On-demand integrated nano-engager converting cold tumors to hot via increased DNA damage and dual immune checkpoint inhibition

Cancer immunotherapy has become a promising strategy. However, the effectiveness of immunotherapy is restricted in "cold tumors" characterized with insufficient T cells intratumoral infiltration and failed T cells priming. Herein, an on-demand integrated nano-engager (JOT-Lip) was developed to convert cold tumors to hot via "increased DNA damage and dual immune checkpoint inhibition" strategy. JOT-Lip was engineered by co-loading oxaliplatin (Oxa) and JQ1 into liposomes with T-cell immunoglobulin mucin-3 antibodies (Tim-3 mAb) coupled on the liposomal surface by metalloproteinase-2 (MMP-2)-sensitive linker. JQ1 inhibited DNA repair to increase DNA damage and immunogenic cell death (ICD) of Oxa, thus promoting T cells intratumoral infiltration. In addition, JQ1 inhibited PD-1/PD-L1 pathway, achieving dual immune checkpoint inhibition combining with Tim-3 mAb, thus effectively promoting T cells priming. It is demonstrated that JOT-Lip not only increased DNA damage and promoted the release of damage-associated molecular patterns (DAMPs), but also enhanced T cells intratumoral infiltration and promoted T cell priming, which successfully converted cold tumors to hot and showed significant anti-tumor and anti-metastasis effects. Collectively, our study provides a rational design of an effective combination regimen and an ideal co-delivery system to convert cold tumors to hot, which holds great potential in clinical cancer chemoimmunotherapy.

Research progress of drug delivery system based on black phosphorus in tumor diagnosis and treatment / 中国药科大学学报

@#As a new member of two-dimensional materials, black phosphorus has shown good application prospects in the fields of photoacoustic imaging, photothermal photodynamic therapy, and drug loading due to its excellent characteristics such as good biodegradability, biocompatibility, thickness-dependent tunable direct band-gap, and high surface-to-mass ratio. Because black phosphorus has the characteristics of easy oxidation and degradation, it is coated with relatively stable liposomes or polymeric materials to construct a black phosphorus-based drug delivery system, which shows great potential in tumor treatment and diagnosis and has become a new focus in drug delivery research. In this paper, we introduce the role of black phosphorus in tumor diagnosis and treatment in detail, and summarize the design of black phosphorus-based drug delivery system in recent years as well as its research progress in tumor diagnosis and treatment, in order to provide reference for the research and application of black phosphorus.

Endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis of non-lymph node thoracic lesions

Endobronchial ultrasound-guided transbronchial needle aspiration [EBUS-TBNA] has shown excellent diagnostic capabilities for mediastinal and hilar lymphadenopathy. However, its value in thoracic non-lymph node lesions is less clear. This study was designed to assess the value of EBUS-TBNA in distinguishing malignant from benign thoracic non-lymph node lesions. From October 2009 to August 2011, 552 patients underwent EBUS-TBNA under local anesthesia and with conscious sedation. We retrospectively reviewed 81 of these patients who had tracheobronchial wall-adjacent intrapulmonary or isolated mediastinal non-lymph node lesions. On-site cytological evaluation was not used. Immunohistochemistry [IHC] was performed to distinguish the origin or type of malignancy when necessary. EBUS-TBNA was performed in 68 tracheobronchial wall-adjacent intrapulmonary and 13 isolated mediastinal non-lymph node lesions. Of the 81 patients, 77 [95.1%, 60 malignancies and 17 benignancies] were diagnosed through EBUS-TBNA, including 57 primary lung cancers, 2 mediastinal tumors, 1 pulmonary metastatic adenocarcinoma, 7 inflammation, 5 tuberculosis, 3 mediastinal cysts, 1 esophageal schwannoma, and 1 focal fibrosis. There were four false-negative cases [4.9%]. Of the 60 malignancies, there were 9 [15.0%] which originally had no definite histologic origin or type. Thus, IHC was performed, with 7 [77.8%] being subsequently confirmed. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of EBUS-TBNA in distinguishing malignant from benign lesions were 93.4% [60/64], 100% [17/17], 100% [60/60], 81.0% [17/21], and 95.1% [77/81], respectively. EBUS-TBNA is a safe procedure with a high sensitivity for distinguishing malignant from benign thoracic non-lymph node lesions within the reach of EBUS-TBNA, with IHC usually providing a more definitive diagnosis

ANALYSIS OF PROTEINS AND ANTIGENS IN NINE STRAINS OF TOXOPLASMA GONDII BY MEANS OF SDS-PAGE AND IMMUNOBLOTTING / 中国寄生虫学与寄生虫病杂志

The proteins and antigens of nine strains of Toxoplasma gondii were analyzed by SDS-PAGE and immunoblotting. These strains including RH strain, Zs-2 strain, CN strain and SHI, SH2, SH3, SH4, SH5, SH8 strains, were obtained from other laboratories or isolated from deformity fetus in our laboratory. SDS-PAGE analysis revealed that these strains were very close in the major bands of proteins and differences were observed only in part. There were common components in antigens of all strains using IgG antibody prepared from high-titre rabbit antisera raised against RH strain of Toxoplasma.