4.7 Article

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

Journal

ACS APPLIED POLYMER MATERIALS
Volume 4, Issue 3, Pages 1752-1763

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acsapm.1c01591

Keywords

combination therapy; synergistic effect; dihydrofolate reductase; topoisomerase-I; theranostic agent; folate receptor; magnetic resonance imaging

Funding

  1. IISER Kolkata
  2. INSPIRE, New Delhi
  3. DST
  4. Annual Research Fund (ARF) from Indian Institute of Science Education and Research Kolkata

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A theranostic polymer capable of sequentially targeting folate receptors on cancer cells and inhibiting cancer cell growth through multiple mechanisms has been developed. The polymer can track the release of chemotherapeutic drugs through MRI and has the potential for precise multidrug codelivery in clinical applications.
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.

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