Magnetic Norbornene Polymer as Multiresponsive Nanocarrier for Site Specific Cancer Therapy

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• 作者：Vijayakameswara Rao N ; Mutyala Naidu Ganivada ; Santu Sarkar ; Himadri Dinda ; Koushik Chatterjee ; Tanmoy Dalui ; Jayasri Das Sarma ; Raja Shunmugam
• 刊名：Bioconjugate Chemistry
• 出版年：2014
• 出版时间：February 19, 2014
• 年：2014
• 卷：25
• 期：2
• 页码：276-285
• 全文大小：861K
• ISSN：1520-4812

文摘

A site-specific, stimuli-responsive nanocarrier has been synthesized by conjugating folate, magnetic particles and doxorubicin to the backbone of norbornene polymer. Monomers, namely, cis-5-norbornene-6-(diethoxyphosphoryl)hexanote (mono 1), norbornene grafted poly(ethyleneglycol)-folate (mono 2), and norbornene derived doxorubicin (mono 3) are carefully designed to demonstrate the smart nanorcarrier capabilities. The synthesis and complete characterization of all three monomers are elaborately discussed. Their copolymerization is done by controlled/living ring-opening metathesis polymerization (ROMP) to get the triblock copolymer PHOS-FOL-DOX. NMR spectroscopy and gel permeation chromatography confirm the formation of the triblock copolymer, while FT-IR spectroscopy, thermogravimetric analysis, along with transmission electron microscope confirm the anchoring of iron particle (Fe₃O₄) to the PHOS-FOL-DOX. Drug release profile shows the importance of having the hydrazone linker that helps to release the drug exactly at the mild acidic conditions resembling the pH of the cancerous cells. The newly designed nanocarrier shows greater internalization (about 8 times) due to magnetic field. Also, increased intracellular DOX release is observed due to the folate receptor. From these results, it is clear that PHOS-FOL-DOX has the potential to act as a smart nanoreservoir with the magnetic field guidance, folate receptor targeting, and finally pH stimulation.