Meihua Yu

Anti‐inflammatory colchicine therapy has emerged as a new era for atherosclerotic cardiovascular diseases. However, the therapeutic benefit of colchicine has not been clearly defined. Herein, we present a double coordination‐driven approach to fabricate a stable metal‐organic nano‐assembly of colchicine (COL‐TA‐Zn) by uniting the tropolone ring of colchicine (COL), phenolic groups of tannic acid (TA), and Zn ²⁺ ions. This design leverages the antioxidant and anti‐inflammatory properties of COL and TA to create a nanoscale platform capable of scavenging radicals and modulating inflammatory pathways. Through robust Zn ²⁺ coordination, the resulting COL‐TA‐Zn nanocomplexes exhibit enhanced stability under physiological conditions, ensuring efficient delivery and sustained bioactivity. In vitro assays confirm suppression of foam cell formation and multiple inflammatory mediators, suggesting significant potential for managing atherosclerosis by targeting both oxidative stress and inflammation. Intravenous administration of COL‐TA‐Zn in Apoe ^{− / −} mice significantly reduces atherosclerotic plaque area, MMP‐9, TNF‐α, and reactive oxygen species (ROS) levels, thereby illustrating its superior anti‐atherosclerotic efficacy compared to COL alone. These findings highlight the promise of the dual coordination‐driven nanoplatform in cardiovascular disease treatment.

Anti‐inflammatory colchicine therapy has emerged as a new era for atherosclerotic cardiovascular diseases. However, the therapeutic benefit of colchicine has not been clearly defined. Herein, we present a double coordination‐driven approach to fabricate a stable metal‐organic nano‐assembly of colchicine (COL‐TA‐Zn) by uniting the tropolone ring of colchicine (COL), phenolic groups of tannic acid (TA), and Zn ²⁺ ions. This design leverages the antioxidant and anti‐inflammatory properties of COL and TA to create a nanoscale platform capable of scavenging radicals and modulating inflammatory pathways. Through robust Zn ²⁺ coordination, the resulting COL‐TA‐Zn nanocomplexes exhibit enhanced stability under physiological conditions, ensuring efficient delivery and sustained bioactivity. In vitro assays confirm suppression of foam cell formation and multiple inflammatory mediators, suggesting significant potential for managing atherosclerosis by targeting both oxidative stress and inflammation. Intravenous administration of COL‐TA‐Zn in Apoe ^{− / −} mice significantly reduces atherosclerotic plaque area, MMP‐9, TNF‐α, and reactive oxygen species (ROS) levels, thereby illustrating its superior anti‐atherosclerotic efficacy compared to COL alone. These findings highlight the promise of the dual coordination‐driven nanoplatform in cardiovascular disease treatment.

This review discusses design strategies for external stimuli-driven hydrogels with in situ catalytic processes. It highlights precise control over the properties, elucidating regulatory mechanisms and deepening the understanding of the applications.

Cancer immunotherapies rely on CD8 ⁺ cytolytic T lymphocytes (CTLs) in recognition and eradication of tumor cells via antigens presented on major histocompatibility complex class I (MHC-I) molecules. However, we observe MHC-I deficiency in human and murine urologic tumors, posing daunting challenges for successful immunotherapy. We herein report an unprecedented nanosonosensitizer of one-dimensional bamboo-like multisegmented manganese dioxide@manganese–bismuth vanadate (BMMBV) to boost multiple branches of immune responses targeting MHC-I–deficient tumors. BMMBV markedly augments sonodynamic activity contributed by manganese heteroatoms in the lattice of bismuth vanadate with narrowing bandgaps. Under sonoirradiation, BMMBV enhances tumor antigen spreading and emission of adjuvant signals, which potentiate dendritic cell maturation, thereby eliciting high aptitude of CTLs. This therapy substantially up-regulates MHC expression on tumor cells, which are reversely sensitive to CTLs. Alongside, extensive innate immune cells complement the cytolytic activity of CTLs for eliminating mouse urologic tumors. This study offers a reinforced strategy against antigen-loss immune-evasive tumor.

Therapeutic DNA cancer vaccines can stimulate specific immune responses against cancer antigens but often induce suboptimal therapeutic responses. Here, we demonstrate that a manganese-doped silica nanoparticle STING agonist (MSNA) enhances the immune response of plasmid DNA vaccines, promoting the activation and migration of distinct subsets of dendritic cell (DC) and improving antitumor immunity in three animal models. MSNA coadministered with an alpha-fetoprotein (AFP) encoded plasmid DNA (AFP-DNA) elicited significantly higher AFP-specific CD8 T cell responses than free AFP-DNA. Animals immunized with MSNA-AFP-DNA remained tumor-free in an AFP expressing hepatocellular carcinoma challenge model. MSNA combined with a DNA plasmid encoding the human papillomavirus type 16 oncoproteins E6 and E7 induced potent E7-specific CD8 T cell responses, preventing the growth of E7-expressing solid TC-1 tumors and promoting the shrinkage of E7-expressing skin grafts. These findings together demonstrate that coadministration of MSNA can improve the efficacy of therapeutic DNA vaccines targeting cancer-specific antigens.

The therapeutic efficacy of vaccines for treating cancers in clinics remains limited. Here, a rationally designed cancer vaccine by placing immunogenically differential and clinically approved aluminum (Al) or manganese (Mn) in a 2D nanosheet (NS) architecture together with antigens is reported. Structurally optimal NS with a high molar ratio of Mn to Al (MANS‐H) features distinctive immune modulation, markedly promoting the influx of heterogeneous innate immune cells at the injection site. Stimulation of multiple subsets of dendritic cells (DCs) significantly increases the levels, subtypes, and functionalities of antigen‐specific T cells. MANS‐H demonstrates even greater effectiveness in the production of antigen‐specific antibodies than the commercial adjuvant (Alhydrogel) by priming T helper (Th)2 cells rather than T follicular helper (Tfh) cells. Beyond humoral immunity, MANS‐H evokes high frequencies of antigen‐specific Th1 and CD8⁺ cell immunity, which are comparable with Quil‐A that is widely used in veterinary vaccines. Immunized mice with MANS‐H adjuvanted vaccines exert strong potency in tumor regression by promoting effector T cells infiltrating at tumor and overcoming tumor resistance in multiple highly aggressive tumor models. The engineered immunogen with an intriguing NS architecture and safe immunopotentiators offers the next clinical advance in cancer immunotherapy.

Despite the proceeds in the management of acute myocardial infarction (AMI), the current therapeutic landscape still suffers from limited success in the clinic. Exaggerated inflammatory immune response and excessive oxidative stress are key pathological features aggravating myocardium damage. Herein, catalytic immunomodulatory nanocomplexes as anti‐AMI therapeutics to resolve reactive oxygen species (ROS)‐proinflammatory neutrophils‐specific‐inflammation is engineered. The nanocomplexes contain lyophilic S100A8/9 inhibitor ABR2575 in the core of nanoemulsions, which effectively disrupts the neutrophils‐S100A8/A9‐inflammation signaling pathway in the AMI microenvironment. Additionally, ROS scavenger ultrasmall Cu _x O nanoparticles are incorporated into the nanoemulsions via coordinating with SH groups of poly(ethylene glycol) (PEG)‐conjugated lipids, which mimic multiple enzymes, dramatically alleviating the oxidative stress damage to myocardial tissue. This combination strategy significantly suppresses the infiltration of pro‐inflammatory monocytes, macrophages, and neutrophils, as well as the secretion of inflammatory cytokines. Additionally, it potentially triggers cardiac Tert activation, which promotes myocardial function and decreases infarction size in preclinical murine AMI models. This approach offers a new nanomedicine for treating AMI, resulting in a dramatically enhanced therapeutic outcome.