Exosomes are small endogenous membrane vesicles that can mediate cell communication by transferring genetic materials. Based on that, exosomes have always been discussed as a cargo carrier for microRNA (miRNA) transportation. Accumulating data have reported the inhibitory effects of microRNA-193a (miR-193a) on non-small cell lung cancer (NSCLC) cell progression. However, the mechanisms of miR-193a delivery to cancer cells and miR-193a in exosomes have not been explored clearly in NSCLC. Given that, this work aims to decode exosomal miR-193a in cisplatin (DDP) resistance of NSCLC cells. A549 and H1299 cell lines were screened out and their parent cells and drug-resistant cells were co-cultured with human bone marrow mesenchymal stem cells (BMSCs)-derived exosomes (BMSC-Exo) that had been transfected with miR-193a mimic or si-LRRC1 to detect the colony formation, migration, apoptosis, invasion and proliferation of NSCLC cells. In vivo experiment was conducted to verify the in vitro results. BMSC-Exo with upregulated miR-193a and downregulated LRRC1 suppressed colony formation, invasion, proliferation and migration as well as advanced apoptosis of NSCLC parent cells and drug-resistant cells. BMSC-Exo combined with upregulated miR-193a reduced tumor volume and weight in mice with NSCLC. Functional studies report that BMSC-Exo shuffle miR-193a to suppress the colony formation, invasion, migration, and proliferation as well as advance apoptosis of NSCLC DDP-resistant cells via downregulating LRRC1.

Biomimetic cell membrane coated nanoparticles (NPs) with desirable features have been extensively applied for various personalized biomedicine. However, there have not been relative explorations by employing the membrane nanocomplexes for small interfering RNA (siRNA) delivery. Herein, Fe 3 O 4 @PDA NPs with good photothermal capability were applied for efficient siRNA loading and delivery, which were then coated by mesenchymal stem cells (MSCs) to form a membrane. The data showed that MSCs membrane coated Fe 3 O 4 @PDA−siRNA NPs (Fe 3 O 4 @PDA−siRNA@MSCs) maintained the photothermal functionality and the capability of magnetic resonance imaging inherited from Fe 3 O 4 @PDA. The synthesized nanocomplexes exhibited excellent abilities in the delivery of siRNA into DU145 cells. Furthermore, Fe 3 O 4 @PDA−siRNA@MSCs NPs delivering siRNA against Plk1 gene could inhibit the expression of endogenous Plk1 gene and cause obvious apoptosis in DU145 cells. The synergistic combination of photothermal treatment and gene silencing showed obvious antitumor efficacy in a DU145 xenograft mice model. On the basis of preliminary in vitro and in vivo studies, Fe 3 O 4 @PDA−siRNA@MSCs NPs hold considerable promise as a carrier for gene and photothermal therapy.

This multicenter phase-II trial aimed to investigate the efficacy, safety, and predictive biomarkers of toripalimab plus chemotherapy as second-line treatment in patients with EGFR-mutant-advanced NSCLC. Patients who failed from first-line EGFR-TKIs and did not harbor T790M mutation were enrolled. Toripalimab plus carboplatin and pemetrexed were administrated every three weeks for up to six cycles, followed by the maintenance of toripalimab and pemetrexed. The primary endpoint was objective-response rate (ORR). Integrated biomarker analysis of PD-L1 expression, tumor mutational burden (TMB), CD8 + tumor-infiltrating lymphocyte (TIL) density, whole-exome, and transcriptome sequencing on tumor biopsies were also conducted. Forty patients were enrolled with an overall ORR of 50.0% and disease-control rate (DCR) of 87.5%. The median progression free survival (PFS) and overall survival were 7.0 and 23.5 months, respectively. The most common treatment-related adverse effects were leukopenia, neutropenia, anemia, ALT/AST elevation, and nausea. Biomarker analysis showed that none of PD-L1 expression, TMB level, and CD8 + TIL density could serve as a predictive biomarker. Integrated analysis of whole-exome and transcriptome sequencing data revealed that patients with DSPP mutation had a decreased M2 macrophage infiltration and associated with longer PFS than those of wild type. Toripalimab plus chemotherapy showed a promising anti-tumor activity with acceptable safety profiles as the second-line setting in patients with EGFR-mutant NSCLC. DSPP mutation might serve as a potential biomarker for this combination. A phase-III trial to compare toripalimab versus placebo in combination with chemotherapy in this setting is ongoing (NCT03924050).

Polydopamine nanoparticles camouflaged with stem cell membranes could effectively target tumor sites and showed excellent performance in synergistic chemoimmunotherapy for PCa bone metastases.

Late embryogenesis abundant (LEA) proteins are involved in the responses and adaptation of plants to various abiotic stresses, including dehydration, salinity, high temperature, and cold. Here, we report the first comprehensive survey of the LEA gene family in “Chinese Spring” wheat (Triticum aestivum). A total of 179 TaLEA genes were identified in T. aestivum and classified into eight groups. All TaLEA genes harbored the LEA conserved motif and had few introns. TaLEA genes belonging to the same group exhibited similar gene structures and chromosomal locations. Our results revealed that most TaLEA genes contained abscisic acid (ABA)-responsive elements (ABREs) and various cis-acting elements associated with the stress response in the promoter region and were induced under ABA and abiotic stress treatments. In addition, 8 genes representing each group were introduced into E. coli and yeast to investigate the protective function of TaLEAs under heat and salt stress. TaLEAs enhanced the tolerance of E. coli and yeast to salt and heat, indicating that these proteins have protective functions in host cells under stress conditions. These results increase our understanding of LEA genes and provide robust candidate genes for future functional investigations aimed at improving the stress tolerance of wheat.

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Multifunctional nanocomposites that have multiple therapeutic functions together with real-time imaging capabilities have attracted intensive concerns in the diagnosis and treatment of cancer. This study developed epidermal growth factor receptor (EGFR) antibody-directed polydopamine-coated Fe 3 O 4 nanoparticles (Fe 3 O 4 @PDA NPs) for magnetic resonance imaging and antitumor chemo-photothermal therapy. The synthesized Fe 3 O 4 @PDA-PEG-EGFR-DOX NPs revealed high storage capacity for doxorubicin (DOX) and high photothermal conversion efficiency. The cell viability assay of Fe 3 O 4 @PDA-PEG-EGFR NPs indicated that Fe 3 O 4 @ PDA-PEG-EGFR NPs had no cell cytotoxicity. However, Fe 3 O 4 @PDA-PEG-EGFR-DOX NPs could significantly decrease cell viability (~5% of remaining cell viability) because of both photothermal ablation and near-infrared light-triggered DOX release. Meanwhile, the EGFR-targeted Fe 3 O 4 @PDA-PEG-EGFR-DOX NPs significantly inhibited the growth of tumors, showing a prominent in vivo synergistic antitumor effect. This study demonstrated the potential of using Fe 3 O 4 @PDA NPs for combined cancer chemo-photothermal therapy with increased efficacy.

In our study, a silica-polymer composite nano system (MB-NSi-p53-CS ternary complexes) composed of methylene blue-encapsulated amine-terminated silica nanoparticles (MB-NSi) and chondroitin sulfate (CS) were successfully developed for tumor-targeted imaging and p53 gene therapy of lung cancer. MB was employed as a NIR probe for in vivo imaging, MB-NSi nanoparticles were served as gene vector, while CS was applied to be a coating and targeting polymer. MB-NSi-p53-CS ternary complexes displayed nanosized diameter, effective p53 condensation ability, efficient p53 protection profile, and superior bovine serum albumin stability in vitro. Experiments on A549 cell line further revealed low cytotoxicity, high p53 transfection, and anticancer efficacy of MB-NSi-p53-CS ternary complexes. In vivo imaging and tumor targetability assays demonstrated that MB-NSi-p53-CS ternary complexes were a preferable system with desirable imaging and tumor-targeting properties.