Magnetic Norbornene Polymer as Multiresponsive Nanocarrier for Site Specific Cancer Therapy

Abstract

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.

Recent developments in hyaluronic acid-based nanomedicine for targeted cancer treatment

“…[97,98] However, bare inorganic nanoparticles are highly unstable in physiological conditions and form large aggregates, which are rapidly cleared from the body. Therefore, these nanoparticles are usually coated with natural or synthetic polymers to impart biocompatibility and prolong circulation.…”

“…Therefore, these nanoparticles are usually coated with natural or synthetic polymers to impart biocompatibility and prolong circulation. [98] The targeting ability is achieved by conjugating cell-specific ligands onto the surface of the nanoparticles. Recently, Lee et al prepared HA-immobilized super magnetic iron oxide nanoparticles (HASPION) for tumor-targeted magnetic resonance imaging.…”

Super paramagnetic Norbornene Copolymer Functionalized with Biotin and Doxorubicin: A Potential Unique Site-Specific Theranostic Agent

“…The attachment of magnetic particles helps the drug-carrier system further, as this magnetic particle can be utilized as MR imaging agent. 11 Magnetic as well as drug containing polymersomes have a great potential for both diagnostic and therapeutic applications. Tracking drug carriers by MRI to ensure therapeutic monitoring, provide huge decision making benefits in the nano medicine.…”

“…11,24 But in the most of the example, the noncovalent encapsulation of the magnetic particle is explored. 11 Due to this noncovalent approach leakage of the magnetic particle from the polymeric nanocarrier is observed in most of the systems. So it is necessary to have a water-soluble theranostic agent to maintain the therapeutic as well as magnetic particle concentration over long time period.…”

Fabrication of Size-Tunable Silica Particles During Seed-Growth Process

“…Consequently, Irvine reported that nanoporous silica spheres wrapped around with fluid-phase lipid membranes are promising drug delivery systems for tumor treatment (Irvine, 2011). Although, for more efficient cancer therapy, so-called anticancer drug cocktails are being taken by patients (Vijayakameswara, 2013). Moreover, it turned out that the new particle was an effective cargo-carrying molecular shuttle for mix of doxorubicine and two other potential chemotherapeutics such as previously described cisplatin and 5-fluorouracil (Irvine, 2011).…”