Gadolinium(III) Coordinated Theranostic Polymer for Proficient Sequential Targeting-Combinational Chemotherapy and T-1 Weighted Magnetic Resonance Imaging

The combination therapy where a single delivery agent codelivers multiple drugs at the targeted site has become a promising strategy to achieve synergistic chemotherapeutic effect leading to the suppression of cancer cell drug resistance capability. Herein, we developed a theranostic polymer CP PG MT Gd that can sequentially target folate receptors (FR) onto cancer cell apical membrane at an early phase and exhibited late phase combinational chemotherapy through topoisomerase-I (TOPO-I) and dihydrofolate reductase (DHFR) inhibition synergistically, which resulted in inhibition of nucleic acid biosynthesis. This dual-acting self-targeted CP PG MT Gd polymer could effectively track the loaded chemotherapeutic agents (camptothecin-methotrexate) through MRI-tomography and eventually played a decisive role for subsequent dose-determination in real-time.A thorough comparative investigation on FR-targeting competence of CP PG MT Gd was executed with a folic acid (FOL) conjugated CP PG FL Gd (targeted system) and a nontargeted CP PG Gd polymers using human cervical cancer, HeLa (high FR-expression), and breast cancer MCF-7 (low FR-expression) cell lines. The incorporated Gd(III) chelate-complex in the CP PG MT Gd theranostic polymer displayed remarkable T-1 weighted MRI-proficiency with longitudinal specific relaxivity constant, r(1) = 21.85 mM(-1) S-1. Therefore, the MRI-tracking proficiency and sequential targeting-chemotherapy switchable CP PG MT Gd theranostic system opened the way for precise multidrug codelivery at cancer site that might have attractive potential for diagnosis and decisive dose-determination in clinical implication.