Hetero-Trifunctional Malonate-Based Nanotheranostic System for Targeted Breast Cancer Therapy

Designing multifunctional linkers is crucial for tricomponent theranostic targeted nanomedicine development as they are essential to enrich polymeric systems with different functional moieties. Herein, we have obtained a hetero-trifunctional linker from malonic acid and demonstrated its implication as an amphiphilic targeted nanotheranostic system (CB DX UN PG FL). We synthesized it with varying hydrophilic segment to fine-tune the hydrophobic/hydrophilic ratio to optimize its self-assembly. pH-responsive hydrazone-linked doxorubicin was conjugated to the backbone (UN PG FL) containing folate as a targeting ligand. Cobalt carbonyl complex was used for T₂-weighted magnetic resonance imaging (MRI). Electron micrographs of optimized molecule CB DX UN PGFL in an aqueous system have demonstrated about 50-60 nm-sized uniform micelles. The relaxivity study and the one-dimensional (1D) imaging experiments clearly revealed the effect of the nanotheranostics system on transverse relaxation (T₂) of water molecules, which validated the system as a T₂-weighted MRI contrast agent. The detailed in vitro biological studies validated the targeted delivery and anticancer potential of CB DX UN PGFL. Combining the data on transverse relaxation, folate mediated uptake, and anticancer activity, the designed molecule will have a significant impact on the development of targeted theranostic.