical Abstract

Background: Capsule-preserving hydrodilatation is a common treatment for adhesive capsulitis (AC), and ultrasound (US) has recently become the most popular adjuvant tool for image-guided glenohumeral joint injection. However, traditional US is hardly adequate to assess extracapsular fluid leakage, which may decide the treatment outcomes. In this study, we explored the value of contrast-enhanced ultrasound (CEUS) guided capsule-preserving hydrodilatation with steroids and ultrasonic contrast agents for treatment of AC. Methods: A total of 40 consecutive patients with AC were prospectively enrolled and received CEUS-guided capsule-preserving hydrodilatation. The number of injection attempts, injection volume, and fluid leakage were recorded, and the correlations with clinical features were analyzed by Pearson or Spearman correlation coefficients. Outcome measures including visual analog scale (VAS) score, passive range of motion (ROM), and shoulder pain and disability index (SPADI) score were evaluated at baseline and 4 weeks after treatment. Comparisons between patients with good and poor clinical outcomes were performed with independent t-test, Mann-Whitney U test, and chi-square test. Logistic regression was used to identify predictors of good clinical outcomes. A P value <0.05 defined significance. Results: Access to the glenohumeral joint was successful in 87.5% patients on the first attempt. The infused fluid volume was 21.0 +/- 3.40 mL. Longer symptom duration (r=-0.676, P<0.001), greater SPADI (r=-0.148, P=0.007), and decreased ROM in abduction (r=0.38, P=0.016) were associated with a decreased volume of infused fluid. CEUS detected massive fluid leakage in 5 (12.5%) patients, with 4 capsule ruptures confirmed by magnetic resonance imaging (MRI). Longer symptom duration (r=0.485, P=0.001), decreased ROM in the direction of abduction (r=-0.33, P=0.037), and external rotation (r=-0.34, P=0.032) were correlated with an increased incidence of massive fluid leakage. Moreover, patients with good outcomes had significantly shorter symptom duration (5.7 +/- 2.09 vs . 11.2 +/- 3.89 months, P=0.002) and greater initial VAS score (6.9 +/- 1.04 vs . 6.3 +/- 0.50, P=0.022) than those with poor outcomes. Absence of massive fluid leakage was an independent predictor of clinical good outcomes at 4 weeks after treatment [odd ratio (OR) =0.05, 95% confidential interval (CI): 0.003-0.882, P=0.041]. Conclusions: CEUS-guided capsule-preserving hydrodilatation allows real-time visualization of capsule dilatation, accurate detection of extracapsular fluid leakage, and identification of risks for capsule rupture. It provides an effective treatment for AC, and is useful to predict patients' clinical outcomes.

Microwave thermotherapy (MT) is a clinical local tumor ablation modality, but its applications are limited by its therapeutic efficacy and safety. Therefore, developing sensitizers to optimize the outcomes of MT is in demand in clinical practice. Herein, we engineered a special nanoframework (i.e., FdMI) based on a fucoidan-decorated zirconium metal-organic framework incorporating manganese ions and liquid physisorption for microwave tumor ablation. The monodisperse nanoframework exhibited both microwave thermal effects and microwave dynamic effects, which could effectively kill cancer cells by efficient intracellular drug delivery. Through fucoidan-mediated targeting of P-selectin in the tumor microenvironment (TME), the FdMI effectively accumulated in tumor regions, leading to significant eradication of orthotropic triple-negative breast cancer (TNBC) and aggressive Hepa1-6 liver tumors by the synergistic effects of microwave thermotherapy/dynamic therapy (MT/MDT). The eradication of primary tumors could activate systemic immune responses, which effectively inhibited distant TNBC tumors and lung metastasis of Hepa1-6 liver tumors, respectively. This work not only engineered nanoparticle sensitizers for tumor-targeted synergistic MT/MDT but also demonstrated that nanocarrier-based microwave tumor ablation could stimulate antitumor immunity to effectively inhibit distant and metastatic tumors, demonstrating the high potential for effectively managing advanced malignant tumors.

Background To evaluate the safety and efficacy of US-guided microwave ablation in patients with thyroid nodules at Zuckerkandl tubercle. Methods 103 consecutive patients with thyroid nodules at Zuckerkandl tubercle (ZTTN) were enrolled in this study from November 2017 to August 2021. Prior to the surgery or US-guided microwave ablation (MWA), preoperative ultrasound visualization of the recurrent laryngeal nerve (RLN) and ZTTN was performed, the size and the position relationship between them were observed. Patients were followed up at 1, 3, 6, and 12 months after MWA and the volume reduction rates (VRR) of the thyroid nodules were analyzed. Results All patients successfully had the RLN and ZTTN detected using ultrasound before surgery or ablation with a detection rate of 100%. For the 103 patients, the majority of ZTTN grades were categorized as grade 2, with the distance from the farthest outside of ZTTN to the outer edge of thyroid ranging between 6.0 and 10.0 mm. The position relationship between ZTTN and RLN was predominantly type A in 98 cases, with type D observed in 5 cases. After MWA, the median nodule volume had significantly decreased from 4.61 (2.34, 8.70) ml to 0.42 (0.15, 1.41) ml and the VRR achieved 84.36 ± 13.87% at 12 months. No nodules regrew throughout the 12-month follow-up period. Of the 11 patients experienced hoarseness due to RLN entrapment before ablation, 7 recovered immediately after separation of the RLN and ZTTN during MWA, 2 recovered after one week, and the other 2 recovered after two months. Conclusions The RLN is closely related to ZTTN and mainly located at the back of ZTTN. The RLN can be separated from ZTTN by hydrodissection during MWA. US-guided MWA is a safe and effective treatment for ZTTN.

Lip and oral cavity cancer is a severe and growing problem, ranked 16th for both incidence and mortality worldwide. These malignancies are mainly treated with surgery, which can cause a wide range of sequelae. Despite ultrasound-guided microwave ablation (MWA) being widely used, there is no report concerning its application in lip cancer. This study presents a case of ultrasound-guided MWA in a 97-year-old man with squamous cell carcinoma (SCC) and lymph node metastases under the lower lip. The patient was unsuitable for surgery due to his older age. At the most recent 1-year follow-up after treatment, the patient remained in good condition with no symptoms of dysphagia or slurred speech, and the cosmetic results were excellent. Based on clinical evaluation and radiographic imaging, there was no evidence of metastasis or recurrence. Ultrasound-guided MWA could be a promising option for the management of lip cancer.

Glioblastoma is the most common type of brain tumor. Due to the presence of the blood-brain barrier, the effects of chemotherapy have been unsatisfactory. The combination of focused ultrasound and microbubbles to reversibly open the blood-brain barrier is now considered a key factor in improving treatment outcomes of glioblastoma. In this study, we developed bionic drug delivery microbubbles, which in combination with focused ultrasound had an obvious inhibitory effect on glioblastoma. We extracted the brain microvascular cell membranes, combined them with lipid components, and loaded them with superparamagnetic iron oxide and doxorubicin to prepare biomimetic drug delivery microbubbles (FeDOX@cellMBs). We demonstrated that FeDOX@cellMBs retained the intrinsic properties of loading, such as magnetic properties and drug toxicity, both in vitro and in vivo. FeDOX@cellMBs exhibited good tumor targeting and uptake under the combined action of magnetic and focused ultrasound. Importantly, the FeDOX@cellMBs demonstrated excellent internal stability and effectively inhibited tumor growth in orthotopic glioblastoma mice. Finally, organ H&E staining confirmed that FeDOX@cellMBs were safe for use. In conclusion, FeDOX@cellMBs successfully penetrated the blood-brain barrier and effectively inhibited glioblastoma growth under the combined effects of focused ultrasound and magnetic stimulation. These results provide a new approach for the treatment of glioblastoma, with implications for future clinical translation.

Expression of Concern for 'Low-intensity focused ultrasound (LIFU)-activated nanodroplets as a theranostic agent for noninvasive cancer molecular imaging and drug delivery' by Jianxin Liu et al., Biomater. Sci., 2018, 6, 2838-2849, https://doi.org/10.1039/C8BM00726H.