# Structure-Selective Polydopamine Coating on Drug Nanoparticles

## TL;DR

This study shows that polydopamine coatings on drug nanoparticles behave selectively based on drug structure, improving stability and effectiveness.

## Contribution

The discovery of structure-dependent PDA coating behavior and a predictive model for coating selectivity.

## Key findings

- PDA coating selectivity correlates with nitrogen content and N–C–N motifs in drug molecules.
- PDA coating improves colloidal stability and drug efficacy in HCT116 xenograft models.
- A predictive decision tree model correctly classifies 80% of compounds based on molecular descriptors.

## Abstract

Polydopamine (PDA) is widely regarded as a universal
coating material
with substrate-independent adhesion. Here we report the first demonstration
of selective PDA coating on small molecule drugs, revealing unexpected
structure-dependent behavior that challenges this paradigm. Systematic
screening of 30 chemotherapeutic agents in IR783-stabilized nanoparticles
(>90% drug loading) showed dramatic coating variations governed
by
molecular structure rather than conventional hydrophobic or π–π
interactions. Using Dragon molecular descriptors and principal component
analysis, we developed a predictive decision tree model based on nitrogen
content and bonding topology that correctly classified 80% of validation
compounds. Coating selectivity correlates primarily with nitrogen
percentage and N–C–N motifs, fundamentally expanding
the understanding of PDA surface chemistry beyond nonselective adhesion
mechanisms. Representative drugs (trametinib, dasatinib) demonstrated
that PDA coating significantly improves colloidal stability and reduces
aggregation without compromising drug loading or release kinetics. In vivo evaluation in HCT116 xenografts confirmed superior
efficacy over free drug with improved formulation stability. These
findings establish PDA coating selectivity as a previously unrecognized
material phenomenon and provide computational tools for rational nanoparticle
surface design.