Engineering a New Class of Multiarm Homopolymer for Sustainable Drug Delivery.

The first example of simple nanoaggregates, self-assembled from a new class of polymer has been explored. The synthesis and characterization of polyethylene glycol and doxorubicin attached to a 1,6-heptadiyne derivative (Macromonomer) are clearly described. Macromonomer is polymerized via olefin metathesis living cyclopolymerization method using the Grubbs-Hoveyda catalyst to produce a water-soluble Dox-Peg-Rcp-Fmoc polymer. All of the monomers and polymers are carefully characterized by GPC and 1H NMR spectroscopy. Fmoc deprotection of the Dox-Peg-Rcp-Fmoc polymer is carried out to produce the Dox-Peg-Rcp polymer. The newly designed Dox-Peg-Rcp polymer shows nanoaggregation in water. In addition to that, they are soluble in water as well as biological media. The drug release profile at mild acidic condition shows the importance of having ester linker. CLSM images of Dox-Peg-Rcp nanoaggregates clearly show the efficient internalization into the living cells. MTT assays of Dox-Peg-Rcp nanoaggregates show that these nanoaggregates have a greater anticancer efficacy. To the best of our knowledge, this is the first report on water-soluble polyacetylenes for biological/drug delivery applications.

Biodegradable Copolymer for Stimuli-Responsive Sustained Release of Doxorubicin.

Pendent functionalization of biodegradable polymers provides unique importance in biological applications. In this work, we have synthesized a polymeric nanocarrier for the controlled release of the anticancer drug doxorubicin (DOXI). Inspired by the pH responsiveness of acylhydrazine bonds along with the interesting self-assembly behavior of amphiphilic copolymers, this report delineates the development of a PEG-SS-PCL-DOXI copolymer consisting of DOXI, PEG, and a caprolactone backbone. First, the inclusion of a PEG moiety in the copolymer helps to achieve biocompatibility and aqueous solubility as well as a prolonged circulation time of the nanocarrier. Second, an acid-sensitive acylhydrazine-based linkage is chosen to attach DOXI to trigger sustained drug release, whereas the inclusion of an enzymatically cleavable disulfide linkage in the backbone adds to the advantage of backbone biodegradability at the intracellular level.

Efficient approach to prepare multiple chemotherapeutic agent conjugated nanocarrier.

A pH-responsive, multiple chemotherapeutic agent derived nanocarrier has been synthesized by conjugating doxorubicin, indomethacin, and folate to the backbone of norbornene polymer. Drug molecules are connected to the norbornene backbone by an ester linker to demonstrate the pH-responsive capabilities. The complete chemical and biological properties of the new norbornene-based polymeric nanocarrier, intended for combination cancer chemotherapy, are discussed.

Magnetic norbornene polymer as multiresponsive nanocarrier for site specific cancer therapy.

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.