Sphingosine-1-Phosphate Receptor Targeted PLGA Nanobubbles for Inflammatory Vascular Endothelial Cell Catching.

Vascular inflammation is an early manifestation and common pathophysiological basis of numerous cardiovascular and cerebrovascular diseases. However, effective surveillance methods are lacking. In this study, sulfur hexafluoride (SF6 )-loaded polylactic acid-co-glycolic acid (PLGA) nanobubbles (NBs) with a surface assembly of cyclodextrin (CD) and sphingosine-1-phosphate (S1P) (S1P@CD-PLGA NBs) are designed. The characterization results show that S1P@CD-PLGA NBs with diameters of ≈200 nm have good stability, biosafety, and ultrasound imaging-enhancement effects. When interacting with inflammatory vascular endothelial cells, S1P molecules encapsulated in cyclodextrin cavities exhibit a rapid, excellent, and stable targeting effect owing to their specific interaction with the highly expressed S1P receptor 1 (S1PR1) on the inflammatory vascular endothelial cells. Particularly, the S1P-S1PR1 interaction further activates the downstream signaling pathway of S1PR1 to reduce the expression of tumor necrosis factor-α (TNF-α) to protect endothelial cells. Furthermore, mouse models of carotid endothelial injuries and mesenteric thrombosis demonstrate that S1P@CD-PLGA NBs have excellent capabilities for in vivo targeting imaging. In summary, this study proposes a new strategy of using S1P to target inflammatory vascular endothelial cells while reducing the expression of TNF-α, which has the potential to be utilized in the targeted surveillance and treatment of vascular inflammatory diseases.

pH/Thermal-Sensitive Nanoplatform Capable of On-Demand Specific Release to Potentiate Drug Delivery and Combinational Hyperthermia/Chemo/Chemodynamic Therapy.

Therapeutic platforms with spatiotemporal control were recently of considerable interest. However, the site-specific regulation of chemotherapeutics release remains an enormous challenge. Herein, a versatile nanoplatform capable of tumor-specific delivery and controlled drug release, coined as PDDFe, was constructed for elevating cancer theranostics. Iron-oxide nanoparticles (IONPs) and doxorubicin (Dox) were encapsulated in pH/thermal-sensitive micelles composed of poly(ethylene)glycol-poly(ß-amino esters) and dipalmitoyl phosphatidylcholine to obtain tumor-targeted dual-responsive nanoplatforms. With remarkable magnetic targeting effects, PDDFe specifically accumulated at tumor locations. After internalization by cancer cells, the acidic environment and localized heat generated by hyperthermia therapy would spur PDDFe to become loose and collapse to liberate its payload. In addition to boosting the release, the increased temperature also resulted in direct tumor damage. Meanwhile, the released Dox and IONPs, respectively, stimulated chemotherapy and chemodynamic therapy to jointly destroy cancer, thus leading to a pronounced therapeutic effect. In vivo magnetic resonance/fluorescence/photoacoustic imaging experiments validated that the dual-sensitive nanoplatforms were able to accumulate at the tumor sites. Treatment with PDDFe followed by alternating magnetic field and laser irradiation could prime hyperthermia/chemo/chemodynamic therapy to effectively retard tumor growth. This work presents a nanoplatform with a site-specific controlled release characteristic, showing great promises in potentiating drug delivery and advancing combinational cancer therapy.

Research progress of autophagy in viral pneumonia / 中国临床药理学与治疗学

Autophagy, as a highly conserved process of recovery and degradation of eukaryotic components, plays an important role in cell hunger response, maintenance of normal cell activity and specific functions in lung tissue. When cells are damaged due to physiological, pathological or chemical factors, autophagosomes and lysosomes fuse to produce a large number of autophagosomes, thus inducing the initiation of autophagy process, which is beneficial to protect cells from injury. Recent studies have found that autophagy related signaling pathways are highly correlated with the occurrence and development of a variety of viral pneumonia, such as swine influenza A (H1N1) virus, highly pathogenic avian influenza virus (H5N1), severe acute respiratory syndrome (SARS), middle east respiratory syndrome (MERS) and new coronavirus pneumonia (COVID-19). This paper will introduce the five viral pneumonia that have a great impact on China and even the whole world, and elaborate the mechanism of autophagy in these disease. Hopefully it could provide theoretical basis and effective methods and means for targeted autophagy treatment of viral pneumonia.

Study on Preparation and in vitro Anticancer Activity of PFV-modified Paclitaxel/artesunate Co-loaded Targeting Micelles / 中国药房

OBJECTIVE：To prepare cell penetrating peptide PFV-modified paclitaxel （PTX）/artesunate（ART）co-loaded targeting micelles ，and to investigate in vitro anti-tumor activity. METHODS ：According to optimal technology ，PFV-modified PTX/ ART co-loaded targeting micelles were prepared by membrane hydration method ，and were characterized. Using blank micelle as blank control ，sulforhodamine B （SRB）method was used to evaluate the toxicity of PTX micelles ，ART micelles ，PTX/ART micelles and PFV-modified PTX/ART co-loaded targeting micelles to human gastric cancer BGC- 823 cells. The coumarin was used as fluorescent probe replacing PTX to prepare corresponding micelles. Then ，the uptake of BGC- 823 cells to corresponding micelles and targeting effect were observed and determined by flow cytometry and fluorescence microscope. The effects of PTX micelles ， ART micelles ，PTX/ART micelles and PFV-modified PTX/ART co-loaded targeting micelles on the invasion of BGC- 823 cells were investigated by Transwell chamber method. RESULTS ：Average particle size of PFV-modified PTX/ART co-loaded targeting micelles was （51.30±3.95）nm；PDI was 0.19±0.01，and Zeta potential was （0.21±0.02）mV. The encapsulation efficiency of PTX and ART were higher than 90％. The shape of micelles were spherical. The blank micelles had no obvious toxicity to BGC-823 cells. The IC 50 value of PTX micelles ，PTX/ART micelles and PFV-modified PTX/ART co-loaded targeting micelles to BGC-823 cells were （3.09±0.22），（1.93±0.24），（1.11±0.15）μmol/L，respectively. The distribution amount of different micelles in BGC- 823 cell nucleus in the descending order were PFV-modified coumarin/ART micelles ＞coumarin/ART micelles ＞coumarin micelles＞blank control. The order of inhibitory effect was PFV-modified PTX/ART co-loaded targeting micelles ＞PTX/ART micelles＞ART micelles ＞PTX micelles ＞blank control. CONCLUSIONS： Prepared PFV-modified PTX/ART No.81874347） co-loaded targeting micelles are in line with the quality of 1915286446@qq.com Chinese Pharmacopoeia . It shows strong cytotoxicity to BGC-823 cells，can improve the drug targeting and the cell uptake，and inhibit the inv asion and metastasis of BGC- 823 cells.

Recognition Sites for Cancer-targeting Drug Delivery Systems.

BACKGROUND: Target-homing drug delivery systems are now gaining significant attention for use as novel therapeutic approaches in antitumor targeting for cancer therapy. Numerous targeted drug delivery systems have been designed to improve the targeting effects because these systems can display a range of favorable properties, thus, providing suitable characteristics for clinical applicability of anticancer drugs, such as increasing the solubility, and improving the drug distribution at target sites. The majority of these targeting systems are designed with respect to differences between cancerous and normal tissues, for instance, the low pH of tumor tissues or overexpressed receptors on tumor cell membranes. Due to the growing number of targeting possibilities, it is important to know the tumor-specific recognition strategies for designing novel, targeted, drug delivery systems. Herein, we identify and summarize literature pertaining to various recognition sites for optimizing the design of targeted drug delivery systems to augment current chemotherapeutic approaches. OBJECTIVE: This review focuses on the identification of the recognition sites for developing targeted drug delivery systems for use in cancer therapeutics. METHODS: We have reviewed and compiled cancer-specific recognition sites and their abnormal characteristics within tumor tissues (low pH, high glutathione, targetable receptors, etc.), tumor cells (receptor overexpression or tumor cell membrane changes) and tumor cell organelles (nuclear and endoplasmic reticular dysregulation) utilizing existing scientific literature. Moreover, we have highlighted the design of some targeted drug delivery systems that can be used as homing tools for these recognition sites. RESULTS AND CONCLUSION: Targeted drug delivery systems are a promising therapeutic approach for tumor chemotherapy. Additional research focused on finding novel recognition sites, and subsequent development of targeting moieties for use with drug delivery systems will aid in the evaluation and clinical application of new and improved chemotherapeutics.

Pharmacokinetics and tissue distribution study in rats of asiaticoside-loaded modified liposomes / 中草药

Objective To prepare asiaticoside-loaded modified liposomes and to investigate the distribution and pharmacokinetics. Methods Different asiaticoside-loaded preparations (include solution, modified, and unmodified liposomes) were injected by tail vein in SD rats. HPLC method was used to detect the concentration of asiaticoside in the tissue and plasma samples. And the concentration-time profiles and pharmacokinetic parameters were then obtained and compared to get the variances. Results The concentration-time profiles of asiaticoside-loaded preparations guided along the single compartment model which the weight is 1/C2. The elimination half-life of asiaticoside solution and different asiaticoside liposomes were (14.52 ± 0.56), (101.35 ± 12.47), (149.82 ± 20.00), and (159.58 ± 16.46) min, respectively. The AUC of asiaticoside solution and different asiaticoside liposomes were (1 929.70 ± 159.00), (57 004.35 ± 8 710.89), (93 736.52 ± 12 710.76), and (64 737.48 ± 6 365.28) min∙μg/mL, respectively. The mass fraction of asiaticoside in each organ increased, especially in the pulmonary which increased from (4.94 ± 0.94) μg/g to (39.12 ± 12.04) μg/g. Conclusion The sustained release and targeting effects in SD rats were obvious of the asiaticoside-loaded modified liposomes.