Biology subjects

Lu, Z.-R.

Publications and source records attributed to Lu, Z.-R..

3 recordsLinked to original sources

bioRxiv2026

A cytotoxicity dataset for data-driven design of ionizable lipid nanoparticles

Ionizable lipid nanoparticles (LNPs) are widely used to deliver nucleic acid therapeutics, but the design of safe LNPs remains challenging due to the complex activity relationships among structure, composition, and physicochemical properties. Here, we present a curated dataset, the Lipid Nanoparticle Cytotoxicity Database (LNPCD), which aggregates 1,413 LNP cytotoxicity measurements across 1,288 unique ionizable lipids drawn from 11 high-throughput combinatorial studies. Lipid structures were generated computationally from the published libraries and manually verified against the original publications. Each record pairs a machine-readable SMILES representation of the ionizable lipid with its measured viability endpoint and the associated experimental descriptors, including cell line, dose, and cargo type. The dataset provides a traceable resource for examining how ionizable lipid structure and experimental conditions relate to in vitro cell viability, and for developing and evaluating computational models of lipid nanoparticle cytotoxicity.

bioengineering↗

bioRxiv2025

Inhibition of KDEL receptors remodels the tumor microenvironment for robust T cell independent tumor regression

Tumor immunotherapy is supported by low-grade inflammatory conditions at the microenvironment, triggered by immunogenic cell death (ICD). However, ICD is dampened when tumors acquire resistance, affecting immune recognition. KDEL receptors (KDELRs), through a retrograde Golgi-to-ER transport, prevent spontaneous secretion of KDEL proteins. We report that inhibition of a single KDELR in a minor fraction of tumor cells, primarily KDELR2, provokes robust infiltration of macrophages and neutrophils into the tumor microenvironment, resulting in a complete regression of both immunogenic and non-immunogenic tumors independently of T cells. Importantly, in the course of regression, anti-tumor T cells are primed, conferring protection against a second challenge. Recapitulated by intratumoral delivery of siDKELR2 utilizing lipid nanoparticles, we implicate KDELR2 as a target to unleash an unusual robust innate immune response, which represents a tractable approach to initiate an adaptive response downstream, bypassing conventional ICD-inducing therapies. We propose KDELR targeting as a strategy to improve immunotherapy across tumor types, including "cold" tumors resistant to T cell-based immunotherapies.

immunology↗

bioRxiv2019

Extradomain-B Fibronectin is a molecular marker of invasive breast cancer cells

Breast tumor heterogeneity is a major impediment to oncotherapy. Tumor cells undergo rapid clonal evolution, thereby acquiring significant growth and invasive advantages. The absence of specific markers of these high-risk tumors precludes efficient therapeutic and diagnostic management of breast cancer. Given the critical function of tumor microenvironment in the oncogenic circuitry, we sought to determine the role of the extracellular matrix oncoprotein, extradomain-B fibronectin (EDB-FN), as a molecular marker of aggressive cancers. High-risk invasive cell lines generated from relatively less invasive MCF7 and MDA-MB-468 breast cancer cells by long-term TGF-{beta} treatment and chemoresistance demonstrated hybrid epithelial-mesenchymal phenotype, enhanced motility, and significantly elevated EDB-FN levels in 2D- and 3D-cultures. To determine if EDB-FN could serve as a therapy-predictive marker, the invasive cell lines were treated with MK2206-HCl, a pan-AKT inhibitor. Phospho-AKT depletion reduced EMT and invasion of the populations, with a concomitant decrease in EDB-FN expression, partly through the phosphoAKT-SRp55 pathway, demonstrating that EDB-FN expression is strongly associated with high-risk breast cancer. EDB-FN is a promising molecular marker for accurate detection, differential diagnosis, and non-invasive therapeutic surveillance of aggressive breast cancer.\n\nSummary StatementDynamic changes in invasive properties of breast cancer cells directly influence extradomain-B fibronectin levels, suggesting its potential role as a molecular marker for active surveillance and therapeutic monitoring of breast cancer.

cancer biology↗