Platelet-Mimicking Therapeutic System for Noninvasive Mitigation of the Progression of Atherosclerotic Plaques.

Atherosclerotic plaque is the primary cause of cardiovascular disorders and remains a therapeutic hurdle for the early intervention of atherosclerosis. Traditional clinical strategies are often limited by surgery-related complications or unsatisfactory effects of long-term drug administration. Inspired by the plaque-binding ability of platelets, a biomimic photodynamic therapeutic system is designed to mitigate the progression of atherosclerotic plaques. This system is composed of photosensitizer-loaded upconversion nanoparticle cores entrapped in the platelet membrane. The platelet membrane coating facilitates specific targeting of the therapeutic system to macrophage-derived foam cells, the hallmark, and main component of early stage atherosclerotic plaques, which is firmly confirmed by in vivo fluorescent and single-photon emission computed tomography/computed tomography (SPECT/CT) radionuclide imaging. Importantly, in vivo phototherapy guided by SPECT/CT imaging alleviates plaque progression. Further immunofluorescence analysis reveals foam cell apoptosis and ameliorated inflammation. This biomimic system, which combines plaque-binding with radionuclide imaging guidance, is a novel, noninvasive, and potent strategy to mitigate the progression of atherosclerotic plaque.

Effects of Dietary Phospholipids on Growth Performance, Digestive Enzymes Activity and Intestinal Health of Largemouth Bass (Micropterus salmoides) Larvae.

While the beneficial roles of dietary phospholipids on health status and overall performances of fish larvae have been well demonstrated, the underlying mechanisms remain unclear. To address this gap, the present study was conducted to investigate the effects of dietary phospholipids on growth performance, intestinal development, immune response and microbiota of larval largemouth bass (Micropterus salmoides). Five isonitrogenous and isolipidic micro-diets were formulated to contain graded inclusion levels of phospholipids (1.69, 3.11, 5.23, 7.43 and 9.29%). Results showed that the supplementation of dietary phospholipids linearly improved the growth performance of largemouth bass larvae. The inclusion of dietary phospholipids increased the activity of digestive enzymes, such as lipase, trypsin and alkaline phosphatase, and promoted the expression of tight junction proteins including ZO-1, claudin-4 and claudin-5. Additionally, dietary phospholipids inclusion alleviated the accumulation of intestinal triacylglycerols, and further elevated the activity of lysozyme. Dietary phospholipids inhibited the transcription of some pro-inflammatory cytokines, including il-1ß, and tnf-α, but promoted the expression of anti-inflammatory cytokines tgf-ß, with these modifications being suggested to be mediated by the p38MAPK/Nf-κB pathway. The analysis of bacterial 16S rRNA V3-4 region indicated that the intestinal microbiota profile was significantly altered at the genus level with dietary phospholipids inclusion, including a decreased richness of pathogenic bacteria genera Klebsiella in larval intestine. In summary, it was showed that largemouth bass larvae have a specific requirement for dietary phospholipids, and this study provided novel insights on how dietary phospholipids supplementation contributes to improving the growth performance, digestive tract development and intestinal health.

A Nd3+ sensitized upconversion nanosystem with dual photosensitizers for improving photodynamic therapy efficacy.

The efficacy of photodynamic therapy (PDT) was greatly hindered by the use of a 980 nm laser with undesired overheating effects as well as low reactive oxygen species (ROS) yields. Herein, we address these problems using a dual-photosensitizer (PS) loaded upconversion nanoparticle (UCNP) system. In detail, the NaYF4:Yb/Er/Nd@NaYF4:Nd core-shell UCNP system was designed to exhibit 808 nm laser excitation ability to avoid unfavorable thermal effects. More importantly, the co-encapsulation of dual PS, in terms of merocyanine 540 (MC540) and zinc phthalocyanine (ZnPc), could be respectively triggered by the dual emissions of UCNPs, which could generate sufficient ROS with improved efficiency. Furthermore, in vitro and in vivo studies were conducted to confirm the folate receptor (FR)-overexpressed cancer cell- or tumor-specific targeting ability with minimal side effects on normal tissue, by using this dual PS loaded UCNP system with the modification of the targeting group folic acid (FA). It is worth mentioning that the singlet oxygen production assay and PDT treatment demonstrated significantly enhanced PDT efficacy of the dual-PS approach, in comparison with the single PS method. In short, the FR-targeted dual-PS nanoconstructs maximized the anti-tumor efficacy of PDT by taking advantage of dual fluorescence emission and 808 nm excitation of UCNPs, which might inspire the future development of noninvasive deep-seated tumor treatment.