Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.64898/2026.10.31.763372

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

Liu, N.·Zhu, Q.·Lu, Z.-R.
View original source ↗Export metadata ↓

Abstract

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.

Explore related subjects

bioengineeringPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Liu, N., Zhu, Q., Lu, Z.-R.. 2026-11-03. A cytotoxicity dataset for data-driven design of ionizable lipid nanoparticles. https://doi.org/10.64898/2026.10.31.763372

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

N-GLYcanyzer monitoring of a microperfusion process reveals critical parameters' impact on Trastuzumab biosimilar N-glycoform time evolution

Controlling monoclonal antibody (mAb) N-glycosylation as a critical quality attribute (CQA) remains challenging in continuous and intensified biomanufacturing, where conventional end-point analyses obscure dynamic pathway responses. Here, we deployed the N-GLYcanyzer process analytical technology (PAT) for automated monitoring of a microperfusion process that reveals critical parameters' impact on Trastuzumab biosimilar N-glycoform time evolution across a 20-day culture duration of Chinese Hamster Ovary (CHO) cells in a ~2 mL scale-down microbioreactor perfusion platform. Using offline PAT assays combined with our integrated at-line PAT workflow, we systematically screened six perfusion process parameters: carbon source, viable cell density (VCD), perfusion rate, temperature, and pH. While nutrient limitation and thermal/acidic stress significantly disrupted N-glycans maturation, notably triggering high-mannose (Man5) accumulation and severe productivity penalties under pH 6.7 and 39 {degrees}C operation, targeted feed supplementation with galactose and MnCl2 consistently shifted glycoform profiles away from G0F toward galactosylated species (G1F, G1F', G2F). Crucially, coupling this combined feed strategy with an intensified perfusion rate (1.2 VVD) achieved a sustained, desired galactosylation shift without a productivity cost. These findings demonstrate that nutrient feed composition and perfusion rate are primary levers for steering continuous intensified microperfusion processes for biologics production with desired N-glycoform states and highlight the utility of automated at-line PAT like N-GLYcanyzer for enabling real-time attribute-based control in continuous biomanufacturing.

bioengineering↗
bioRxiv2026

Differential sensing with imprinted and non-imprinted organic electrochemical transistors reduces calibration drift in wearable sweat cortisol sensors

The output of a wearable cortisol sensor drifts over days for reasons unrelated to cortisol, so a calibration made on the first day soon stops being valid. In our differential organic electrochemical transistor, a PEDOT:PSS transistor coated with a molecularly imprinted polymer (MIP) for cortisol is paired with one coated with a non-imprinted polymer (NIP) of the same composition, and the NIP response is subtracted. Over four calibrations in artificial sweat across 14 days, the response of the MIP alone shifted by 15% to 22% of its range on day 1, whereas the differential output shifted by 1% to 10%, and the variation between days at 1 to 10nM fell by 65% to 70% on average for individual pairs. In sweat from one participant, read against the calibration from day 1, both outputs tracked the direction of visible changes in salivary cortisol, while the MIP alone diverged from the differential output, consistent with the laboratory drift.

bioengineering↗
bioRxiv2026

Stop-Flow Lithography Using Hydrodynamic Flow Resistance Regulation and Hydraulic Compliance Minimization for Size-Tunable Anisotropic Multilayered Microparticles Fabrication

Stop-flow lithography (SFL) enables the fabrication of microparticles with designed geometries and material compositions, but its performance relies on rapid flow stopping, which remains particularly challenging in multi-inlet systems with high hydrodynamic flow resistance and hydraulic compliance. Here, we develop a pneumatic-controlled SFL platform with a framework based on flow resistance regulation and hydraulic compliance minimization for fabricating size-tunable anisotropic multilayered microparticles. Our analysis indicates that flow-stopping behavior is governed by the release of extra fluid volume stored in the system due to hydraulic compliance, which arises from the deformation of microfluidic components and the compressibility of the fluid within them. Through numerical modeling and analysis, we identify deformation in the PDMS inlet port region as the dominant contributor to the stored extra fluid volume. By regulating the flow resistance of the tubing relative to that of the outlet channel, the stored extra fluid volume can be preferentially released forward through the outlet or backward through the inlet tubing, enabling rapid flow stopping across configurations with 500, 250, and 100 m outlets. Furthermore, by supporting the PDMS membrane beneath the inlet region with a rigid glass substrate and reducing its dimensions, the hydraulic compliance and consequently the stored extra fluid volume are significantly reduced. With these strategies, microparticles with well-defined boundaries can be fabricated at short, flow-stopping, delay times, and the flow profiles obtained in multi-inlet systems can be preserved during flow stopping and transferred into particle patterns.

bioengineering↗