Unique Random-Block Polymer Architecture for Site-Specific Mitochondrial Sequestration-Aided Effective Chemotherapeutic Delivery and Enhanced Fluorocarbon Segmental Mobility-Facilitated 19F Magnetic Resonance Imaging

The elevation of the chemotherapeutic efficacy and attenuation of its side effects on healthy cells and tissues become one of the prime targets for the treatment of cancer. Toward this direction, a sequential receptor and mitochondria dual-targeting strategy was implemented in the DX TP PG BN19F theranostic polymer that was anchored with the chemotherapeutic agent doxorubicin, receptor-targeting biotin, and mitochondria-targeting triphenylphosphonium cations. The polymer was flourished with a unique 19F magnetic resonance imaging (MRI) tracer that exhibited high segmental mobility and eventually led to prolonged T2 relaxation time. Furthermore, for the sake of amphiphilicity, the DX TP PG BN19F polymer spontaneously aggregated into nano-sphere with positive zeta potential, where the MRI tracer and biotin embedded at the exterior and displayed site-specific targeting and remarkable 19F MRI capability simultaneously. The mitochondria-targeting competency of the DX TP PG BN19F theranostic polymer was investigated by comparing the non-mitochondrial-targeting DX PG BN19F polymer using fluorescence microscopic cell imaging in human cervical, HeLa, and breast MCF-7 carcinoma cell lines. Moreover, cytotoxicity experiments of the aforementioned theranostic polymers clarified the enhancement of the chemotherapeutic efficacy of DX TP PG BN19F theranostic polymers through effective and precise mitochondrial doxorubicin delivery that forced to follow the apoptotic path.