Tumor foci from four groups under fluorescence imaging system.

<p>Mice were sacrificed and scanned by fluorescent imaging system. Fluorescent tumor foci were observed on the parietal and visceral pleura as well as hilar and mediastinal lymph node. The number of fluorescent pleural tumor loci was significantly decreased in H-ES group (D) compared with that in NS group (A) and L-ES group (B). The number of fluorescent pleural tumor loci in Bevacizumab group (C) was similar with that in H-ES group (D). (E): The difference of the number of Tumor foci on mice from four groups. Columns: mean value of each group, bars: ±SD. ***P<0.001, **P<0.01, *P<0.05. ns: no significant difference.</p

CT scanning of MPE formation in four groups.

<p>CT images of four groups showed that bilateral pleural effusion was visible in the mice treated with NS (A) or L-ES (B),unilateral pleural effusion was observed in Bevacizumab group (C), and effusion was not obvious in H-ES group (D). The mean volume of pleural effusion was significantly decreased in the H-ES group compared with that in the NS group or L-ES group, but there is no significant difference between H-ES group and Bevacizumab group (E). MPE: malignant pleural effusion. Columns: mean value of each group, bars: ±SD. ***P<0.001, **P<0.01, *P<0.05. ns: no significant difference.</p

Immunohistochemistry staining of D2-40 for LMVD in the pleural tumors.

<p>Positive immunohistochemistry staining of D2-40 was shown as brown part in each figure. Positive endothelial cells stained by anti-D2-40 antibody were recognized as lymphatic vessels. Lymphatic micro vessel density (LMVD) was counted at Section×200. LMVD in H-ES group (D) was significantly decreased compared with NS group (A) or L-ES group (B) or Bevacizumab group(C). (E): The difference of LMVD on four groups. Columns: mean value of each group, bars: ±SD. ***P<0.001, **P<0.01, *P<0.05. ns: no significant difference.</p

Immunohistochemistry staining of CD31 for MVD in the pleural tumors.

<p>Positive immunohistochemistry staining of CD31 was shown as brown part in each figure. Micro-vessel density (MVD) was counted at Section×200. Well-formed capillaries were observed in the tumors from NS group (A) and L-ES group (B). Isolated micro-vessels were shown in Bevacizumab group (C) and H-ES group (D). MVD was significantly decreased in H-ES group compared with that in NS group or L-ES group, and there is no significant difference between Bevacizumab group and H-ES group (E).Columns: mean value of each group, bars: ±SD. ***P<0.001, ** P<0.01, *P<0.05. ns: no significant difference.</p

Histology of pleural tumors and cytology of MPE from the mice in NS group.

<p>(A) Hematoxylin-eosin staining of parietal pleura from MPE model (Section ×200) indicated that pleural tumors consisted of adenocarcinomatous cells. (B) Hematoxylin-eosin staining of tumor on the pleural surface from MPE model (Section ×200). (C) Wright’s-Giemsa stain of cells from pleural effusion of MPE model showed LLC cells with large nuclei and visible nucleoli (arrow). MPE: malignant pleural effusion.</p

JQ1-Loaded Polydopamine Nanoplatform Inhibits c‑MYC/Programmed Cell Death Ligand 1 to Enhance Photothermal Therapy for Triple-Negative Breast Cancer

Programmed cell death ligand 1 (PD-L1) blockade has achieved great success in cancer immunotherapy; however, the response of triple-negative breast cancer (TNBC) to PD-L1 antibodies is limited. To address this challenge, we use the bromodomain and extra-terminal inhibitor JQ1 to down-regulate the expression of PD-L1 and thus elicit the immune response to TNBC instead of using antibodies to block PD-L1. JQ1 also inhibits the growth of TNBC as a targeted therapeutic agent by inhibiting the BRD4-c-MYC axis. The polydopamine nanoparticles (PDMNs) are introduced as a biodegradable and adaptable platform to load JQ1 and induce photothermal therapy (PTT) as another synergistic therapeutic modality. Because the JQ1-loaded PDMNs (PDMN-JQ1) are self-degradable and release JQ1 continuously, this synergistic treatment can lead to remarkable activation of cytotoxic T lymphocytes and induce a strong immune-memory effect to protect mice from tumor re-challenge. Taken together, our study demonstrates a compact and simple nanoplatform for triple therapy, including targeted therapy, PTT, and immunotherapy, for TNBC treatment

Raman Reporter-Coupled Ag_core@Au_shell Nanostars for <i>in Vivo</i> Improved Surface Enhanced Raman Scattering Imaging and Near-infrared-Triggered Photothermal Therapy in Breast Cancers

Noble-metal nanomaterials were widely investigated as theranostic systems for surface enhanced Raman scattering (SERS) imaging, and also for photothermal therapy (PTT) of cancers. However, it was still a major challenge to explore multifunctional nanoprobes with high performance, high stability, and low toxicity. In this work, Raman reporter (DTTC)-coupled Ag_core@Au_shell nanostars (Ag@Au-DTTC) were synthesized and investigated for <i>in vivo</i> improved SERS imaging and near-infrared (NIR)-triggered PTT of breast cancers. By the two-step coupling of DTTC, the SERS signal was improved obviously, and the cytotoxicity of nanoparticles was also decreased by coating Au nanostars onto Ag nanoparticles. The as-prepared Ag@Au-DTTC nanostars showed high photostability and excellent photothermal performance, in which the photothermal conversion efficiency was up to 79.01% under the irradiation of an 808 nm laser. The <i>in vitro</i> and <i>in vivo</i> SERS measurements of Ag@Au-DTTC nanostars showed that the many sharp and narrow Raman peaks located at 508, 782, 844, 1135, 1242, 1331, 1464, 1510, and 1580 cm^–1 could be obviously observed in MCF-7 cells and in MCF-7 tumor-bearing nude mice, compared with that in pure DTTC. In 14-day treatments, the tumor volume of MCF-7 tumor-bearing nude mice injected with Ag@Au-DTTC nanostars and irradiated by an 808 nm laser almost disappeared. This study demonstrated that the as-prepared Ag@Au-DTTC nanostars could be excellent multifunctional agents for improved SERS imaging and NIR-triggered PTT of breast cancers with low risk

Immunohistochemistry staining of VEGF-C expression in the pleural tumors.

<p>Positive immunohistochemistry staining of VEGF-C was shown as brown part in each figure. Expression of VEGF-C was accessed by the percentage of positive carcinoma cells and the staining intensity. The positive staining of VEGF-C in NS group (A) and L-ES group (B) indicated high expression of VEGF-C in these groups. Low expression of VEGF-C was shown in Bevacizumab group (C) and H-ES group (D). The expression of VEGF-C was significantly decreased in H-ES group compared with that in NS group or L-ES group or Bevacizumab group.Columns: mean value of each group, bars: ±SD. ***P<0.001, **P<0.01, *P<0.05. ns: no significant difference.</p

Immunohistochemistry staining of VEGF-A expression in the pleural tumors.

<p>Positive immunohistochemistry staining of VEGF-A was shown as brown part in each figure. Expression of VEGF-A was accessed by the percentage of positive carcinoma cells and the staining intensity. The positive staining of VEGF-A in NS group (A) and L-ES group (B) indicated high expression of VEGF-A in these groups. Low expression of VEGF-A was shown in Bevacizumab group (C) and H-ES group (D). The expression of VEGF-A was significantly decreased in H-ES group compared with that in NS group or L-ES group, and there is no significant difference between Bevacizumab group and H-ES group (E). Columns: mean value of each group, bars: ±SD. ***P<0.001, **P<0.01, *P<0.05. ns: no significant difference.</p

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