Yihui Deng

Cataract remains the most prevalent cause of visual impairment and irreversible blindness worldwide. It is characterized by lens opacification arising from

Atherosclerotic cardiovascular disease (ASCVD) poses a severe threat to human health, and the global prevalence of atherosclerosis-related diseases continues to rise, necessitating urgent exploration of novel strategies. Inspired by the close links between tumors and atherosclerosis (AS), as well as the clinical reality of their comorbidity, the present study encapsulated pitavastatin within liposomes and modified them with sialic acid-cholesterol (SA-CH) to achieve targeted drug delivery via peripheral blood neutrophils (PBNs). Compared to oral pitavastatin administration, sialic acid-modified pitavastatin liposomes (PIT-SAL) demonstrated superior efficacy in attenuating disease progression in atherosclerotic mice, with sustained therapeutic effects even after treatment cessation, suggesting the potential for eradication of AS. Notably, PIT-SAL additionally exhibited antitumor potential by effectively reducing tumoral cholesterol accumulation while enhancing T-cell infiltration. Collectively, our preliminary findings highlight the great translational potential of PIT-SAL as a targeted therapy for both AS and tumors, offering a potential breakthrough in managing these interconnected diseases.

Epigenetic homeostasis is integral to the development of malignant tumors. Combining epigenetic drugs with chemotherapy is a promising strategy to overcome the challenges in treating lung metastasis from melanoma. In this study, we constructed sialic acid-modified ibrutinib-phospholipid complex nanoparticles (SA-IBR-NPs) to actively target and deliver the drug to lung metastasis sites through the mononuclear phagocytic system (MPS) pathway. A highly soluble 5-Carboxy-8-hydroxyquinoline-arginine salt (IOX1-Arg) was also developed to inhibit tumor cells' intrinsic immune escape mechanisms. The combined administration of IOX1-Arg and SA-IBR-NPs significantly reduced the migration and invasion abilities of B16F10 cells and inhibited lung metastasis. The number of tumor nodules in experimental groups (including single-agent treatment groups, non-SA-modified nanoparticle groups, and non-IOX1-Arg combined groups) was 3.67-28.00 times higher than that of the IOX1-Arg + SA-IBR-NPs. The malignant index of tumor metastasis in single therapy or plain nanoparticle groups was 5.38-1062.29 times higher than that of the IOX1-Arg + SA-IBR-NP treatments, as well. This combination therapy also increased the levels of cytotoxic T cells. The antitumor immune response was effectively restructured by blocking the intrinsic escape mechanism of tumor cells and simultaneously inhibiting the immunosuppressive factors in the microenvironment. This strategy presents a novel approach to enhancing targeted therapy for metastatic tumors.

The prevalence of anti-polyethylene glycol (PEG) antibodies poses a significant challenge for the clinical translation of PEGylated liposomes, leading to an accelerated blood clearance (ABC) phenomenon and diminishing therapeutic effectiveness.

Inflammation-related immune cell subsets with abnormal activation, impaired tolerance, and complex intercellular interactions drive the progression and incurability of autoimmune diseases (AIDs). Here, we present an antigen-free nanovaccine-enabled holo-immunotherapy that comprehensively modulates inflammation, innate immunity, and adaptive immunity. The nanovaccine, composed of dual NF-κB inhibitors (budesonide and bortezomib) and comodified with sialic acid (SA) and enzyme-cleavable polyethylene glycol (PEG), leverages the SA-Siglec axis for targeted delivery to inflammation-related macrophage, dendritic cell, and CD4⁺ T cell subsets. By bridging innate and adaptive immunity, this multitargeted strategy synergistically reshapes the inflammatory microenvironment, establishes robust memory immune tolerance, and promotes immune homeostasis restoration, leading to sustained efficacy and delayed relapse in the collagen-induced arthritis (CIA) mouse model. Unlike traditional vaccines, the antigen-free design eliminates reliance on exogenous antigens, minimizes off-target immune risks, and holds promise for broader clinical applicability. The nanovaccine outperforms anti-TNF-α antibodies in treating models of CIA, adjuvant-induced arthritis, and chronic ulcerative colitis, highlighting its potential as a universal vaccine platform for AID therapy. Overall, this work provides a strategy to address AID challenges through precise immune regulation and durable therapeutic benefits.

Neutrophils play a critical role in the cancer-immunity cycle and are associated with poor clinical outcomes. Recent research has primarily focused on the targeted delivery, phenotypic reversal, and reprogramming of tumor-associated neutrophils, while the impact of disease-associated neutrophils (DANs) on antitumor therapy remains understudied. Since liposomes, as drug delivery carriers, possess excellent biocompatibility and stability, making them particularly suitable for combination therapy, we optimized the formulation of asymmetrically branched polyethylene glycol-modified mitomycin C lipid prodrug liposomes (PEG2,5 K@MLP-L) and prepared hyaluronic acid and sialic acid ester stearate-co-modified dexamethasone palmitate liposomes (HA*SAS@DXP-L) to study DANs in normal, obese, aged, and septic mice. An increase in mitochondria and lysosomes in Ly-6G+CXCR2high DANs accelerated drug clearance, reduced CD3+CD8+ T cell activity in tumor-draining lymph nodes, and decreased CD8+ T cell infiltration in tumors. As the proportion of DANs increased, the efficacy of PEG2,5 K@MLP-L decreased. Combination therapy with PEG2,5 K@MLP-L and HA*SAS@DXP-L can reshape DANs, promote the cancer-immunity cycle, and enhance treatment efficacy. This study identifies key characteristics and functions of DANs and presents a promising strategy for improving clinical outcomes.