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Ulcerative colitis(UC) is a recurrent, intractable inflammatory bowel disease. Coptidis Rhizoma and Bovis Calculus, serving as heat-clearing and toxin-removing drugs, have long been used in the treatment of UC. Berberine(BBR) and ursodeoxycholic acid(UDCA), the main active components of Coptidis Rhizoma and Bovis Calculus, respectively, were employed to obtain UDCA-BBR supramolecular nanoparticles by stimulated co-decocting process for enhancing the therapeutic effect on UC. As revealed by the characterization of supramolecular nanoparticles by field emission scanning electron microscopy(FE-SEM) and dynamic light scattering(DLS), the supramolecular nanoparticles were tetrahedral nanoparticles with an average particle size of 180 nm. The molecular structure was described by ultraviolet spectroscopy, fluorescence spectroscopy, infrared spectroscopy, high-resolution mass spectrometry, and hydrogen-nuclear magnetic resonance(H-NMR) spectroscopy. The results showed that the formation of the supramolecular nano-particle was attributed to the mutual electrostatic attraction and hydrophobic interaction between BBR and UDCA. Additionally, supramolecular nanoparticles were also characterized by sustained release and pH sensitivity. The acute UC model was induced by dextran sulfate sodium(DSS) in mice. It was found that supramolecular nanoparticles could effectively improve body mass reduction and colon shortening in mice with UC(P<0.001) and decrease disease activity index(DAI)(P<0.01). There were statistically significant differences between the supramolecular nanoparticles group and the mechanical mixture group(P<0.001, P<0.05). Enzyme-linked immunosorbent assay(ELISA) was used to detect the serum levels of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6), and the results showed that supramolecular nanoparticles could reduce serum TNF-α and IL-6 levels(P<0.001) and exhibited an obvious difference with the mechanical mixture group(P<0.01, P<0.05). Flow cytometry indicated that supramolecular nanoparticles could reduce the recruitment of neutrophils in the lamina propria of the colon(P<0.05), which was significantly different from the mechanical mixture group(P<0.05). These findings suggested that as compared with the mechanical mixture, the supramolecular nanoparticles could effectively improve the symptoms of acute UC in mice. The study provides a new research idea for the poor absorption of small molecules and the unsatisfactory therapeutic effect of traditional Chinese medicine and lays a foundation for the research on the nano-drug delivery system of traditional Chinese medicine.

Malignant tumor is still a leading threat to human health. Despite the rapid development of targeted therapeutic strategies, any treatment specifically acting on single target would inevitably suffer from tumor resistance, largely due to the genetic instability and variability of tumor cells. Thus, traditional therapies such as broad-spectrum chemotherapy would certainly occupy an important position in clinical cancer therapy. Nevertheless, most chemotherapeutic drugs have long been criticized for unsatisfactory therapeutic efficacy with severe off-target toxicity. Although several chemotherapeutic nanomedicines with improved therapeutic safety have been applied in clinics, the therapeutic outcomes still do not fulfill expectation. To address this challenge, enormous efforts have been devoted to developing novel nano-formulations for efficient delivery of chemotherapeutic drugs. Herein, we aim to outline the latest progression in the emerging nanomedicines of paclitaxel (PTX), with special attention to the functional nanocarriers, self-delivering prodrug-nanoassemblies and combination nanotherapeutics of PTX. Finally, the challenges and opportunities of these functional PTX nanomedicines in clinical translation are spotlighted., (Copyright © 2021. Published by Elsevier B.V.)

Objective: To construct a nanodelivery system surface-modified with RD2 peptide (polypeptide sequence PTLHTHNRRRRR) for brain tissue penetration and β-amyloid (Aβ) binding. Epigallocatechin-3-gallate (EGCG) was selected for encapsulation in the targeted delivery system and its therapeutic potential for Alzheimer's disease (AD) was investigated., Methods: EGCG-load nanoparticles (NP/EGCG), NP/EGCG with RD2 peptide surface modification (RD2-NP/EGCG), as well as RD2 peptide-modified blank nanoparticles (RD2-NP) were prepared and characterized. Thioflavin T assay was done to assess the ability of RD2-NP to bind with Aβ and ex vivo imaging was conducted to evaluate the distribution of RD2-NP in brain lesion sites. The AD mice model was established by injecting oligomeric Aβ 42 in the bilateral hippocampi of ICR mice. Then AD mice were administered intravenously through the tail vein with normal saline, EGCG solution, NP/EGCG or RD2-NP/EGCG for 28 d, respectively, and the Morris water maze tests were performed to assess the spatial memory of mice. Subsequently, RT-PCR method was used to determine the mRNA levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the hippocampus of the mice, and the morphological changes of hippocampal neurons were observed with Nissl staining. Additionally, the pathological changes of heart, liver, spleen, lung, and kidney were characterized by hematoxylin-eosin (HE) staining., Results: The particle diameter of the prepared RD2-NP/EGCG was (204.83±2.80) nm and the zeta potential was -23.88 mV. The encapsulation efficiency and drug loading capacity were 94.39% and 5.90%, respectively. The RD2 peptide modification has no significant effect on the physiochemical properties of the nanoparticles. RD2-NP had good Aβ binding ability, and it could be concentrated in hippocampus and cerebral cortex, the most common Aβ deposition sites. The four-week RD2-NP/EGCG treatment significantly decreased the expression of the pro-inflammatory cytokine TNF-α and IL-1β, restored neuronal losses and hippocampal damage, and ameliorated spatial memory impairment in AD model mice. Moreover, treatment with the RD2-NP/EGCG did not present organ toxicity., Conclusion: Surface modified RD2 peptide nanodelivery system can efficiently deliver drugs to AD lesions and improve the therapeutic effect of EGCG on AD., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Background: Characterization of early breast cancer circulating tumor cells (CTCs) may provide valuable information on tumor metastasis. Methods: We used immunomagnetic nanospheres to capture CTCs from the peripheral blood of eight early breast cancer patients and then performed single‐cell RNA sequencing using our proposed bead‐dd‐seq method. Results: CTCs displayed obvious tumor cell characteristics, such as the activation of oxidative stress, proliferation, and promotion of metastasis. CTCs were clustered into two subtypes significantly correlated with the lymph node metastasis status of patients. CTCs in subtype 1 showed a strong metastatic ability because these CTCs have the phenotype of partial epithelial‐mesenchymal transition and enriched transcripts, indicating breast cancer responsiveness and proliferation. Furthermore, DNA damage repair pathways were significantly upregulated in subtype 1. We performed in vitro and in vivo investigations, and found that cellular oxidative stress and further DNA damage existed in CTCs. The activated DNA damage repair pathway in CTCs favors resistance to cisplatin. A checkpoint kinase 1 inhibitor sensitized CTCs to cisplatin in mouse models of breast cancer metastasis. Conclusion: The present study dissects the molecular characteristics of CTCs from early‐stage breast cancer, providing novel insight into the understanding of CTC behavior in breast cancer metastasis. [ABSTRACT FROM AUTHOR]

SiO2 encapsulated quantum dots (QDs@SiO2) have been widely adopted for fabricating high-performance phosphor-converted light-emitting diodes (QCLEDs). However, the impact of SiO2 thickness on the optical properties of QDs in QCLEDs remains largely unexplored. In this work, we studied the combined effects of light scattering, heat accumulation, and concentration quenching of QD@SiO2 on optical performance of QCLEDs. QDs@SiO2 nanoparticles with SiO2 thickness of 10–60 nm were developed to perform the experimental tests and optical and thermal simulations. Our study reveals that at low power density, QD@SiO2 with 20–30-nm SiO2 shell display optimal efficiency owning to suppressed self-absorption quenching and enhanced light scattering. However, because of heat accumulation inside QDs@SiO2 at high power density, thin SiO2 shell (10–15 nm) is more favorable to reduce thermal quenching and maintain luminous efficiency of QCLEDs. This study provides guidance for the development of appropriate QDs@SiO2 structure to meet application requirements of different QCLED devices. [ABSTRACT FROM AUTHOR]