Immunomodulatory microneedle patch for enhanced Ferroptosis and immunogenic cell death in postoperative tumor therapy.

Microneedle technologies have emerged as a promising transdermal drug delivery platform for postoperative tumor therapy. Despite their potential, enhancing intracellular drug delivery to tumor cells and boosting the therapeutic efficiency of microneedles pose significant challenges. Herein, we develop a nanomedicine-loaded microneedle to enhance the induction of ferroptosis and immunogenic cell death for postoperative tumor therapy.

Smart Microneedle Arrays Integrating Cell-Free Therapy and Nanocatalysis to Treat Liver Fibrosis.

Liver fibrosis is a chronic pathological condition lacking specific clinical treatments. Stem cells, with notable potential in regenerative medicine, offer promise in treating liver fibrosis. However, stem cell therapy is hindered by potential immunological rejection, carcinogenesis risk, efficacy variation, and high cost.

A LIGHTFUL nanomedicine overcomes EGFR-mediated drug resistance for enhanced tyrosine-kinase-inhibitor-based hepatocellular carcinoma therapy.

Targeting the activated epidermal growth factor receptor (EGFR) via clustered regularly interspaced short palindromic repeat (CRISPR) technology is appealing to overcome the drug resistance of hepatocellular carcinoma (HCC) towards tyrosine kinase inhibitor (TKI) therapy. However, combining these two distinct drugs using traditional liposomes results in a suboptimal synergistic anti-HCC effect due to the limited CRISPR/Cas9 delivery efficiency caused by lysosomal entrapment after endocytosis. Herein, we developed a liver-targeting gene-hybridizing-TKI fusogenic liposome (LIGHTFUL) that can achieve high CRISPR/Cas9 expression to reverse the EGFR-mediated drug resistance for enhanced TKI-based HCC therapy efficiently.

Anti-phagocytosis-blocking repolarization-resistant membrane-fusogenic liposome (ARMFUL) for adoptive cell immunotherapy.

Equipping multiple functionalities on adoptive effector cells is essential to overcome the complex immunological barriers in solid tumors for superior antitumor efficacy. However, current cell engineering technologies cannot endow these functionalities to cells within a single step because of the different spatial distributions of targets in one cell. Here, we present a core-shell anti-phagocytosis-blocking repolarization-resistant membrane-fusogenic liposome (ARMFUL) to achieve one-step multiplexing cell engineering for multifunctional cell construction.

Structural and componential design: new strategies regulating the behavior of lipid-based nanoparticles .

Lipid-based nanoparticles have made a breakthrough in clinical disease as delivery systems due to their biocompatibility, thermal and long-term stability, high loading ability, simplicity of preparation, inexpensive production costs, and scalable manufacturing production. In particular, during the COVID-19 pandemic, this delivery system served as a vital vaccine component for virus confrontation. To obtain effective drug delivery, lipid-based nanoparticles should reach the desired sites with high efficiency, enter target cells, and release drugs.

Circulating Cell-Free DNAs as a Biomarker and Therapeutic Target for Acetaminophen-Induced Liver Injury.

Acetaminophen (APAP) overdose is a leading cause of drug-induced liver injury and acute liver failure, while the detection, prognosis prediction, and therapy for APAP-induced liver injury (AILI) remain improved. Here, it is determined that the temporal pattern of circulating cell-free DNA (cfDNA) is strongly associated with damage and inflammation parameters in AILI. CfDNA is comparable to alanine aminotransferase (ALT) in predicting mortality and outperformed ALT when combined with ALT in AILI.

Alpha lipoic acid-loaded electrospun fibrous patch films protect heart in acute myocardial infarction mice by inhibiting oxidative stress.

Oxidative stress, characterized by excessive accumulation of reactive oxygen species (ROS), is involved in acute myocardial infarction (AMI)-related pathological processes and vascular reperfusion therapy injury. Alpha lipoic acid (LA) exhibits excellent antioxidant properties, however, its application is limited by inherent characteristics, including rapid clearance and extensive volume distribution. In this study, we hypothesized that scavenging cardiac ROS using adequately delivered LA could promote heart repair.

Membrane-Fusion-Mediated Multiplex Engineering of Tumor Cell Surface Glycans for Enhanced NK Cell Therapy.

Natural killer (NK) cell therapies show potential for tumor treatment but are immunologically resisted by the overexpressed immunosuppressing tumor cell surface glycans. To reverse this glycan-mediated immunosuppression, the surface NK-inhibitory glycan expressions need to be downregulated and NK-activating glycan levels should be elevated synchronously with optimal efficiency. Here, a core-shell membrane-fusogenic liposome (MFL) is designed to simultaneously achieve the physical modification of NK-activating glycans and biological inhibition of immunosuppressing glycans on the tumor cell surface via a membrane-fusion manner.