Platinum Nanoparticles-Enhanced Ferritin-Mn2+ Interaction for Magnetic Resonance Contrast Enhancement and Efficient Tumor Photothermal Therapy.

Nanoplatforms with high Mn2+ coordination can display efficient T1 magnetic resonance imaging (MRI) contrast enhancement. Herein, an earth gravity-like method for enhanced interaction between Ferritin (Fn) and Mn2+ by the growth of platinum nanoparticles (PNs) in Fn's cage structure via a biomineralization method is first proposed. Fn has good biocompatibility and can provide a suitable growth site for PNs. PNs with negative charge have certain attraction to Mn2+ with positive charge, improving Fn's loading capacity of Mn2+ by attraction force; and thus, achieving efficient MRI contrast enhancement. In addition, PNs can be applied for efficient photothermal therapy (PTT) under near infrared ray (NIR) irradiation. Systemic delivery of this nanoplatform shows obvious MRI contrast enhancement and tumor progression inhibition after NIR irradiation, as well as no obvious side effects. Therefore, this nanoplatform has the potential to contribute to nanotheranostic for clinical transformation.

CCR2-overexpressing biomimetic carrier-free nanoplatform for enhanced cascade ferroptosis tumor therapy.

Ferroptosis-based nanoplatforms have shown great potential in cancer therapy. However, they also face issues such as degradation and metabolism. Carrier-free nanoplatforms consisting of active drugs can effectively avoid the security issues associated with additional carrier ingredients. Herein, a biomimetic carrier-free nanoplatform (HESN@CM) was designed to treat cancer by modulating cascade metabolic pathways of ferroptosis. CCR2-overexpressing macrophage membrane-modified HESN can target cancer cells via the CCR2-CCL2 axis. The acidic tumor microenvironment (TME) can disrupt the supramolecular interaction of HESN, releasing hemin and erastin. Then, erastin could induce cancer cells ferroptosis by inhibiting system XC- pathways, while hemin, a vital component of blood to transport oxygen, could be broken down by heme oxygenase-1 (HO-1), increasing the intracellular Fe2+ concentration to induce cancer cells' ferroptosis further. Meanwhile, erastin could enhance the activity of HO-1, further promoting the release of Fe2+ from hemin. As a result, HESN@CM demonstrated superior therapeutic efficacy in both primary and metastatic tumors in vitro and in vivo. The carrier-free HESN@CM provided cascade ferroptosis tumor therapy strategies for potential clinical application. STATEMENT OF SIGNIFICANCE: CCR2-overexpressing biomimetic carrier-free nanoplatform (HESN@CM) was designed for cancer treatment by modulating metabolic pathways of ferroptosis. HESN modified with CCR2-overexpressing macrophage membrane can target tumor cells via the CCR2-CCL2 axis. HESN was composed of hemin and erastin without additional vectors. Erastin could directly induce ferroptosis, while hemin could be broken down by heme oxygenase-1 (HO-1), increasing the intracellular Fe2+ concentration to enhance ferroptosis further. Meanwhile, erastin could improve the activity of HO-1, promoting the release of Fe2+ from hemin. Therefore, HESN@CM with good bioavailability, stability, and simple preparation can realize cascade ferroptosis tumor therapy and have the potential prospect of clinical translation.

A pH-responsive liposomal nanoplatform for co-delivery of a Pt(IV) prodrug and cinnamaldehyde for effective tumor therapy.

Introduction: The tumor microenvironment (TME) is mainly characterized by abnormally elevated intracellular redox levels and excessive oxidative stress. However, the balance of the TME is also very fragile and susceptible to be disturbed by external factors. Therefore, several researchers are now focusing on intervening in redox processes as a therapeutic strategy to treat tumors. Here, we have developed a liposomal drug delivery platform that can load a Pt(IV) prodrug (DSCP) and cinnamaldehyde (CA) into a pH-responsive liposome to enrich more drugs in the tumor region for better therapeutic efficacy through enhanced permeability and retention effect. Methods: Using the glutathione-depleting properties of DSCP together with the ROS-generating properties of cisplatin and CA, we synergistically altered ROS levels in the tumor microenvironment to damage tumor cells and achieve anti-tumor effects in vitro. Results: A liposome loaded with DSCP and CA was successfully established, and this liposome effectively increased the level of ROS in the tumor microenvironment and achieved effective killing of tumor cells in vitro. Conclusion: In this study, novel liposomal nanodrugs loaded with DSCP and CA provided a synergistic strategy between conventional chemotherapy and disruption of TME redox homeostasis, leading to a significant increase in antitumor effects in vitro.

Shape programmable T1-T2 dual-mode MRI nanoprobes for cancer theranostics.

The shape effect is an important parameter in the design of novel nanomaterials. Engineering the shape of nanomaterials is an effective strategy for optimizing their bioactive performance. Nanomaterials with a unique shape are beneficial to blood circulation, tumor targeting, cell uptake, and even improved magnetism properties. Therefore, magnetic resonance imaging (MRI) nanoprobes with different shapes have been extensively focused on in recent years. Different from other multimodal imaging techniques, dual-mode MRI can provide imaging simultaneously by a single instrument, which can avoid differences in penetration depth, and the spatial and temporal resolution of multiple imaging devices, and ensure the accurate matching of spatial and temporal imaging parameters for the precise diagnosis of early tumors. This review summarizes the latest developments of nanomaterials with various shapes for T1-T2 dual-mode MRI, and highlights the mechanism of how shape intelligently affects nanomaterials' longitudinal or transverse relaxation, namely sphere, hollow, core-shell, cube, cluster, flower, dumbbell, rod, sheet, and bipyramid shapes. In addition, the combination of T1-T2 dual-mode MRI nanoprobes and advanced therapeutic strategies, as well as possible challenges from basic research to clinical transformation, are also systematically discussed. Therefore, this review will help others quickly understand the basic information on dual-mode MRI nanoprobes and gather thought-provoking ideas to advance the subfield of cancer nanomedicine.

Shield-activated two-way imaging nanomaterials for enhanced cancer theranostics.

Smart nanomaterials with stimuli-responsive imaging enhancement have been widely developed to meet the requirements of accurate cancer diagnosis. However, these imaging nanoenhancers tend to be always on during circulation, which significantly increases the background signal when assessing the imaging performance. To improve unfavorable signal-to-noise ratios, an effective way is to shield the noise signal of these nanoprobes in non-targeted areas. Fortunately, there is a natural mutual shielding effect between some imaging nanomaterials, which provides the possibility of designing engineered nanomaterials with imaging quenching between two different components at the beginning. Once in the tumor microenvironment, the two components will present activated dual-mode imaging ability because of their separation, designated as two-way imaging tuning. This review highlights the design and mechanism of a series of engineered nanomaterials with two-way imaging tuning and their latest applications in the fields of cancer magnetic resonance imaging, fluorescence imaging, and their combination. The challenges and future directions for the improvement of these engineered nanomaterials towards clinical transformation are also discussed. This review aims to introduce the special constraint relationships of imaging components and provide scientists with simpler and more efficient nanoplatform construction ideas, promoting the development of engineered nanomaterials with two-way imaging tuning in cancer theranostics.

Allicin regulates Treg/Th17 balance in mice with collagen-induced arthritis by increasing the expression of MEKK2 protein.

To study the role of Allicin in regulating Treg/Th17 ratio in splenic lymphocyte by increasing the expression of MEKK2 protein in MAPK signaling pathway, and to explore the mechanism of immune response in mice with collagen-induced arthritis (CIA). Mouse CIA model was induced by chicken collagen type II, and experimental mice were randomly divided into NC group, Model group, and Allicin group. HE staining was used to compare the degree of joint pathological damage in mice of each group, and Masson staining to observe the proliferation of collagen tissue in each group. Flow cytometry detected Treg/Th17 ratio in splenic lymphocytes. Furthermore, RT-PCR and WB were used to detect the mRNA and protein expression of related transcription factors and inflammatory factors Foxp3, ROR-γt, and IL-17A, as well as MEK2 protein expression in splenic lymphocytes. The results showed that Allicin treatment could reduce the severity of arthritis and the proliferation of collagen fibers on the surface of cartilage and bone joints in CIA mice. Compared with NC group, Treg decreased and Th17 increased in spleen lymphocyte of Model group (p < .01); after Allicin treatment, Treg increased while Th17 decreased significantly (p < .01). Meanwhile, MEKK2 protein expression in spleen lymphocyte of Model group decreased compared to that in NC group (p < .01), and MEK2 protein expression increased significantly after Allicin treatment (p < .01). To sum up, the present study suggests that MEKK2 protein plays an important role in the pathogenesis of CIA model. In terms of mechanism, Allicin may play a therapeutic role in rheumatoid arthritis (RA) by increasing the expression of MEKK2 protein and affecting Treg/Th17 ratio.

Comparative portrayal of ocular surface microbe with and without dry eye.

rRNA gene high-throughput sequencing was performed in the conjunctival swab samples to investigate the composition of the OS bacterial community in DE (n=35) and NDE (n=54) and compared the composition of MGD (n=25) and NMGD (n=10) among DE subjects. Deep sequencing of OS 16S rDNA from DE (n=35) and NDE (n=54) demonstrated great a difference in alpha and beta diversity between the OS bacterial flora (P < 0.05). The similar OS microbial structures were shown at the phylum and genus levels by bioinformatics analysis between them, and in LEfSe (linear discriminant analysis effect size) analysis, Bacteroidia and Bacteroidetes were enriched in DE, while Pseudomonas was plentiful in NDE (linear discriminant analysis [LDA] > 4.0). Among the DE group, there was no significant difference in α and ß diversity between MGD and NMGD (P > 0.05). Surprisingly, Bacilli was the dominant microbe in MGD, and Bacteroidetes was the superior bacteria in NMGD among DE subjects (LDA > 4.0). Different diversity of OS bacteria composition between DE and NDE and the altered diversity of OS bacteria may play an important role in DE. Moreover, the lower dominance of OS bacteria in DE may be associated with the occurrence and development of DE. Although there was no significant difference in alpha and beta analysis, the OS dominant microbe between MGD and NMGD among DE was different.

[Mutational analysis of EGFR and K-RAS in Chinese patients with non-small cell lung cancer].

OBJECTIVE: To investigate gene mutations of the epidermal growth factor receptor (EGFR) and K-RAS in Chinese non-small cell lung cancers (NSCLCs). METHODS: Mutations of exons 18, 19 and 21 of the EGFR and codons 12, 13 of the K-RAS in 101 NSCLCs were detected by PCR-amplifying and gene sequencing, and the relationship between mutations and clinical characters of NSCLCs and response to gefitinib were analyzed. RESULTS: Overall, 26 EGFR mutations (25.7%), 3 K-RAS mutations (2.9%) were detected, and EGFR mutation frequencies in adenocarcinomas, nonsmoker and female were found to be high (44.2%, 65.7% and 48.3% respectively). Nine out of 10 gefitinib treated patients with disease control was found with EGFR mutation. CONCLUSION: The data suggest that mutation frequency of EGFR in NSCLCs from Chinese patients is higher than that of western ethnicities, such mutations are well correlated with tumor response to gefitinib, and gefitinib is more fit for Chinese NSCLC patients.