Impact of inner hydrophobicity of dendrimer nanomicelles on biodistribution: a PET imaging study

Self-assembly is a powerful strategy for building nanosystems for biomedical applications. We have recently developed small amphiphilic dendrimers capable of self-assembling into nanomicelles for tumor imaging. In this context, we studied the impact of increased hydrophobicity of the amphiphilic dendrimer on hydrophilic/hydrophobic balance and consequently on the self-assembly and subsequent biodistribution. Remarkably, despite maintaining the exact same surface chemistry, similar zeta potential, and small size, the altered and enlarged hydrophobic component within the amphiphilic dendrimer led to enhanced stability of the self-assembled nanomicelles, with prolonged circulation time and massive accumulation in the liver. This study reveals that even structural alteration within the interior of nanomicelles can dramatically impact biodistribution profiles. This finding highlights the deeper complexity of rational design for nanomedicine and the need to consider factors other than surface charge and chemistry, as well as size, all of which significantly impact the biodistribution of self-assembling nanosystems.