The synthesis and complete characterization of both norbornene-derived doxorubicin (mono 1) and polyethylene glycol (mono 2) monomers are clearly described, and their copolymerization by ring-opening metathesis polymerization (ROMP) to get the block copolymer (COPY-DOX) is vividly elaborated. The careful design of these conjugates exhibits properties like well-shielded drug moieties and well-defined nanostructures; additionally, they show solubility in both water and biological medium and also have the important tendency of rendering acid-triggered drug release. The drug release profile suggests 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. It is also observed that the drug release from micelles of COPY-DOX is significantly accelerated at a mildly acidic pH of 5.5-6, compared to the physiological pH of 7.4, suggesting the pH-responsive feature of the drug delivery system with hydrazone linkages. Confocal laser scanning microscopy (CLSM) measurements indicate that these COPY-DOX micelles are easily internalized by living cells. MTT assays against HeLa and 4T cancer cells showing COPY-DOX micelles have a high anticancer efficacy. All of these results demonstrate that these polymeric micelles that self-assembled from COPY-DOX block copolymers have great scope in the world of medicine, and they also symbolize promising carriers for the pH-triggered intracellular delivery of hydrophobic anticancer drugs.

A unique polymersome from amphiphilic, norbornene-derived thiobarbiturate homopolymers (NDTH) and its application as nanocarrier for cancer therapy are elaborately discussed. Various experiments like structural characterizations, control studies, cell viability studies, encapsulation studies, and MTT assay against 4T cancer cells are performed on these NDTH polymersomes to substantiate our claims. All of these results demonstrate that these self-assembled NDTH vesicles have great scope in the world of medicine, and they also symbolize promising carriers for the stimuli-triggered intracellular delivery of hydrophobic drugs. ■ INTRODUCTIONThe field of polymer vesicles (polymersomes) has the phenomenal record of consistent development over the last ten years. 1−3 The ability of amphiphilic block copolymers to self-assemble in selective solvents has been widely studied. 4 The self-assembled polymersomes are at the forefront of this nanotechnological revolution. 5−10 The current research theme of soft-nanotechnology is using polymersomes in the medical applications as nontoxic and targeted drug-delivery agents. 11 Though several types of nanocarriers have been proposed for biomedical purposes, 12,13 polymersomes (structures similar to lipid vesicles) represent an excellent candidate for medical applications. 14−16 These structures are more stable than liposomes but retain their low immunogenicity. But, we are here very specific among the polymersomes formed by the self-assembly of amphiphilic homopolymers, 17−21 for their fundamental perspectives along with their potential applications in drug delivery, nanotechnology and as model systems of biomembranes. 22−27 Self-assembly due to the strong hydrogen bonding nature, remains a subject of interest in the field of supramolecular chemistry. 28 Pioneering work in recognition-induced polymersomes (RIPs) are well-known in the literature. These RIPs are spontaneously formed from a threepoint hydrogen bonding recognition dyads. However, these recognition sensitive structures cannot be used in biomedical applications, due to the complex synthesis and the use of nonpolar media.Living ring-opening metathesis polymerization (ROMP) is more attractive due to the exceptional functional group tolerance of the Grubbs' catalyst employed in the polymerization process. 29−37 Here we have come up with a pH-and lipidsensitive polymersomes from a new molecular architecture, an amphiphilic, norbornene-derived thiobarbiturate homopolymers, NDTH. On the basis of the hydrophobicity and hydrophilicity of the solvent, the molecular orientation of NDTH is systematically modified. The role of hydrophilic headgroup is enacted by the thiobarbiturate functionality of each monomer unit in NDTH while the norbornene backbone behaves as a hydrophobic moiety. Polymersomes formed by the hydrophilic thiobarbiturate head groups attached to each repeating unit of the hydrophobic norbornene backbone will have greater stability and also are capable of spontaneously responding to their environmental conditions, s...

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.

Biocompatible nanocarriers conjugated with magnetic nanoparticle, doxorubicin and poly(ethylene oxide) (PEG) motif have been designed (PVLPEG-PVLDOXI-PCL-PHOS) to create a magnetic vector under magnetic field. Acylhydrazine linker is used to release the drug exactly at the mild acidic conditions resembling the pH of the cancerous cells. All the monomers and polymers are characterized carefully by the routine analytical techniques. Thermogravimetric analysis (TGA), FT-IR spectroscopy and scanning electron microscope (SEM) techniques are employed to confirm the anchoring of iron particle (Fe 3 O 4 ) to the PVLPEG-PVLDOXI-PCL-PHOS. Reservoir capabilities of the newly designed biodegradable nanocarrier are tested by both dynamic light scattering (DLS) and transmission electron microscopy (TEM). Drug release profile from nanocarrier is monitored by fluorimeter. The release profile shows the importance of having the acylhydrazine linker that helps to release the drug at the mild acidic conditions similar to cancerous cells. Confocal laser scanning microscopy (CLSM) and flow cytometry studies on 4T cells indicate that nanocarriers from PVLPEG-PVLDOXI-PCL-PHOS polymer are internalized efficiently. It is very interesting to note that the nanocarriers have exhibited both biologically and magnetically targeting abilities toward 4T cells in vitro.

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Mesoporous silica nanoparticles (MSNs) with stimuli-responsive gatekeepers have been extensively investigated for controlled drug delivery at the target sites. Herein, we developed reactive oxygen species (ROS)-responsive MSNs (R-MSNs), consisting of a gadolinium (Gd)-DOTA complex as the ROS-responsive gatekeeper and polyethylene glycol (PEG)-conjugated chlorin e6 as the ROS generator, for magnetic resonance (MR) imaging-guided photodynamic chemotherapy. Doxorubicin (DOX), chosen as an anticancer drug, was physically encapsulated into DOTA-conjugated MSNs, followed by chemical crosslinking via the addition of GdCl3. DOX-R-MSNs could effectively maintain their structural integrity in a physiological environment for 7 days and show an enhanced in vitro T1-MR imaging signal for the Gd-DOTA complex. Upon 660 nm laser irradiation, the release rate of DOX from DOX-R-MSNs remarkably increased along with the disintegration of the gatekeeper, whereas DOX release was significantly retarded without irradiation. When DOX-R-MSNs were intravenously injected into tumor-bearing mice, they were effectively accumulated in tumor tissue, which was demonstrated using MR imaging. In addition, tumor growth was significantly suppressed by DOX-R-MSNs, allowing for site-specific release of DOX in a photodynamically maneuvered manner. Overall, these results suggest that R-MSNs have potential as drug carriers for MR imaging-guided photodynamic chemotherapy.

Synthesis of norbornene derived phosphonate (1), poly-D-lysine (2), and phopholipid (3) monomers and their complete characterizations are studied. Ring-opening metathesis polymerizations (ROMP) of monomers (1-3) produce well-defined copolymers, CP(1) and CP(2). (1)H NMR along with FT-IR spectroscopy characterization confirms the copolymer formation, while gel permeation chromatography (GPC) analysis suggests the formation of polymers with fairly narrow molecular weight distributions. Upon following the well-known ligand exchange methods these copolymers produce CdSe-bound copolymers, CP(3) and CP(4). Dynamic light scattering and transmission electron microscopy measures the size of these CdSe bound copolymers, while (31)P NMR suggests the formation of CP(3) and CP(4). The results from the experiments of these copolymers on Neuro2A cells suggest that the novel PDL-anchored nanomaterial show their ability to polarize neuronal growth and differentiation.

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.