Afterglow/Photothermal Bifunctional Polymeric Nanoparticles for Precise Postbreast-Conserving Surgery Adjuvant Therapy and Early Recurrence Theranostic.

Adjuvant whole-breast radiotherapy is essential for breast cancer patients who adopted breast-conserving surgery (BCS) to reduce the risk of local recurrences, which however suffer from large-area and highly destructive ionizing radiation-induced adverse events. To tackle this issue, an afterglow/photothermal bifunctional polymeric nanoparticle (APPN) is developed that utilizes nonionizing light for precise afterglow imaging-guided post-BCS adjuvant second near-infrared (NIR-II) photothermal therapy. APPN consists of a tumor cell targeting afterglow agent, which is doped with a NIR dye as an afterglow initiator and a NIR-II light-absorbing semiconducting polymer as a photothermal transducer. Such a design realizes precise afterglow imaging-guided NIR-II photothermal ablation of minimal residual breast tumor foci after BCS, thus achieving complete inhibition of local recurrences. Moreover, APPN enables early diagnosis and treatment of local recurrence after BCS. This study thus provides a nonionizing modality for precision post-BCS adjuvant therapy and early recurrence theranostic.

Simultaneous glutamine metabolism and PD-L1 inhibition to enhance suppression of triple-negative breast cancer.

Blockade of programmed cell death 1 ligand (PD-L1) has been used to treat triple-negative breast cancer (TNBC), and various strategies are under investigation to improve the treatment response rate. Inhibition of glutamine metabolism can reduce the massive consumption of glutamine by tumor cells and meet the demand for glutamine by lymphocytes in tumors, thereby improving the anti-tumor effect on the PD-L1 blockade therapy. Here, molybdenum disulfide (MoS2) was employed to simultaneously deliver anti-PDL1 antibody (aPDL1) and V9302 to boost the anti-tumor immune response in TNBC cells. The characterization results show that MoS2 has a dispersed lamellar structure with a size of about 181 nm and a size of 232 nm after poly (L-lysine) (PLL) modification, with high stability and biocompatibility. The loading capacity of aPDL1 and V9302 are 3.84% and 24.76%, respectively. V9302 loaded MoS2 (MoS2-V9302) can effectively kill 4T1 cells and significantly reduce glutamine uptake of tumor cells. It slightly increases CD8+ cells in the tumor and promotes CD8+ cells from the tumor edge into the tumor core. In vivo studies demonstrate that the combination of aPDL1 and V9302 (MoS2-aPDL1-V9302) can strongly inhibit the growth of TNBC 4T1 tumors. Interestingly, after the treatment of MoS2-aPDL1-V9302, glutamine levels in tumor interstitial fluid increased. Subsequently, subtypes of cytotoxic T cells (CD8+) in the tumors were analyzed according to two markers of T cell activation, CD69, and CD25, and the results reveal a marked increase in the proportion of activated T cells. The levels of cytokines in the corresponding tumor interstitial fluid are also significantly increased. Additionally, during the treatment, the body weights of the mice remain stable, the main indicators of liver and kidney function in the blood do not increase significantly, and there are no obvious lesions in the main organs, indicating low systemic toxicity. In conclusion, our study provides new insights into glutamine metabolism in the tumor microenvironment affects immune checkpoint blockade therapy in TNBC, and highlights the potential clinical implications of combining glutamine metabolism inhibition with immune checkpoint blockade in the treatment of TNBC.

Dye-loaded mesoporous polydopamine nanoparticles for multimodal tumor theranostics with enhanced immunogenic cell death.

BACKGROUND: Tumor phototherapy especially photodynamic therapy (PDT) or photothermal therapy (PTT), has been considered as an attractive strategy to elicit significant immunogenic cell death (ICD) at an optimal tumor retention of PDT/PTT agents. Heptamethine cyanine dye (IR-780), a promising PDT/PTT agent, which can be used for near-infrared (NIR) fluorescence/photoacoustic (PA) imaging guided tumor phototherapy, however, the strong hydrophobicity, short circulation time, and potential toxicity in vivo hinder its biomedical applications. To address this challenge, we developed mesoporous polydopamine nanoparticles (MPDA) with excellent biocompatibility, PTT efficacy, and PA imaging ability, facilitating an efficient loading and protection of hydrophobic IR-780. RESULTS: The IR-780 loaded MPDA (IR-780@MPDA) exhibited high loading capacity of IR-780 (49.7 wt%), good physiological solubility and stability, and reduced toxicity. In vivo NIR fluorescence and PA imaging revealed high tumor accumulation of IR-780@MPDA. Furthermore, the combined PDT/PTT of IR-780@MPDA could induce ICD, triggered immunotherapeutic response to breast tumor by the activation of cytotoxic T cells, resulting in significant suppression of tumor growth in vivo. CONCLUSION: This study demonstrated that the as-developed compact and biocompatible platform could induce combined PDT/PTT and accelerate immune activation via excellent tumor accumulation ability, offering multimodal tumor theranostics with negligible systemic toxicity.

Chlorin e6-Biotin Conjugates for Tumor-Targeting Photodynamic Therapy.

To improve the tumor-targeting efficacy of photodynamic therapy, biotin was conjugated with chlorin e6 to develop a new tumor-targeting photosensitizer, Ce6-biotin. The Ce6-biotin had good water solubility and low aggregation. The singlet-oxygen generation rate of Ce6-biotin was slightly increased compared to Ce6. Flow cytometry and confocal laser scanning microscopy results confirmed Ce6-biotin had higher binding affinity toward biotin-receptor-positive HeLa human cervical carcinoma cells than its precursor, Ce6. Due to the BR-targeting ability of Ce6-biotin, it exhibited stronger cytotoxicity to HeLa cells upon laser irradiation. The IC50 against HeLa cells of Ce6-biotin and Ce6 were 1.28 µM and 2.31 µM, respectively. Furthermore, both Ce6-biotin and Ce6 showed minimal dark toxicity. The selectively enhanced therapeutic efficacy and low dark toxicity suggest that Ce6-biotin is a promising PS for BR-positive-tumor-targeting photodynamic therapy.

Deformable Hollow Periodic Mesoporous Organosilica Nanocapsules for Significantly Improved Cellular Uptake.

Mesoporous solids have been widely used in various biomedical areas such as drug delivery and tumor therapy. Although deformability has been recognized as a prime important characteristic influencing cellular uptake, the synthesis of deformable mesoporous solids is still a great challenge. Herein, deformable thioether-, benzene-, and ethane-bridged hollow periodic mesoporous organosilica (HPMO) nanocapsules have successfully been synthesized for the first time by a preferential etching approach. The prepared HPMO nanocapsules possess uniform diameters (240-310 nm), high surface areas (up to 878 m2·g-1), well-defined mesopores (2.6-3.2 nm), and large pore volumes (0.33-0.75 m3·g-1). Most importantly, the HPMO nanocapsules simultaneously have large hollow cavities (164-270 nm), thin shell thicknesses (20-38 nm), and abundant organic moiety in the shells, which endow a lower Young's modulus (EY) of 3.95 MPa than that of solid PMO nanoparticles (251 MPa). The HPMOs with low EY are intrinsically flexible and deformable in the solution, which has been well-characterized by liquid cell electron microscopy. More interestingly, it is found that the deformable HPMOs can easily enter into human breast cancer MCF-7 cells via a spherical-to-oval morphology change, resulting in a 26-fold enhancement in cellular uptake (43.1% cells internalized with nanocapsules versus 1.65% cells with solid counterparts). The deformable HPMO nanocapsules were further loaded with anticancer drug doxorubicin (DOX), which shows high killing effects for MCF-7 cells, demonstrating the promise for biomedical applications.

A Facile Multi-interface Transformation Approach to Monodisperse Multiple-Shelled Periodic Mesoporous Organosilica Hollow Spheres.

The synthesis of well-defined and complex hollow structures via a simple method is still a major challenge. In this work, a facile and controllable "multi-interface transformation" approach for preparation of monodisperse multi-shelled periodic mesoporous organosilica (PMO) hollow spheres has been established by a one-step hydrothermal treatment of successively grown organosilica particles. The multi-shelled PMO hollow spheres have inorganic-organic hybrid frameworks, controllable number (1-4) of shells, high surface area (∼805 m(2)/g), accessible ordered mesochannels (∼3.2 nm), large pore volume (1.0 cm(3)/g), and uniform and tunable diameter (300-550 nm), chamber size (4-54 nm), and shell thickness (10-30 nm). In addition, various organic groups (alkyl, aromatic, and heteroelement fragments) are successfully incorporated into the multi-shelled PMO hollow spheres by successively adding different bridged organosilica precursors. Notably, the distribution of different kinds of organic groups in the multi-shelled PMO hollow spheres can be precisely controlled, showing great potential for future applications. We propose that the formation of the multi-shelled PMO hollow structures is ascribed to the creation of multiple highly cross-linked organosilica interfaces, providing a new and interesting fundamental principle for PMO materials. Due to their unique structure and frameworks, triple-shelled ethane-bridged PMO hollow spheres were successfully loaded with an anti-cancer drug doxorubicin and perfluoropentane gas, which present excellent effects in the killing of cancer cells and ultrasound imaging. It is expected that the multi-interface transformation strategy provides a simple, controllable, versatile, and template-free method for preparation of various multifunctional PMOs for different applications.

Reversibly extracellular pH controlled cellular uptake and photothermal therapy by PEGylated mixed-charge gold nanostars.

Shielding nanoparticles from nonspecific interactions with normal cells/tissues before they reach and after they leave tumors is crucial for the selective delivery of NPs into tumor cells. By utilizing the reversible protonation of weak electrolytic groups to pH changes, long-chain amine/carboxyl-terminated polyethylene glycol (PEG) decorated gold nanostars (GNSs) are designed, exhibiting reversible, significant, and sensitive response in cell affinity and therapeutic efficacy to the extracellular pH (pHe) gradient between normal tissues and tumors. This smart nanosystem shows good dispersity and unimpaired photothermal efficacy in complex bioenvironment at pH 6.4 and 7.4 even when their surface charge is neutral. One PEGylated mixed-charge GNSs with certain surface composition, GNS-N/C 4, exhibits high cell affinity and therapeutic efficacy at pH 6.4, and low affinity and almost "zero" damage to cells at pH 7.4. Remarkably, this significant and sensitive response in cell affinity and therapeutic efficacy is reversible as local pH alternated. In vivo, GNS-N/C 4 shows higher accumulation in tumors and improved photothermal therapeutic efficacy than pH-insensitive GNSs. This newly developed smart nanosystem, whose cell affinity reversibly transforms in response to pHe gradient with unimpaired biostability, provides a novel effective means of tumor-selective therapy.

Salvianolic acid A shows selective cytotoxicity against multidrug-resistant MCF-7 breast cancer cells.

Multidrug resistance (MDR) is a major cause for incurable breast cancer. Salvianolic acid A (SAA), the hydrophilic polyphenolic derivative of Salvia miltiorrhiza Bunge (Danshen/Red Sage), was examined for cytotoxicities to MDR MCF-7 human breast cancer cells and their parental counterparts. We have shown that SAA inhibited proliferation, caused cell cycle arrest at the S phase, and induced apoptosis dose dependently to the two kinds of cancer cells. However, the resistant cells were significantly susceptible to the inhibition of SAA compared with the parental cells. SAA increased the level of reactive oxygen species (ROS) by 6.2-fold in the resistant cells, whereas the level of SAA-induced ROS changed only by 1.6-fold in their parental counterparts. Thus, the data showed that the selective cytotoxicity resulted from the hypersensitivity of the resistant cells to the strongly elevated ROS by SAA. In addition, SAA-triggered apoptosis was associated with increased caspase-3 activity, disrupted mitochondrial membrane potential, downregulated Bcl-2 expression, and upregulated Bax expression in the resistant cells. Moreover, SAA downregulated the level of P-glycoprotein, which was overexpressed in the resistant cells. This indicated that SAA modulated MDR. Furthermore, SAA showed higher antitumor activity than did doxorubicin in xenografts established from the resistant cells. The present work raised a possibility that SAA might be considered a potential choice to overcome MDR for the selective susceptibility of the resistant breast cancer cells to SAA treatment.

A rapid and convenient method for detecting a broad spectrum of malignant cells from malignant pleuroperitoneal effusion of patients using a multifunctional NIR heptamethine dye.

Detection of malignant cells from malignant effusion is crucial to establish or adjust therapies of patients with cancer. The conventional qualitative detection in malignant pleuroperitoneal effusion is cytological analysis, which is time-consuming and complicated. Therefore, a faster and more convenient detection strategy is urgently needed. In this study, we report a rapid method to detect malignant cells from malignant pleuroperitoneal effusion (hydrothorax and ascites) of patients using IR-808, a tumor-targeted near-infrared (NIR) fluorescent heptamethine dye (tNRI dye), which exhibited superior labeling efficacy without specific conjugation to biomarkers. The targeted imaging performance toward malignant cells using IR-808 was confirmed by comparing with normal cells, and the fluorescence stability assay of IR-808 in malignant effusion was performed from 1 h to 48 h. In order to save time and dose, the incubation time and concentration were optimized to 10 min and 5 µM, which were used to detect malignant cells from 28 clinical samples of malignant pleuroperitoneal effusion. The results revealed that IR-808 could be internalized selectively by malignant cells of samples, and these malignant cells could be easily distinguished from normal cells under a fluorescence microscope. The positive rates between cytological analysis and the IR-808 staining method were 86% (24/28) and 79% (22/28), respectively. An excellent concordance level (Kappa = 0.752, P < 0.001) was observed between the two methods. Our results indicated that IR-808, a new NIR fluorescent heptamethine dye with unique optical imaging and tumor targeting properties, could provide a fast and simple way to detect a broad spectrum of malignant cells from malignant pleuroperitoneal effusion in patients.

In vivo volumetric photoacoustic molecular angiography and therapeutic monitoring with targeted plasmonic nanostars.

Photoacoustic (PA) imaging promises deeper tissue penetration while maintaining rich optical contrast as compared to other high resolution optical imaging techniques. In this report, a near-infrared pulse laser serves as the excitation source, and 128 ultrasonic transducers are spirally distributed on a hemispherical surface to receive PA signals for three-dimensional (3D) image reconstruction. With these attributes, the unique modality produces an isotropic and homogeneous spatial resolution (∼200 µm) with penetration depth of centimeters. Cyclic Arg-Gly-Asp (RGD) peptides conjugated plasmonic gold nanostars (RGD-GNS) are designed to specifically target over-expressed integrin α(v)ß3 on tumor neovasculature, enabling highly sensitive angiography and photothermal therapy (PTT). After the administration of RGD-GNS, tumor angiogenesis is clearly imaged with enhanced contrast, and the growth of tumor is effectively inhibited by PTT after laser irradiation. This study suggest that the PA angiography with plasmonic RGD-GNS can be applied as a triple functional platform for tumor diagnosis, PTT, and treatment monitoring. This PA technique offers deeper imaging depth with homogeneous resolution over existing optical imaging techniques for early diagnosis of tumor angiogenesis as well as on-the-spot nanotherapeutic evaluation.

Double-layer hollow mesoporous silica nanoparticles for ultrasound-guided photodynamic treatment.

Cervical carcinoma persists as a major global public health burden. While conventional therapeutic modalities inevitably cause ablation of adjacent non-tumorous tissues, photodynamic therapy (PDT) offers a targeted cytotoxic strategy through a photosensitizing agent (PS). However, the hydrophobicity and lack of selective accumulation of promising PS compounds such as zinc(II) phthalocyanine (ZnPc) impedes their clinical translation as standalone agents. The present study sought to incorporate ZnPc within double-layer hollow mesoporous silica nanoparticles (DHMSN) as nanocarriers to enhance aqueous dispersibility and tumor specificity. Owing to their compartmentalized design, the hollow mesoporous silica nanoparticles (HMSN) demonstrated enhanced ultrasonic imaging contrast. Combined with the vaporization of the perfluorocarbon perfluoropentane (PFP), the HMSN-encapsulated ZnPc enabled real-time ultrasound monitoring of PDT treatment.In vivo, the innate thermal energy induced vaporization of the DHMSN-carried PFP to significantly amplify ultrasound signals from the tumor site. Results demonstrated biocompatibility, efficient PFP microbubble generation, and robust photocatalytic activity. Collectively, this investigation establishes ultrasound-guided PDT utilizing multi-layer HMSN as a targeted therapeutic strategy for cervical malignancies with mitigated toxicity.

Fe-doped Cu-based bimetallic metal-organic frameworks as nanoscale microwave sensitizers for enhancing microwave thermal and dynamic therapy for hepatocellular carcinoma.

Microwave ablation (MWA) is recognized as a novel treatment modality that can kill tumor cells by heating the ions and polar molecules in these cells through high-speed rotation and friction. However, the size and location of the tumor affect the effective ablation range of microwave hyperthermia, resulting in residual tumor tissue and a high recurrence rate. Due to their tunable porous structure and high specific surface area, metal-organic frameworks (MOFs) can serve as microwave sensitizers, promoting microwave energy conversion owing to ion collisions in the porous structure of the MOFs. Moreover, iron-based compounds are known to possess peroxidase-like catalytic activity. Therefore, Fe-doped Cu bimetallic MOFs (FCMs) were prepared through a hydrothermal process. These FCM nanoparticles not only increased the efficiency of microwave-thermal energy conversion as microwave sensitizers but also promoted the generation of reactive oxygen species (ROS) by consuming glutathione (GSH) and promoted the Fenton reaction to enhance microwave dynamic therapy (MDT). The in vitro and in vivo results showed that the combination of MWA and MDT treatment effectively destroyed tumor tissues via microwave irradiation without inducing significant side effects on normal tissues. This study provides a new approach for the combined application of MOFs and microwave ablation, demonstrating excellent potential for future applications.

Prediction of pathological complete response of breast cancer patients who received neoadjuvant chemotherapy with a nomogram based on clinicopathologic variables, ultrasound, and MRI.

OBJECTIVE: To establish a nomogram for predicting the pathologic complete response (pCR) in breast cancer (BC) patients after NAC by applying magnetic resonance imaging (MRI) and ultrasound (US). METHODS: A total of 607 LABC women who underwent NAC before surgery between January 2016 and June 2022 were retrospectively enrolled, and then were randomly divided into the training (n = 425) and test set (n = 182) with the ratio of 7:3. MRI and US variables were collected before and after NAC, as well as the clinicopathologic features. Univariate and multivariate logistic regression analyses were applied to confirm the potentially associated predictors of pCR. Finally, a nomogram was developed in the training set with its performance evaluated by the area under the receiver operating characteristics curve (ROC) and validated in the test set. RESULTS: Of the 607 patients, 108 (25.4%) achieved pCR. Hormone receptor negativity (odds ratio [OR], 0.3; P < .001), human epidermal growth factor receptor 2 positivity (OR, 2.7; P = .001), small tumour size at post-NAC US (OR, 1.0; P = .031), tumour size reduction ≥50% at MRI (OR, 9.8; P < .001), absence of enhancement in the tumour bed at post-NAC MRI (OR, 8.1; P = .003), and the increase of ADC value after NAC (OR, 0.3; P = .035) were all significantly associated with pCR. Incorporating the above variables, the nomogram showed a satisfactory performance with an AUC of 0.884. CONCLUSION: A nomogram including clinicopathologic variables and MRI and US characteristics shows preferable performance in predicting pCR. ADVANCES IN KNOWLEDGE: A nomogram incorporating MRI and US with clinicopathologic variables was developed to provide a brief and concise approach in predicting pCR to assist clinicians in making treatment decisions early.

Self-assembly of amphiphilic plasmonic micelle-like nanoparticles in selective solvents.

Amphiphilic plasmonic micelle-like nanoparticles (APMNs) composed of gold nanoparticles (AuNPs) and amphiphilic block copolymers (BCPs) structurally resemble polymer micelles with well-defined architectures and chemistry. The APMNs can be potentially considered as a prototype for modeling a higher-level self-assembly of micelles. The understanding of such secondary self-assembly is of particular importance for the bottom-up design of new hierarchical nanostructures. This article describes the self-assembly, modeling, and applications of APMN assemblies in selective solvents. In a mixture of water/tetrahydrofuran, APMNs assembled into various superstructures, including unimolecular micelles, clusters with controlled number of APMNs, and vesicles, depending on the lengths of polymer tethers and the sizes of AuNP cores. The delicate interplay of entropy and enthalpy contributions to the overall free energy associated with the assembly process, which is strongly dependent on the spherical architecture of APMNs, yields an assembly diagram that is different from the assembly of linear BCPs. Our experimental and computational studies suggested that the morphologies of assemblies were largely determined by the deformability of the effective nanoparticles (that is, nanoparticles together with tethered chains as a whole). The assemblies of APMNs resulted in strong absorption in near-infrared range due to the remarkable plasmonic coupling of Au cores, thus facilitating their biomedical applications in bioimaging and photothermal therapy of cancer.

Biodegradable gold nanovesicles with an ultrastrong plasmonic coupling effect for photoacoustic imaging and photothermal therapy.

The hierarchical assembly of gold nanoparticles (GNPs) allows the localized surface plasmon resonance peaks to be engineered to the near-infrared (NIR) region for enhanced photothermal therapy (PTT). Herein we report a novel theranostic platform based on biodegradable plasmonic gold nanovesicles for photoacoustic (PA) imaging and PTT. The disulfide bond at the terminus of a PEG-b-PCL block-copolymer graft enables dense packing of GNPs during the assembly process and induces ultrastrong plasmonic coupling between adjacent GNPs. The strong NIR absorption induced by plasmon coupling and very high photothermal conversion efficiency (η=37%) enable simultaneous thermal/PA imaging and enhanced PTT efficacy with improved clearance of the dissociated particles after the completion of PTT. The assembly of various nanocrystals with tailored optical, magnetic, and electronic properties into vesicle architectures opens new possibilities for the construction of multifunctional biodegradable platforms for biomedical applications.

Quantitative evaluation of Kaiser score in diagnosing breast dynamic contrast-enhanced magnetic resonance imaging for patients with high-grade background parenchymal enhancement.

Background: High-grade background parenchymal enhancement (BPE), including moderate and marked, poses a considerable challenge for the diagnosis of breast disease due to its tendency to increase the rate of false positives and false negatives. The purpose of our study was to explore whether the Kaiser score can be used for more accurate assessment of benign and malignant lesions in high-grade BPE compared with the Breast Imaging Reporting and Data System (BI-RADS). Methods: A retrospective review was conducted on consecutive breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) scans from 2 medical centers. Included were patients who underwent DCE-MRI demonstrating high-grade BPE and who had a pathology-confirmed diagnosis. Excluded were patients who had received neoadjuvant chemotherapy or who had undergone biopsy prior to MRI examination. Two physicians with more than 7 years of experience specializing in breast imaging diagnosis jointly reviewed breast magnetic resonance (MR) images. The Kaiser score was used to determine the sensitivity, specificity, and positive predictive value (PPV), and negative predictive value (NPV) of the BI-RADS from different BPE groups and different enhancement types. The performance of the Kaiser score and BI-RADS were compared according to diagnostic accuracy. Results: A total of 126 cases of high-grade BPE from 2 medical centers were included in this study. The Kaiser score had a higher specificity and PPV than did the BI-RADS (87.5% vs. 46.3%) as well as a higher PPV (94.3% vs. 79.8%). The value of diagnostic accuracy and 95% confidence interval (CI) for the Kaiser score (accuracy 0.928; 95% CI: 0.883-0.973) was larger than that for BI-RADS (accuracy 0.810; 95% CI: 0.741-0.879). Moreover, the Kaiser score had a significantly higher value of diagnostic accuracy for both mass and non-mass enhancement, especially mass lesions (Kaiser score: accuracy 0.947, 95% CI: 0.902-0.992; BI-RADS: accuracy 0.821, 95% CI: 0.782-0.860), with a P value of 0.006. Conclusions: The Kaiser score is a useful diagnostic tool for the evaluation of high-grade BPE lesions, with a higher specificity, PPV, and diagnostic accuracy as compared to the BI-RADS.

Metaplastic Carcinoma of the Breast: MRI Features with Clinical and Histopathologic Correlation.

RATIONALE AND OBJECTIVES: Metaplastic carcinoma of the breast (MCB) is a rare type of breast carcinoma, and there are only limited data about the MRI findings of MCB. This article aimed to review the MRI features of MCB and correlate the MRI findings with clinical and histopathologic characteristics. MATERIALS AND METHODS: A total of 23 patients were enrolled from a signal institution. The clinical data, histological diagnosis and MRI findings were retrospectively reviewed. RESULTS: The average age of the 23 patients was 51.6 years. Twenty-one (91.3%) patients presented with a palpable mass. Squamous cell carcinoma was the most common subtype (10/23, 43.5%). Axillary lymph node metastasis was detected in 4 (17.4%) patients. The immunohistochemical profile showed the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor-2 (Her-2) expression were negative in 87.0%, 95.7%, and 91.3% of the patients respectively. On MRI, most cases exhibited an irregular mass (18/23, 78.3%) with high signal intensity on T2-weighted images (22/23,95.7%), non-circumscribed margin (19/23, 82.6%), heterogeneous enhancement (13/23, 56.5%), Type III (12/23, 52.2%) time intensity curve, and diffusion restriction (20/23, 87.0%) on diffusion weighted images (DWI). CONCLUSION: MCB most commonly demonstrated definitely malignant MRI features, which may reflect the histopathologic characteristic of this rare and aggressive breast carcinoma.

Hollow-polydopamine-nanocarrier-based near-infrared-light/pH-responsive drug delivery system for diffuse alveolar hemorrhage treatment.

Introduction: Diffuse alveolar hemorrhage (DAH) is a serious complication caused by systemic lupus erythematosus (SLE). Tissue damage and changes in immune response are all associated with excessive free radical production. Therefore, removing excess reactive oxygen species are considered a feasible scheme for diffuse alveolar hemorrhage treatment. Cyclophosphamide is often used as the main therapeutic drug in clinics. However, CTX carries a high risk of dose-increasing toxicity, treatment intolerance, and high recurrence rate. The combination of therapeutic drugs and functional nanocarriers may provide an effective solution. PDA is rich in phenolic groups, which can remove the reactive oxygen species generated in inflammatory reactions, and can serve as excellent free radical scavengers. Methods: We developed a hollow polydopamine (HPDA) nanocarrier loaded with CTX by ionization to prepare the novel nanoplatform, CTX@HPDA, for DAH treatment. The monodisperse silica nanoparticles were acquired by reference to the typical Stober method. PDA was coated on the surface of SiO2 by oxidation self-polymerization method to obtain SiO2@PDA NPs. Then, HPDA NPs were obtained by HF etching. Then HPDA was loaded with CTX by ionization to prepare CTX@HPDA. Then we tested the photothermal effect, animal model therapeutics effect, and biosafety of CTX@HPDA. Results: Material tests showed that the CTX@ HPDA nanoplatform had a uniform diameter and could release CTX in acidic environments. The vitro experiments demonstrated that CTX@HPDA has good photothermal conversion ability and photothermal stability. Animal experiments demonstrated that the CTX@HPDA nanoplatform had good biocompatibility. The nanoplatform can dissociate in acidic SLE environment and trigger CTX release through photothermal conversion. Combining HPDA, which scavenges oxygen free radicals, and CTX, which has immunosuppressive effect, can treat pulmonary hemorrhage in SLE. Micro-CT can be used to continuously analyze DAH severity and lung changes in mice after treatment. The pulmonary exudation in the various treatment groups improved to varying degrees. Discussion: In this study, we report a photothermal/PH-triggered nanocarrier (CTX@HPDA) for the precise treatment of SLE-DAH. CTX@HPDA is a simple and efficient nanocarrier system for DAH therapy. This work provides valuable insights into SLE treatment.

Theranostic mesoporous platinum nanoplatform delivers halofuginone to remodel extracellular matrix of breast cancer without systematic toxicity.

The enriched collagens in the extracellular matrix (ECM) of breast cancer substantially impede drug delivery. Halofuginone (HF), a potent antifibrotic agent, was effective to deplete the collagens and remodel the ECM by inhibiting the TGFß pathway. However, the application of HF was hindered by its strong liver toxicity. Herein, mesoporous platinum (mPt) nanoparticles were constructed to load HF as theranostic nanoplatforms. mPt had a uniform spherical structure with a diameter of 79.83 ± 6.97 nm and an average pore diameter of 20 nm and exhibited good photothermal conversion efficiency of 62.4%. The obtained HF-loaded nanoplatform (PEG@mPt-HF) showed enhanced cytotoxicity through the combination of photothermal therapy and the anti-TGFß effect induced by HF. The animal imaging and histochemical assays confirmed the PEG@mPt-HF could efficiently deliver HF to tumors (monitored by CT) and remodel the ECM by TGFß pathway inhibition, which resulted in increased anti-cancer efficacy. Importantly, the liver toxicity observed in HF-treated mice was negligible in those treated by PEG@mPt-HF. Overall, this study designed a theranostic nanoplatform to remodel the ECM with remarkably reduced systematic toxicity and enhance the therapeutic efficacy through combination treatment.

Interpretable XGBoost-SHAP Model Predicts Nanoparticles Delivery Efficiency Based on Tumor Genomic Mutations and Nanoparticle Properties.

Understanding the complex interaction between nanoparticles (NPs) and tumors in vivo and how it dominates the delivery efficiency of NPs is critical for the translation of nanomedicine. Herein, we proposed an interpretable XGBoost-SHAP model by integrating the information on NPs physicochemical properties and tumor genomic profile to predict the delivery efficiency. The correlation coefficients were 0.66, 0.75, and 0.54 for the prediction of maximum delivery efficiency, delivery efficiency at 24 and 168 h postinjection for test sets. The analysis of the feature importance revealed that the tumor genomic mutations and their interaction with NPs properties played important roles in the delivery of NPs. The biological pathways of the NP-delivery-related genes were further explored through gene ontology enrichment analysis. Our work provides a pipeline to predict and explain the delivery efficiency of NPs to heterogeneous tumors and highlights the power of simultaneously using omics data and interpretable machine learning algorithms for discovering interactions between NPs and individual tumors, which is important for the development of personalized precision nanomedicine.