Endowing Pt(IV) with Perfluorocarbon Chains and Human Serum Albumin Encapsulation for Highly Effective Antitumor Chemoimmunotherapy.

Tumor metastases and reoccurrence are considered the leading causes of cancer-associated deaths. As an emerging therapeutic method, increasing research efforts have been devoted to immunogenic cell death (ICD)-inducing compounds to solve the challenge. The clinically approved chemotherapeutic Pt complexes are not or are only poorly able to trigger ICD. Herein, the axial functionalization of the Pt(II) complex cisplatin with perfluorocarbon chains into ICD-inducing Pt(IV) prodrugs is reported. Strikingly, while the Pt(II) complex as well as the perfluorocarbon ligands did not induce ICD, the Pt(IV) prodrug demonstrated unexpectantly the induction of ICD through accumulation in the endoplasmic reticulum and generation of reactive oxygen species in this organelle. To enhance the pharmacological properties, the compound was encapsulated with human serum albumin into nanoparticles. While selectively accumulating in the tumorous tissue, the nanoparticles demonstrated a strong tumor growth inhibitory effect against osteosarcoma inside a mouse model. In vivo tumor vaccine analysis also demonstrated the ability of Pt(IV) to be an ideal ICD inducer. Overall, this study reports on axially perfluorocarbon chain-modified Pt(IV) complexes for ICD induction and chemoimmunotherapy in osteosarcoma.

Nanomedomics.

Nanomaterials have attractive physicochemical properties. A variety of nanomaterials such as inorganic, lipid, polymers, and protein nanoparticles have been widely developed for nanomedicine via chemical conjugation or physical encapsulation of bioactive molecules. Superior to traditional drugs, nanomedicines offer high biocompatibility, good water solubility, long blood circulation times, and tumor-targeting properties. Capitalizing on this, several nanoformulations have already been clinically approved and many others are currently being studied in clinical trials. Despite their undoubtful success, the molecular mechanism of action of the vast majority of nanomedicines remains poorly understood. To tackle this limitation, herein, this review critically discusses the strategy of applying multiomics analysis to study the mechanism of action of nanomedicines, named nanomedomics, including advantages, applications, and future directions. A comprehensive understanding of the molecular mechanism could provide valuable insight and therefore foster the development and clinical translation of nanomedicines.

A Trisulfide Bond Containing Biodegradable Polymer Delivering Pt(IV) Prodrugs to Deplete Glutathione and Donate H2S to Boost Chemotherapy and Antitumor Immunity.

The clinical application of cisplatin (CisPt) is limited by its dose-dependent toxicity. To overcome this, we developed reduction-responsive nanoparticles (NP(3S)s) for the targeted delivery of a platinum(IV) (Pt(IV)) prodrug to improve efficacy and reduce the toxicity. NP(3S)s could release Pt(II) and hydrogen sulfide (H2S) upon encountering intracellular glutathione, leading to potent anticancer effects. Notably, NP(3S)s induced DNA damage and activated the STING pathway, which is a known promoter for T cell activation. Comparative RNA profiling revealed that NP(3S)s outperformed CisPt in enhancing T cell immunity, antitumor immunity, and oxidative stress pathways. In vivo experiments showed that NP(3S)s accumulated in tumors, promoting CD8+ T cell infiltration and boosting antitumor immunity. Furthermore, NP(3S)s exhibited robust in vivo anticancer efficacy while minimizing the CisPt-induced liver toxicity. Overall, the results indicate NP(3S)s hold great promise for clinical translation due to their low toxicity profile and potent anticancer activity.

Treatment of Acute Wound Infections by Degradable Polymer Nanoparticle with a Synergistic Photothermal and Chemodynamic Strategy.

Mild-heat photothermal antibacterial therapy avoids heat-induced damage to normal tissues but causes bacterial tolerance. The use of photothermal therapy in synergy with chemodynamic therapy is expected to address this issue. Herein, two pseudo-conjugated polymers PM123 with photothermal units and PFc with ferrocene (Fc) units are designed to co-assemble with DSPE-mPEG2000 into nanoparticle NPM123/Fc. NPM123/Fc under 1064 nm laser irradiation (NPM123/Fc+NIR-II) generates mild heat and additionally more toxic ∙OH from endogenous H2O2, displaying a strong synergistic photothermal and chemodynamic effect. NPM123/Fc+NIR-II gives >90% inhibition rates against MDR ESKAPE pathogens in vitro. Metabolomics analysis unveils that NPM123/Fc+NIR-II induces bacterial metabolic dysregulation including inhibited nucleic acid synthesis, disordered energy metabolism, enhanced oxidative stress, and elevated DNA damage. Further, NPM123/Fc+NIR-II possesses >90% bacteriostatic rates at infected wounds in mice, resulting in almost full recovery of infected wounds. Immunodetection and transcriptomics assays disclose that the therapeutic effect is mainly dependent on the inhibition of inflammatory reactions and the promotion of wound healing. What is more, thioketal bonds in NPM123/Fc are susceptible to ROS, making it degradable with highly favorable biosafety in vitro and in vivo. NPM123/Fc+NIR-II with a unique synergistic antibacterial strategy would be much less prone to select bacterial resistance and represent a promising antibiotics-alternative anti-infective measure.

Stimulus-Responsive Copper Complex Nanoparticles Induce Cuproptosis for Augmented Cancer Immunotherapy.

Cuproptosis, an emerging form of programmed cell death, has received tremendous attention in cancer therapy. However, the efficacy of cuproptosis remains limited by the poor delivery efficiency of copper ion carriers. Herein, copper complex nanoparticles (denoted as Cu(I) NP) are developed that can efficiently deliver copper complex into cancer cells to induce cuproptosis. Cu(I) NP demonstrate stimulus-responsive release of copper complexes, which results in mitochondrial dysfunction and promotes the aggregation of lipoylated dihydrolipoamide S-acetyltransferase (DLAT), leading to cuproptosis. Notably, Cu(I) NP not only induce cuproptosis, but also elicit robust immune responses to suppress tumor growth. Overall, this study provides a promising strategy for cuproptosis-based cancer therapy.

Cancer Nanobombs Delivering Artoxplatin with a Polyigniter Bearing Hydrophobic Ferrocene Units Upregulate PD-L1 Expression and Stimulate Stronger Anticancer Immunity.

Poor immunogenicity seriously hampers the broader implementation of antitumor immunotherapy. Enhanced immunogenicity capable of achieving greater antitumor immunity is urgently required. Here, a novel polymer that contains hydrophobic ferrocene (Fc) units and thioketal bonds in the main chain, which further delivered a prodrug of oxaliplatin and artesunate, i.e., Artoxplatin, to cancer cells is described. This polymer with Fc units in the nanoparticle can work as a polyigniter to spark the peroxide bonds in Artoxplatin and generate abundant reactive oxygen species (ROS) to kill cancers as nanobombig for cancer therapy. Moreover, ROS can trigger the breakdown of thioketal bonds in the polymer, resulting in the biodegradation of the polymer. Importantly, nanobombig can facilitate the maturation of dendritic cells and promote the activation of antitumor immunity, through the enhanced immunogenic cell death effect by ROS generated in situ. Furthermore, metabolomics analysis reveals a decrease in glutamine in nanobombig -treated cancer cells, resulting in the upregulation of programmed death ligand 1 (PD-L1). Consequently, it is further demonstrated enhanced tumor inhibitory effects when using nanobombig combined with anti-PD-L1 therapy. Overall, the nanosystem offers a rational design of an efficient chemo-immunotherapy regimen to promote antitumor immunity by improving tumor immunogenicity, addressing the key challenges cancer immunotherapy faced.

Localization of Cancer Cells for Subsequent Robust Photodynamic Therapy by ROS Responsive Polymeric Nanoparticles With Anti-Metastasis Complexes NAMI-A.

Photodynamic therapy (PDT), as a new type of light-mediated reactive oxygen species (ROS) cancer therapy, has the advantages of high therapeutic efficiency, non-resistance, and less trauma than traditional cancer therapy such as surgery, radiotherapy, and chemotherapy. However, oxygen-dependent PDT further exacerbates tumor metastasis. To this end, a strategy that circumvents tumor metastasis to improve the therapeutic efficacy of PDT is proposed. Herein, a near-infrared light-activated photosensitive polymer is synthesized and branched the anti-metastatic ruthenium complex NAMI-A on the side, which is further assembled to form nanoparticles (NP2) for breast cancer therapy. NP2 can kill tumor cells by generating ROS under 808 nm radiation (NP2 + L), reduce the expression of matrix metalloproteinases (MMP2/9) in cancer cells, decrease the invasive and migration capacity of cancer cells, and eliminate cancer cells. Further animal experiments show that NP2 + L can inhibit tumor growth and reduce liver and lung metastases. In addition, NP2 + L can activate the immune system in mice to avoid tumor recurrence. In conclusion, a PDT capable of both preventing tumor metastasis and precisely hitting the primary tumor to achieve effective treatment of highly metastatic cancers is developed.

Spatiotemporal single-cell transcriptomic profiling reveals inflammatory cell states in a mouse model of diffuse alveolar damage.

Diffuse alveolar damage (DAD) triggers neutrophilic inflammation in damaged tissues of the lung, but little is known about the distinct roles of tissue structural cells in modulating the recruitment of neutrophils to damaged areas. Here, by combining single-cell and spatial transcriptomics, and using quantitative assays, we systematically analyze inflammatory cell states in a mouse model of DAD-induced neutrophilic inflammation after aerosolized intratracheal inoculation with ricin toxin. We show that homeostatic resident fibroblasts switch to a hyper-inflammatory state, and the subsequent occurrence of a CXCL1-CXCR2 chemokine axis between activated fibroblasts (AFib) as the signal sender and neutrophils as the signal receiver triggers further neutrophil recruitment. We also identify an anatomically localized inflamed niche (characterized by a close-knit spatial intercellular contact between recruited neutrophils and AFib) in peribronchial regions that facilitate the pulmonary inflammation outbreak. Our findings identify an intricate interplay between hyper-inflammatory fibroblasts and neutrophils and provide an overarching profile of dynamically changing inflammatory microenvironments during DAD progression.

cGAS-STING Pathway Activation and Systemic Anti-Tumor Immunity Induction via Photodynamic Nanoparticles with Potent Toxic Platinum DNA Intercalator Against Uveal Melanoma.

The cGAS-STING pathway, as a vital innate immune signaling pathway, has attracted considerable attention in tumor immunotherapy research. However, STING agonists are generally incapable of targeting tumors, thus limiting their clinical applications. Here, a photodynamic polymer (P1) is designed to electrostatically couple with 56MESS-a cationic platinum (II) agent-to form NPPDT -56MESS. The accumulation of NPPDT -56MESS in the tumors increases the efficacy and decreases the systemic toxicity of the drugs. Moreover, NPPDT -56MESS generates reactive oxygen species (ROS) under the excitation with an 808 nm laser, which then results in the disintegration of NPPDT -56MESS. Indeed, the ROS and 56MESS act synergistically to damage DNA and mitochondria, leading to a surge of cytoplasmic double-stranded DNA (dsDNA). This way, the cGAS-STING pathway is activated to induce anti-tumor immune responses and ultimately enhance anti-cancer activity. Additionally, the administration of NPPDT -56MESS to mice induces an immune memory effect, thus improving the survival rate of mice. Collectively, these findings indicate that NPPDT -56MESS functions as a chemotherapeutic agent and cGAS-STING pathway agonist, representing a combination chemotherapy and immunotherapy strategy that provides novel modalities for the treatment of uveal melanoma.

Bioorthogonal Guided Activation of cGAS-STING by AIE Photosensitizer Nanoparticles for Targeted Tumor Therapy and Imaging.

Photodynamic therapy (PDT) and photothermal therapy (PTT) leverage reactive oxygen species (ROS) and control local hyperthermia by photosensitizer to perturb intracellular redox equilibrium, inducing DNA damage in both mitochondria and nucleus, activating the cGAS-STING pathway, ultimately eliciting antitumor immune responses. However, current photosensitizers are encumbered by limitations such as suboptimal tumor targeting, aggregation-caused quenching (ACQ), and restricted excitation and emission wavelengths. Here, this work designs novel nanoparticles based on aggregation-induced emission (AIE) photosensitizer (BODTPE) for targeted tumor therapy and near-infrared II fluorescence imaging (NIR-II FLI) with enhanced PDT/PTT effects. BODTPE is employed as a monomer, dibenzocyclooctyne (DBCO)-PEG2k -amine serving as an end-capping polymer, to synthesize a BODTPE-containing polymer (DBD). Further, through self-assembly, DBD and mPEG-DSPE2k combined to form nanoparticles (NP-DBD). Notably, the DBCO on the surface of NP-DBD can react with azide groups on cancer cells pretreated with Ac4 ManNAz through a copper-free click reaction. This innovative formulation led to targeted accumulation of NP-DBD within tumor sites, a phenomenon convincingly demonstrated in murine tumor models subjected to N-azidoacetylmannosamine-tetraacylated (Ac4 ManNAz) pretreatment. Significantly, NP-DBD exhibits a multifaceted effect encompassing PDT/PTT/NIR-II FLI upon 808 nm laser irradiation, thereby better activating the cGAS-STING pathway, culminating in a compelling tumor inhibition effect augmented by robust immune modulation.

Near-Infrared Fluorescent Probe for the In Situ Visualization of Oxidative Stress in the Brains of Neuroinflammatory and Schizophrenic Mice.

Schizophrenia is a common mental disorder with unclear mechanisms. Oxidative stress and neuroinflammation play important roles in the pathological process of schizophrenia. Superoxide anion (O2•-) is an important oxidative stress biomarker in vivo. However, due to the existence of the blood-brain barrier (BBB), few near-infrared (NIR) fluorescent probes have been used for the sensing and detection of O2•- in the brain. With this research, we developed the first near-infrared fluorescent probe (named CT-CF3) for noninvasive detection of endogenous O2•- in the brain of mice. Enabling fluorescence monitoring of the dynamic changes in O2•- flux due to the prolonged activation of microglia in neuroinflamed and schizophrenic (SZ) mice brains, thereby providing direct evidence for the relationship between oxidative stress, neuroinflammation, and schizophrenia. Furthermore, we confirmed the O2•- burst in the brains of first-episode schizophrenic mice and assessed the effect of two atypical antipsychotic drugs (risperidone and olanzapine) on redox homeostasis.

NIR-II Light Accelerated Prodrug Reduction of Pt(IV)-Incorporating Pseudo Semiconducting Polymers for Robust Degradation and Maximized Photothermal/Chemo-Immunotherapy.

Selective activation of Pt(IV) prodrugs within tumors is particularly attractive because of their low damage to normal tissues. However, current common activation via chemical/photoreduction of Pt(IV) prodrugs into Pt(II) counterparts is limited by undesirable spatial-temporal control over this reduction process and the ineffective tissue penetration depth of undesirable light. Here, a pseudo-conjugated-polymer is designed via Stille polymerization, resulting in PSP-Pt with a Pt(IV) prodrug of oxaliplatin (Oxa(IV)) in the polymer main chain that can be activated by NIR-II light. PSP-Pt can co-assemble with a commercially available lipid polymer, namely mPEG2k -DSPE, into NPPSP-Pt . Under 1064 nm light irradiation, NPPSP-Pt can be photoactivated to accelerate the Pt(IV) reduction to release oxaliplatin, thereby killing the cancer cells by photothermal effect and chemo-immunotherapy inside a mouse model with CT26 colon cancer. This work reports the application of NIR-II light for accelerating Pt(IV) reduction for cancer tumor therapy.

Reduction of Platinum(IV) Prodrug Hemoglobin Nanoparticles with Deeply Penetrating Ultrasound Radiation for Tumor-Targeted Therapeutically Enhanced Anticancer Therapy.

The development of PtIV prodrugs that are reduced into the therapeutically active PtII species within the tumor microenvironment has received much research interest. In order to provide spatial and temporal control over the treatment, there is a high demand for the development of compounds that could be selectively activated upon irradiation. Despite recent progress, the majority of PtIV complexes are excited with ultraviolet or blue light, limiting the use of such compounds to superficial application. To overcome this limitation, herein, the first example of PtIV prodrug nanoparticles that could be reduced with deeply penetrating ultrasound radiation is reported, enabling the treatment of deep-seated or large tumors. The nanoparticles were found to selectively accumulate inside a mouse colon carcinoma tumor upon intravenous injection and were able to eradicate the tumor upon exposure to ultrasound radiation.

Tetrahedral DNA Nanostructure with Interferon Stimulatory DNA Delivers Highly Potent Toxins and Activates the cGAS-STING Pathway for Robust Chemotherapy and Immunotherapy.

Tumor metastases and reoccurrences are considered the leading cause of cancer-associated deaths. While highly efficient treatments for the eradication of primary tumors have been developed, the treatment of secondary or metastatic tumors remains poorly accessible. Over the past years, compounds that intervene through the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway against tumor metastases have emerged with potential for clinical development. While interferon stimulatory DNAs have demonstrated activation of this pathway, these compounds are associated with poor bioavailability, poor stability, and poor cancer selectivity, hindering their use for therapeutic applications. Herein, the encapsulation of a highly potent chemotherapeutic platinum(II) complex and the incorporation of interferon stimulatory DNA strands for activation of the cGAS-STING pathway into multimodal tetrahedral DNA nanostructures (84bp-TDNISD/56MESS ) for combined chemotherapy and immunotherapy is reported. It is found that 84bp-TDNISD/56MESS can work as not only a drug delivery carrier for highly potent toxins, but also an immunostimulant agent that can activate the STING pathway for antitumor immune responses. In a mouse breast cancer model, the DNA nanostructure is found to nearly fully eradicate primary as well as secondary/metastatic tumors, hence demonstrating its potential clinical translational value.

Enhanced fluorescence/magnetic resonance dual imaging and gene therapy of liver cancer using cationized amylose nanoprobe.

Recently, various technologies for targeted gene release in cancer treatment have emerged. However, most of these strategies are facing the challenge of untraceable distribution and poor antitumour treatment effects. In this study, we constructed a gene delivery system that integrated a series of components to assemble multifunctional NPs, providing a promising theranostic nanoplatform for hepatocellular carcinoma (HCC) therapy. Cationized amylose (CA), superparamagnetic iron oxide (SPIO) nanoparticles (NPs), and tetraphenylethylene (TPE) were self-assembled to form nanospheres (CSP/TPE). The prepared NPs was modified with SP94 pepide through amidation reaction, and then survivin small interfering RNA (siRNA) were loaded into the NPs to form CSP/TPE@siRNA-SP94 NPs. Our results showed that the prepared NPs had good size distribution, high RNA condensation and transfection ability. CSP/TPE@siRNA-SP94 NPs exhibited excellent fluorescence and magnetic resonance (MR) imaging properties in vitro and in vivo. The prepared targeted NPs improved Huh-7 cellular uptake in vitro, and the biodistribution of CSP/TPE@siRNA-SP94 in vivo was observed through in/ex vivo fluorescence imaging system and MRI. As survivin siRNA effectively retained in tumour cells, CSP/TPE@siRNA-SP94 NPs considerably inhibited tumour growth in vivo. In addition, H&E staining results showed that all the prepared CSP-based NPs had good biocompatibilities, as few histological changes or tumour metastasis were observed in major organs of the mice in the treatment group. Therefore, we envisage that the prepared CSP/TPE@siRNA-SP94 NPs can represent a promising strategy for HCC diagnosis and treatment.

Controls of Hyperglycemia Improves Dysregulated Microbiota in Diabetic Mice.

BACKGROUND: Type 1 diabetes (T1DM) is a chronic autoimmune disease characterized by T-cell-mediated destruction of insulin-producing beta cells. Evidence shows that patients with T1DM and mice used in specific diabetic models both exhibit changes in their intestinal microbiota and dysregulated microbiota contributes to the pathogenesis of T1DM. Islet transplantation (Tx) is poised to play an important role in the treatment of T1DM. However, whether treatment of T1DM with islet Tx can rescue dysregulated microbiota remains unclear. METHODS: In this study, we induced diabetic C57BL/6 mice with streptozotocin. Then treatment with either insulin administration, or homogenic or allogenic islet Tx was performed to the diabetic mice. Total DNA was isolated from fecal pellets and high-throughput 16S rRNA sequencing was used to investigate intestinal microbiota composition. RESULTS: The overall microbial diversity was comparable between control (nonstreptozotocin treated) and diabetic mice. Our results showed the ratio of the Bacteroidetes: Firmicutes between nondiabetic and diabetic mice was significant different. Treatment with islet Tx or insulin partially corrects the dysregulated bacterial composition. At the genus level, Bacteroides, Odoribacter, and Alistipes were associated with the progression and treatment efficacy of the disease, which may be used as a biomarker to predict curative effect of treatment for patients with T1DM. CONCLUSIONS: Collectively, our results indicate that diabetic mice show changed microbiota composition and that treatment with insulin and islet Tx can partially correct the dysregulated microbiota.

Developing Push-Pull Hydroxylphenylpolyenylpyridinium Chromophores as Ratiometric Two-Photon Fluorescent Probes for Cellular and Intravital Imaging of Mitochondrial NQO1.

This work highlights the use of push-pull hydroxylphenylpolyenylpyridinium fluorophores coupled with trimethyl lock quinone to engineer the ratiometric two-photon probes for cellular and intravital imaging of mitochondrial NAD(P)H:quinone oxidoreductase 1 (NQO1), a critical antioxidant enzyme responsible for detoxifying quinones. As a typical representative, QBMP showed favorable binding with NQO1 with a Michaelis constant of 12.74 µM and exhibited a suite of superior properties, including rapid response (4 min), large Stokes shift (162 nm), ultralow detection limit (0.9 nM), favorable two-photon cross section for the released fluorophore (70.5 GM), and deep tissue penetration (225 µm) in fixed brain tissues. More importantly, this probe was successfully applied for distinguishing different NQO1-expressing cancer and normal cells, revealing decreased NQO1 activity in a cellular Parkinson's disease model, screening NQO1 inducers as neuroprotective agents, and imaging of NQO1 in live mouse brain.

Designing an ESIPT-based fluorescent probe for imaging of hydrogen peroxide during the ferroptosis process.

Hydrogen peroxide (H2O2), depending on its levels, plays a crucial role in either modulating various biological processes as a signal molecule, or mediating oxidative damage as a toxin. Therefore, monitoring intracellular H2O2 levels is pivotal for exploring its physiological and pathological roles. Using a modified 2-(2'-hydroxyphenyl) benzothiazole (HBT) as the fluorophore, and a pinacol phenylborate ester as the responsive group, herein we developed an excited-state intramolecular proton transfer (ESIPT)-based probe BTFMB. The probe exhibited turn-on fluorescence response, large Stokes shift (162 nm) and low detection limit (109 nM) toward H2O2, and was successfully applied for monitoring exogenous and endogenous production of H2O2, and identifying accumulation of H2O2 during the ferroptosis process.

Probing the structural, electronic, and adsorptive properties of Au16O2- clusters.

Great progress has been made in O2 adsorption on gold clusters. However, systematic investigations of O2 adsorption on [Formula: see text] clusters have not been reported. Here, we present a systematic study of the structural, electronic, and adsorptive properties of [Formula: see text] clusters by density functional theory (DFT) calculations coupled with stochastic kicking method. Global minimum searches for [Formula: see text] reveal that exohedral derivatives are more favored. Furthermore, the obtained ground-state structure exhibits significant stability, as judged by its larger adsorption energy (1.16 eV) and a larger HOMO-LUMO gap (0.57 eV). The simulated photoelectron spectra (PES) of [Formula: see text] isomers will be instructive to identify the structures in future experiments. There are three interesting discoveries in the present paper: (1) O2 undergoes chemical adsorption onto the parent [Formula: see text] clusters, but the amount of the adsorption energy is related to the parent [Formula: see text] clusters; (2) the process that O2 undergoes dissociative adsorption onto the parent [Formula: see text] clusters is exothermic; (3) [Formula: see text] isomers show smaller X-A energy gaps than those of parent [Formula: see text] clusters, reflecting that their geometric and electronic structures are distorted remarkably due to dissociative adsorption of O2.

Breast fibromatosis: Imaging and clinical findings.

Breast fibromatosis is a rare histologically benign tumor with local aggressive potential, and imaging and clinical findings of breast fibromatosis require attention. We retrospectively evaluated the images of 20 patients with histologically proven breast fibromatosis on mammography, magnetic resonance imaging (MRI), and ultrasonography. The lesions were assessed concerning the location, fascia involvement, imaging characteristics, and follow-up outcomes. Altogether, there were 22 lesions: 10 lesions involved the superficial fascia system including four lesions additionally involving the deep fascia and pectoralis major, and 12 lesions were inside the glandular parenchyma with two lesions originated from the prior surgery site. The detection rates of mammography, ultrasound, and MRI for breast fibromatosis were 33.3% (3/9), 90% (18/20), and 100% (3/3), respectively. We found that fascia involvement may be a characteristic of breast fibromatosis. The lesion located inside glandular parenchyma is prone to be underestimated, whereas combined MR with ultrasound is recommended for the diagnosis. The complete excision with negative margins is important for a good prognosis.