Maleimide-Functionalized Liposomes for Tumor Targeting via In Situ Binding of Endogenous Albumin

Albumin, the most abundant protein in plasma, has been widely used in drug delivery studies. Here, we developed maleimide-functionalized liposomes (Mal-Lip) that can bind to endogenous albumin to improve the tumor targeting efficiency of liposomes. Transmission electron microscopy and gel electrophoresis studies showed that albumin can bind to Mal-Lip due to the chemical coupling of the albumin thiol groups with the maleimide group. Both conventional liposomes and Mal-Lip showed minimal cytotoxicity within the tested range of lipid concentrations, indicating that the maleimide functionality did not increase the toxicity of liposomes to various cells. Mal-Lip was taken up by 4T1 cells to a greater extent than conventional liposomes, and Mal-Lip accumulated in 4T1 tumors in mice more than conventional liposomes after intravenous injection. These results suggest that the maleimide group can improve the tumor targeting efficiency of liposomes in vivo by binding to endogenous albumin in situ. However, the maleimide group also enhanced the uptake of Mal-Lip by Raw264.7 cells and shortened their time in circulation, indicating that further studies should be performed to prevent elimination of Mal-Lip by the immune system.

Local and global crosstalk among heterochromatin marks drives epigenome patterning in Arabidopsis

Transposable elements (TEs) are robustly silenced by targeting of multiple epigenetic marks, but dynamics of crosstalk among these marks remains enigmatic. In Arabidopsis, TEs are silenced by cytosine methylation in both CpG and non-CpG contexts (mCG and mCH) and histone H3 lysine 9 methylation (H3K9me). While mCH and H3K9me are mutually dependent for their maintenance, mCG and mCH/H3K9me are independently maintained. Here we show that establishment, rather than maintenance, of mCH depends on mCG, accounting for the synergistic colocalization of these silent marks in TEs. When mCG is lost, establishment of mCH is abolished in TEs. mCG also guides mCH in active genes, although genic mCH/H3K9me is removed there. Unexpectedly, the targeting efficiency of mCH depends on relative, rather than absolute, levels of mCG, suggesting underlying global negative controls. We propose that the local positive feedback in heterochromatin dynamics, together with global negative feedback, drive robust and balanced epigenome patterning.

Oral colon-targeting core–shell microparticles loading curcumin for enhanced ulcerative colitis alleviating efficacy

Background The oral colon-targeting drug delivery vehicle is vital for the efficient application of curcumin (Cur) in ulcerative colitis (UC) treatment because of its lipophilicity and instability in the gastrointestinal tract. Methods The core–shell microparticle (MP) system composed of eco-friendly materials, zein and shellac, was fabricated using a coaxial electrospray technique. In this manner, Cur was loaded in the zein core, with shellac shell coating on it. The colon-targeting efficiency and accumulation capacity of shellac@Cur/zein MPs were evaluated using a fluorescence imaging test. The treatment effects of free Cur, Cur/zein MPs, and shellac@Cur/zein MPs in acute experimental colitis were compared. Results With the process parameters optimized, shellac@Cur/zein MPs were facilely fabricated with a stable cone-jet mode, exhibiting standard spherical shape, uniform size distribution (2.84 ± 0.15 µm), and high encapsulation efficiency (95.97% ± 3.51%). Particularly, with the protection of shellac@zein MPs, Cur exhibited sustained drug release in the simulated gastrointestinal tract. Additionally, the in vivo fluorescence imaging test indicated that the cargo loaded in shellac@zein MPs improves the colon-targeting efficiency and accumulation capacity at the colonitis site. More importantly, compared with either free Cur or Cur/zein MPs, the continuous oral administration of shellac@Cur/zein MPs for a week could efficiently inhibit inflammation in acute experimental colitis. Conclusion The shellac@Cur/zein MPs would act as an effective oral drug delivery system for UC management.

Design and Optimization of the Circulatory Cell-Driven Drug Delivery Platform

Achievement of high targeting efficiency for a drug delivery system remains a challenge of tumor diagnoses and nonsurgery therapies. Although nanoparticle-based drug delivery systems have made great progress in extending circulation time, improving durability, and controlling drug release, the targeting efficiency remains low. And the development is limited to reducing side effects since overall survival rates are mostly unchanged. Therefore, great efforts have been made to explore cell-driven drug delivery systems in the tumor area. Cells, particularly those in the blood circulatory system, meet most of the demands that the nanoparticle-based delivery systems do not. These cells possess extended circulation times and innate chemomigration ability and can activate an immune response that exerts therapeutic effects. However, new challenges have emerged, such as payloads, cell function change, cargo leakage, and in situ release. Generally, employing cells from the blood circulatory system as cargo carriers has achieved great benefits and paved the way for tumor diagnosis and therapy. This review specifically covers (a) the properties of red blood cells, monocytes, macrophages, neutrophils, natural killer cells, T lymphocytes, and mesenchymal stem cells; (b) the loading strategies to balance cargo amounts and cell function balance; (c) the cascade strategies to improve cell-driven targeting delivery efficiency; and (d) the features and applications of cell membranes, artificial cells, and extracellular vesicles in cancer treatment.

Photodynamic Therapy—An Up-to-Date Review

The healing power of light has attracted interest for thousands of years. Scientific discoveries and technological advancements in the field have eventually led to the emergence of photodynamic therapy, which soon became a promising approach in treating a broad range of diseases. Based on the interaction between light, molecular oxygen, and various photosensitizers, photodynamic therapy represents a non-invasive, non-toxic, repeatable procedure for tumor treatment, wound healing, and pathogens inactivation. However, classic photosensitizing compounds impose limitations on their clinical applications. Aiming to overcome these drawbacks, nanotechnology came as a solution for improving targeting efficiency, release control, and solubility of traditional photosensitizers. This paper proposes a comprehensive path, starting with the photodynamic therapy mechanism, evolution over the years, integration of nanotechnology, and ending with a detailed review of the most important applications of this therapeutic approach.

Evaluating the Targeting Efficiency of Anti-EGFR Functionalised Nanoparticles to Head and Neck Cancer Cells for Use in NIR-II Optical Window

Gold nanoparticles have been indicated for use in a diagnostic and/or therapeutic role in several cancer types. The use of gold nanorods (AuNRs) with a surface plasmon resonance (SPR) in the second Near-Infrared II (NIR-II) optical window promises deeper anatomical penetration through increased maximum permissible exposure and lower optical attenuation. In this study, the targeting efficiency of anti-epidermal growth factor receptor (EGFR) antibody functionalised AuNRs with an SPR at 1064 nm was evaluated in vitro. Four cell lines, KYSE-30, CAL-27, Hep-G2 and MCF-7 that either over or under expressed EGFR were used. This expression was confirmed by flow cytometry and immunofluorescence. Cytotoxicity assays showed no AuNRs toxicity to both EGFR positive and EGFR negative cell lines up to a concentrations of 19 µg/ml. Optical microscopy demonstrated a significant difference (p<0.0001) between targeted AuNRs (tAuNRs) and untargeted AuNRs (uAuNRs) in all four cancer cell lines. This study demonstrates that anti-EGFR functionalisation significantly increased the number of tAuNRs associated with each EGFR positive cancer cell. This successful targeting highlights the use of tAuNRs for molecular photoacoustic imaging or tumour treatment through plasmonic photothermal therapy.