Self-Assembly of Modular Bis-MPA Dendrons into Colloidal Particles with Tunable Morphology and Selective Cytotoxicity

Precise control over the physicochemical and biological properties of colloidal particles is essential for the rational design of functional soft materials. In this work, we report a simple and scalable strategy for generating modular dendron particles (MDPs) through the self-assembly of fully characterized small-molecule Bis-MPA dendrons that act as programmable molecular building blocks for colloidal particle formation. By systematically varying three structural domains—the inner functionality, methylene spacer length, and outer connector—we achieve tunable formation of MDPs ranging from nano- to microscale dimensions. Upon solvent evaporation under mild drying conditions, pre-assembled MDPs act as structure-directing seeds that guide the emergence of hierarchical surface morphologies with spiky, scaly, or spherical protrusions, depending on dendron architecture. Importantly, these assemblies exhibit good biocompatibility toward non-tumoral bronchial epithelial (NL-20) cells while displaying selective cytotoxicity toward Neuro-2a neuroblastoma cells, demonstrating that dendron molecular architecture alone can govern particle size, morphology, and biological response without external drug loading. Collectively, these findings highlight modular Bis-MPA dendrons as versatile building blocks for directing particle size, morphology, and biological response through controlled self-assembly and evaporation-driven structuring.