Polydopamine-coated ferric oxide nanoparticles for R848 delivery for photothermal immunotherapy in breast cancer.

Breast cancer, which requires comprehensive multifunctional treatment strategies, is a major threat to the health of women. To develop multifunctional treatment strategies, we combined photothermal therapy (PTT) with immunotherapy in multifunctional nanoparticles for enhancing the anti-tumor efficacy. Fe3O4 nanoparticles coated with the polydopamine shell modified with polyethylene glycol and cyclic arginine-glycyl-aspartic peptide/anisamide (tNP) for loading the immune adjuvant resiquimod (R848) (R848@tNP) were developed in this research. R848@tNP had a round-like morphology with a mean diameter of 174.7 ± 3.8 nm, the zeta potential of -20.9 ± 0.9 mV, the drug loading rate of 9.2 ± 1.1 %, the encapsulation efficiency of 81.7 ± 3.2 %, high photothermal conversion efficiency and excellent magnetic properties in vitro. Furthermore, this research also explored the anticancer efficacy of nanoparticles against the breast cancer under the near-infrared (NIR) light (808 nm) in vitro and in vivo. R848@tNP-based NIR therapy effectively inhibited the proliferation of breast cancer cells. Moreover, R848@tNP mediated PTT significantly enhanced the maturation of dendritic cells in vitro. Additionally, R848@tNP enhances the anti-tumor effect and evoked an immune response under NIR in vivo. Furthermore, the biosafety of R848@tNP was fully investigated in this study. Collectively, these results clearly demonstrate that R848@tNP, with magnetic resonance imaging characteristics, is a potential therapeutic for breast cancer that combines PTT with the immunotherapy.

XA pH-Responsive and Colitis-Targeted Nanoparticle Loaded with Shikonin for the Oral Treatment of Inflammatory Bowel Disease in Mice.

Epidemiology shows that more than 6.8 million people in the world are influenced by inflammatory bowel disease (IBD) each year. IBD is a refractory inflammatory disease, and the disease mainly affects the colon. Shikonin (SK) was originally extracted from traditional Chinese medicine "Zicao" (with an English name Lithospermum erythrorhizon) and found to inhibit inflammation, regulate immunity, and be involved in healing wounds. Herein, we used chitosan (CS), hyaluronic acid (HA), and pH-responsive polymer Eudragits S100 (ES100) to design SK-loaded ES100/HA/CS nanoparticles (SK@SAC) as an oral delivery system to treat the colitis mice. Particle size of SK@SAC was 190.3 nm and drug loading efficiency was 6.6%. SAC nanoparticles accumulated in RAW264.7 macrophages and exhibited colitis-targeted ability by increasing the local drug concentration as well as reducing nonspecific distribution after oral gavage. In TNBS-induced IBD mice, SK@SAC treatment had significant therapeutic effects, regulated of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1ß) and anti-inflammatory cytokines (IL-10 and TGF-ß), and also inhibited COX-2 and iNOS activity. SK@SAC also increased tight junction protein ZO-1 and occludin to some extent. These promising results showed that this novel oral SK-loaded nanoparticle drug delivery system for targeted treatment provides a new strategy for the management of IBD.

A genome-wide positioning systems network algorithm for in silico drug repurposing.

Recent advances in DNA/RNA sequencing have made it possible to identify new targets rapidly and to repurpose approved drugs for treating heterogeneous diseases by the 'precise' targeting of individualized disease modules. In this study, we develop a Genome-wide Positioning Systems network (GPSnet) algorithm for drug repurposing by specifically targeting disease modules derived from individual patient's DNA and RNA sequencing profiles mapped to the human protein-protein interactome network. We investigate whole-exome sequencing and transcriptome profiles from ~5,000 patients across 15 cancer types from The Cancer Genome Atlas. We show that GPSnet-predicted disease modules can predict drug responses and prioritize new indications for 140 approved drugs. Importantly, we experimentally validate that an approved cardiac arrhythmia and heart failure drug, ouabain, shows potential antitumor activities in lung adenocarcinoma by uniquely targeting a HIF1α/LEO1-mediated cell metabolism pathway. In summary, GPSnet offers a network-based, in silico drug repurposing framework for more efficacious therapeutic selections.