ICEFAB-Nano: An Integrated Computational-Experimental Framework to Accelerate the Development of Highly Biofunctional Nanotherapeutics for Healthy and Cancerous Applications

Overview

The rational design of biofunctional nanomaterial (NM) -therapeutics is hindered by limited predictive tools, particularly regarding microenvironment -modulated release, in vitro /in vivo cytotoxicity in both cancerous and healthy cells, and biodistribution across organs and tumors. To address these challenges, ICEFAB-Nano emerges as first-in-class in silico platform built upon the largest NM -Quantitative Structure Activity Relationship (QSAR) datasets for seven targeted functions, yielding >14,000 previously unextracted datapoints. Each in vitro QSAR dataset incorporates 27 descriptors spanning macro -scale (size, shape, zeta potential, etc.) and molecular-scale features extracted via RDKit. Descriptors trained numerous off -the-shelf and custom Machine Learning models, while regression models were integrated with Physiologically Based Pharmacokinetic Modeling for in vivo predictions. A SHapley Additive exPlanations (SHAP)-based iterative reduction pipeline was employed to rank features and identify those most critical. The best -performing models for each function were subsequently integrated to create ICEFAB-Nano, which demonstrated robust validation on both internal and externally curated test sets. Furthermore, ICEFAB-Nano mined an experimental library of >600 known NM formulations originally designed for diverse applications to pinpoint NMs optimized for specific therapeutic goals. For validation, it selected Silica NMs for doxorubicin and paclitaxel chemotherapeutic delivery to ovarian cancer cells and Lipid NMs for GFP siRNA nucleic acid delivery to healthy kidney cells. Eleven candidates, chosen via Cluster Analysis, exhibited strong in vitro performance. ICEFAB -Nano’s SHAP explainability pipeline yielded translatable, t estable hypotheses, including a first -case finding that charge dispersion in highly positive NM surface coatings can shield healthy cells from toxicity while preserving NM functionality. Tennessee

Competition history

• JSHS 2025 Category not listed

Resources

• National JSHS abstract book ↗

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