Design and Synthesis of Novel Amphiphilic Polymers for MRI and Selective Targeting in Cancer Diagnosis /Therapy

摘要

The primary challenge in chemotherapy of cancer is the absence of selectivity of medicines/drugs that can target fast growing malignant cells. As a result side effects limit its application or prevent its use altogether. To enhance the efficacy of chemotherapy it is pertinent to develop a methodology which can target only malignant cells. To address this problem a carrier molecule has been designed that can selectively bind with the malignant cells and may deliver the drugs at its specific site of action. Amphiphilic polymers have been synthesized via Lipase (Novozyme-435) catalyzed polymerization of dimethyl 5- hydroxy-isophthalate, dimethyl 5-amino-isophthalate and poly (ethylene glycol) . To provide selectivity for binding a peptide was attached to this polymer through a hydrophilic linker (triethylene glycol) after activating its end group hydroxyl in the form of activated ester-2. Subsequently fluorescent dyes, perfluorocarbons (for 19FMR imaging), and a hydrophobic side chain were attached via simple chemical modifications. This polymer self-assembles into nanoparticles (figure-1) which have potential for in vivo imaging and drug delivery applications in cancer therapy (figure-2). Doxorubicin, a chemotherapeutic drug has been encapsulated into these nano micelles and tested as a "proof of concept" and FITC was attached for visualization via confocal microscopy.