Chloroplast-boosted photodynamic therapy for effective drug-resistant bacteria killing and biofilm ablation.

Due to the misuse of various antibiotics, the problem of bacterial resistance has become more serious worldwide, and the associated diseases have significantly increased the medical burden of society. Antimicrobial photodynamic therapy (PDT) has received widespread attention because of its safety, efficiency, and facile implementation. Here, we report an oxygen-supply antibacterial agent (Ce6@CS/CP), which could enhance the efficacy of antibacterial PDT via photosynthesis of O2. Ce6@CS/CP displayed a robust interaction with bacteria, hence facilitating the delivery efficiency of Ce6. In vitro experiments demonstrated that the photodynamic bactericidal potency of Ce6@CS/CP was remarkably greater than that of free Ce6. Furthermore, Ce6@CS/CP also exhibited superior significant antibiofilm activity to free Ce6. As a live oxygen-supply antibacterial agent, Ce6@CS/CP possesses excellent bacteria delivery ability of Ce6 and could enhance the potency of antibacterial PDT by photosynthesis, offering a new strategy for fighting against drug-resistant bacteria.

Sodium ferulate-functionalized silver nanopyramides with synergistic antithrombotic activity for thromboprophylaxis.

Thrombosis is one of the feared complications contributing to death in patients with cardiovascular diseases. Ferulic acid (FA), a bioactive compound extracted from traditional Chinese medicines, has drawn tremendous attention in prevention and treatment of thrombosis because of its notable antithrombotic potency. However, the poor aqueous solubility and pharmacokinetic profile of FA limit its clinical use. In this study, sodium ferulate-functionalized silver nanopyramides (SF-pAgNPs) with narrow size distribution were synthesized to overcome these obstacles and enhance the suppression effect of platelet activation and thrombosis formation. The cytotoxicity and hemolysis assays demonstrated that the prepared nanopyramides have a favorable biocompatibility pattern. In vitro studies revealed that SF-pAgNPs could effectively suppress platelet activation, aggregation and adhesion through the synergetic antithrombotic potential of SF and nano silver. Furthermore, SF-pAgNPs exhibited potent antithrombotic activity and prolonged inhibitory effect, much better than PEG-Ag and free SF in mouse model. With enhanced antithrombotic effect and acceptable biocompatibility, we believe the sodium ferulate-functionalized silver nanopyramides might hold the potential to be a promising strategy for the prevention and treatment of thrombosis.

Curcumin nicotinate suppresses abdominal aortic aneurysm pyroptosis via lncRNA PVT1/miR-26a/KLF4 axis through regulating the PI3K/AKT signaling pathway.

Abdominal aortic aneurysm (AAA) is a chronic dilated disease of the aorta that is characterized by chronic inflammation. Curcumin (Cur) is previously showed to attenuate AAA by inhibiting inflammatory response in ApoE -/- mice. Since Cur has the limitations of aqueous solubility and instability. Here, we focus on the role of curcumin nicotinate (CurTn), a Cur derivative is derived from Cur and nicotinate. An in vitro model of AAA was established by treating vascular smooth muscle cells (VSMCs) with II (Ang-II). Gene and protein expressions were examined by quantitative real-time PCR (qPCR) or western blotting. Cell migration and pyroptosis were determined by transwell assay and flow cytometry. The interaction between plasmacytoma variant translocation 1 (PVT1), miR-26a and krüppel-like factor 4 (KLF4) was predicted by online prediction tool and confirmed by luciferase reporter assay. CurTn reduced Ang-II-induced AAA-associated proteins, inflammatory cytokine expressions, and attenuated pyroptosis in VSMCs. PVT1 overexpression suppressed the inhibitory effect of CurTn on AngII-induced pyroptosis and inflammatory in VSMCs by sponging miR-26a. miR-26a directly targeted KLF4 and suppressed its expression, which eventually led to the deactivation of the PI3K/AKT signaling pathway. Besides, the regulatory effect of CurTn on pyroptosis of VSMCs induced by Ang-II was reversed through the PVT1/miR-26a/KLF4 pathway. In short, CurTn suppressed VSMCs pyroptosis and inflammation though mediation PVT1/miR-26a/KLF4 axis by regulating the PI3K/AKT signaling pathway, CurTn might consider as a potential therapeutic target in the treatment of AAA.

Decomposable black phosphorus nano-assembly for controlled delivery of cisplatin and inhibition of breast cancer metastasis.

Novel platforms for cisplatin delivery with a controllable manner and combinable with other treatment modality to achieve synergistic antitumor effect and inhibition metastasis for treatment of triple negative breast cancer (TNBC) are highly desirable. Herein, we report a black phosphorus (BP) nanosheets-based nano-assembly which consists of cisplatin, BP, polydopamine (PDA) and hyaluronic acid (HA), cisplatin/BP/PDA-HA (CBPH), for controlled delivery of cisplatin and inhibition tumor growth as well as lung metastasis of TNBC. For constructing CBPH, the surface of BP was dual modified by PDA and HA, resulting in enhanced stability, tumor target ability and photothermal efficiency of BP. Cisplatin was released in response both to internal and external stimuli existed in tumor microenvironment, including low pH, hydrogen peroxide and NIR light, as accompanied by decomposition of BP. In vitro experiments demonstrated CBPH-treated 4 T1 cells showed elevated intracellular content of Pt and Pt-DNA adduct, which was further improved when exposure to NIR light, leading to potent antitumor effect in a synergistic pattern. Anti-metastasis studies in 2D monolayers and 3D organoids revealed that CBPH plus NIR light treatment exhibited significantly decreased migration, invasion and regrowth ability of 4 T1 cells. Furthermore, TNBC-bearing mice with systemic administrate of CBPH showed enhanced tumor accumulation of cisplatin and light-triggered inhibition of tumor growth at primary site and lung metastasis, with alleviated toxicity. But CBPH is yet to be optimized for realizing smart cisplatin delivery in response to acidic and redox stimuli in vivo. Collectively, our study demonstrates that this novel BP-based nano-assembly with controllable tumor delivery of cisplatin and metastasis inhibition of breast cancer expand the use of BP in biomedicine field and hold great promise for further development.

Characterization of the nuclear import pathway for BLM protein.

Numerous studies have shown that nuclear localization of BLM protein, a member of the RecQ helicases, mediated by nuclear localization signal (NLS) is critical for DNA recombination, replication and transcription, but the mechanism by which BLM protein is imported into the nucleus remains unknown. In this study, the nuclear import pathway for BLM was investigated. We found that nuclear import of BLM was inhibited by two dominant-negative mutants of importin ß1 and NTF2/E42K, which lacks the ability to bind Ran and RanGDP, respectively, but was not inhibited by the Ran/Q69L, which is deficient in GTP hydrolysis. Further studies revealed that nuclear import of BLM was reconstituted using importin ß1, RanGDP and NTF2 in digitonin-permeabilized HeLa cells. Moreover, BLM had direct binding to importin ß1 through its NLS domain with the 14-16 HEAT repeats of importin ß1. Furthermore, importin ß1, Ran or NTF2 depletion by siRNA disrupted the accumulation of BLM protein in the nucleus. These results showed that BLM enters the nucleus via the importin ß1, RanGDP and NTF2 dependent pathway, demonstrating for the first time the nuclear trafficking mechanism of a DNA helicase.