Towards AI-Driven Nanomedicine Discovery: A Benchmark and Multimodal Learning Framework for Nano Self-Assembly Prediction

Abstract

Nano self-assembly organizes molecular components into bioactive nanoscale structures. Self-assembled nanoparticles (NAPs) derived from Chinese herbal formulas and applications such as anti-lung-cancer therapy demonstrate the substantial potential of self-assembly for nanomedicine discovery. Yet discovery still relies on costly wet-lab screening, while existing machine learning approaches lack standardized tasks, effective pairwise compatibility modeling, and public benchmarks with unified evaluation. To address these limitations, we formalize NSA prediction as a binary classification task for predicting self-assembly between molecular pairs and then establish NSA-Bench, the first public benchmark with curated molecular combinations, experimental conditions, self-assembly labels, and standardized evaluation protocols. We further develop NSA-Net, an interaction-aware multimodal framework that integrates complementary molecular evidence from graph topology, sequence semantics, and physicochemical descriptors to learn molecular-pair representations for self-assembly prediction. Extensive experiments on NSA-Bench show that NSA-Net achieves a ROC-AUC of $0.9470\pm0.0112$ (Small) and $0.9492\pm0.0062$ (Large). On the Small track, it surpasses the strongest machine-learning and graph-based baselines by 3.9 and 17.1 percentage points, respectively. Representation analyses reveal interpretable molecular characteristics associated with self-assembly prediction captured by the learned representations. Moreover, an NSA-Agent case study further demonstrates how NSA-Net predictions can support formulation refinement through experimental-condition-aware reasoning. Our code is available at https://github.com/developer-hq/NSA-Net.