Inspired by the coordination effects between imidazole and metal ions in hemoglobin, biomimetic nanoparticles were constructed for photodynamic tumor therapy. The photosensitizer of protoporphyrin IX (PpIX) was modified with histidine, which could be self-assembled with Zn²⁺ to obtain the biomimetic nanoparticles (NPs). Under the conditions of high glutathione and low pH, the biomimetic nanoparticles could be degraded and released for enhanced photodynamic tumor therapy. The structures of NPs were characterized by dynamic light scattering (DLS), UV-visible spectrophotometer (UV-Vis), fluorescence microscope and transmission electron microscope (TEM). The reactive oxygen species (ROS) production ability of NPs was measured by singlet oxygen sensor green (SOSG) test kit. Mouse breast cancer cell lines (4T1 cells) were employed to investigate the subcellular organelle distribution and cytotoxicity of NPs. These results confirmed that NPs possessed a good dispersibility and stability with a uniform structure and particle size at 165 nm. Moreover, MTT assay and live/dead cell staining assay demonstrated that NPs could inhibit the proliferation of 4T1 cells and exhibit a good biocompatability. This research would promote the construction of intelligent biomedicine for tumor precision therapy.

Cardiac glycoside is a class of steroidal glycosides with significant physiological activities to the heart. Several drugs had been approved for the treatment of heart failure and atrial fibrillation. In recent studies, the researchers have found that cardiac glycoside can selectively inhibit the proliferation of human tumor cells and has potent antitumor efficacy. Unfortunately, the poor solubility and severe adverse effects of cardiac glycoside hindered further clinical application in the field of anticancer. It is an effective strategy to solve the "drug-like" problem of cardiac glycoside by changing the pharmacokinetics and distribution in vivo and reducing the dosage and side effects by virtue of modern preparations technology and treatment scheme. In this review, a brief introduction of the developmental course and mechanism of cardiac glycosides in anticancer field was made, and recent research progress of cardiac glycosides preparations were summarized and discussed. Finally, the further research direction was prospected.

Diabetes is characterized by hyperglycemia, resulting from insulin deficiency or resistance, or both. Insulin plays an irreplaceable role in the treatment of diabetes. Subcutaneous injection is the main route of insulin administration, but usually leads to poor compliance and many side effects. Oral insulin is safer and more convenient, which has always been the Holy Grail for people to explore. After oral administration, insulin is absorbed into the hepatic portal vein and transported to the liver, which can activate the normal physiological functions and reduce the risk of hypoglycemia, insulin resistance, and improve patient compliance. However, the gastrointestinal tract has multiple absorption barriers such as chemical barrier, enzyme barrier, and permeation barrier. Due to the physical and chemical properties of insulin, it is difficult to achieve desired oral bioavailability. This article reviews the recent attempts and progress in the field of oral administration of insulin driven by innovative drug delivery technologies and biomaterials, including structural modification, enzyme inhibitors, absorption enhancers, various nanoparticles, liposomes, microspheres, and even microorganisms. Some clinical researches on oral insulin are also introduced.

Exosomes are disk-shaped vesicles with a diameter of 40-100 nm, which are composed of natural lipid bilayers. Most cells can produce exosomes, which play an important role in physiological and pathological processes, affecting signal pathways, intercellular communication, tumor progression and molecular metastasis. Exosomes are characterized by low immunogenicity, good natural stability, long half-life, high delivery efficiency, and the ability to cross the blood-brain barrier, which can be used as a good carrier for drug delivery. This review focuses on the research progress of exosomes as drug delivery systems in the treatment of brain diseases, such as central nervous system degenerative diseases, brain tumors and cerebrovascular diseases and so on.

In recent years, the incidence and mortality of invasive fungal infections has increased. It is highly desirable to develop novel antifungal agents with new modes of action. Targeting virulence factors represents a new strategy for antifungal drug discovery. Secreted aspartic protease 2 (SAP2), a kind of virulence factor, is an emerging antifungal target. However, discovery of small-molecule SAP2 inhibitors remains a significant challenge. Based on the structure-activity relationship of our previously identified triazine small-molecule SAP2 inhibitor, we were able to identify two potent inhibitors, 8a and 8c, which showed excellent in vivo antifungal activity for the treatment of C. albicans infection. Moreover, compounds 8a and 8b effectively inhibited fungal biofilm. Taken together, triazine SAP2 inhibitors represent promising lead compounds for the discovery of novel antifungal agents.

Most of the active ingredients of herbs are secondary metabolites of plants. Cytochrome P450s (P450s) are hemoglobin-containing monooxygenases encoded by a super-gene family, which play important roles in the metabolic network of plants. This review focuses on the role of P450s on biosynthesis of secondary metabolites such as terpenoids, alkaloids, flavonoids and phenylpropanoids. This will provide references for biosynthesis and regulation of secondary metabolites in medicinal plants.

To date, CRISPR/Cas systems represent the most widely used tool for genome editing; however, its application scope for gene therapy has been largely limited due to its limited efficiency in activating homologydirected repair for DNA and off-target effect. Base editing is a new CRISPR/Cas-based genome-editing strategy, which allows single nucleotide to be precisely corrected in a narrow window scope on the target DNA or RNA by taking advantage of different nucleobase deaminases. Base editors include cytosine base editors (CBEs) and adenine base editors (ABEs), which can induce the conversions from C·G to T·A and A·T to G·C, respectively. Base editors work independently of double-strand DNA breaks (DSBs) and DNA donor templates, and thus they are extensively adopted for a wide range of therapeutic applications for genetic diseases, largely owing to their high efficiency and great specificity. In this review, we summarize the development of base editors and their potentials as therapeutic drugs for treating genetic diseases, and future outlooks are also discussed.

To target neovasculature and tumor cells, a novel cationic liposome with verteporfin (BPD) active-loaded in lumen (CLL) was designed and its basic in vitro and in vivo behaviors were evaluated in this study. Calcium acetate gradient loading method was applied to encapsulate BPD actively and cationic lipid (2, 3-dioleoy-loxy-propyl)-trimethylammonium (DOTAP) was added by post-insertion for the positive charge of CLL. Results of characterization showed that the diameter and zeta-potential of CLL were around 100 nm and 28 mV, respectively. Compared with passive loading liposomes, CLL significantly enhanced the stability of BPD loading. What's more, the loaded BPD in lumen could switch off the fluorescence and photosensitization during blood circulation by homo-fluorescence resonance energy transfer (homo-FRET) effect, leading to the diminished phototoxicity to normal tissues. In vitro cellular uptake and cytotoxicity assay exhibited that positive charge dramatically enhanced the uptake of CLL both in vascular endothelial cells and tumor cells leading to superior therapeutic efficacy. In vivo study further showed that CLL reduced the clearance rate and increased tumor accumulation compared with passive loading group. Quantitative results of exvivo organ indicated that negligible CLL distributed in normal organs contributing to low phototoxicity. Animal experiments were conducted according to the Guidelines of the Experimental Animal Ethics Committee of Peking University Health Science Center and International Animal Experiments. In conclusion, we successfully designed a novel cationic targeting liposome that overcame the limitations of passive loading and significantly enhanced the efficacy of photodynamic therapy.

In this study, the model of Propionibacterium acnes/lipopolysaccharide (P. acnes/LPS)-induced acute liver injury in mice was employed to investigate the protective effects of Fuzheng Yanggan Fomula (FYF) on acute liver injury. The effects of FYF on the contents of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and interleukin-1β (IL-1β) in the serum, and the levels of malondialdehyde (MDA), oxygen radical absorbance capacity (ORAC), and glutathione (GSH) were examined in the livers of mice treated with P. acnes/LPS; The protein expression levels of Nod-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), cysteinyl aspartate specific proteinase-1 (caspase-1), and IL-1β in liver tissues were detected by Western blot; Furthermore, hematoxylinendash-eosin (HE) staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and immunohistochemical assay were used to observe pathological changes, apoptosis index, and inflammation infiltration of the liver tissue sections. All animal welfare and experimental procedures were followed by the Animal Ethics Committee of Jinan University. We conclude that FYF could alleviate P. acnes/LPS induced pathological damage and inflammatory infiltration in the liver of mice. Meanwhile, FYF decreases the contents of ALT, AST, IL-1β, and MDA, increases the contents of ORAC and GSH, and downregulates the expression of caspase-1 and IL-1β proteins. Collectively, these findings suggested that FYF could alleviate P. acnes/LPS induced acute liver injury in mice by inhibiting the activation of NLRP3 inflammasome, which provides a theoretical basis and a new drug target for the prevention and treatment of liver injury.

This research investigated the effect of parthenolide on the proliferation and migration of human breast cancer cells and explored the molecular mechanism of that effect. Surface plasmon resonance and fluorescence resonance energy transfer melting were used to detect the binding and stabilizing ability of PTL and G-quadruplex. MTT assays were used to determine the effect of PTL on the proliferation of MCF-7 breast cancer cells. A wound healing assay was performed to detect the migration of MCF-7. The results indicate that PTL shows good binding and stabilizing activities with c-myc G-quadruplex with a K_D=13.1 μmol·L^-1. PTL inhibited the proliferation of MCF-7 cells with an IC₅₀ of 21.3 μmol·L^-1 (24 h), 14.5 μmol·L^-1 (48 h) and 9.1 μmol·L^-1 (72 h). PTL inhibited MCF-7 breast cancer cell proliferation and migration and down-regulated the transcription and expression level of c-myc by targeting G-quadruplex.