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...

Microglia are the resident macrophage-like populations in the central nervous system (CNS). Microglia remain quiescent, unable to perform effector and antigen presentation (APC) functions until activated by injury or infection, and have been suggested to represent the first line of defence for the CNS. Previous studies demonstrated that microglia can be persistently infected by neurotropic mouse hepatitis virus (MHV) which causes meningoencephalitis, myelitis with subsequent axonal loss, and demyelination and serve as a virus-induced model of human neurological disease multiple sclerosis (MS). Current studies revealed that MHV infection is associated with the pronounced activation of microglia during acute inflammation, as evidenced by characteristic changes in cellular morphology and increased expression of microglia-specific proteins, Iba1 (ionized calcium-binding adaptor molecule 1), which is a macrophage/microglia-specific novel calcium-binding protein and involved in membrane ruffling and phagocytosis. During chronic inflammation (day 30 postinfection), microglia were still present within areas of demyelination. Experiments performed in ex vivo spinal cord slice culture and in vitro neonatal microglial culture confirmed direct microglial infection. Our results suggest that MHV can directly infect and activate microglia during acute inflammation, which in turn during chronic inflammation stage causes phagocytosis of myelin sheath leading to chronic inflammatory demyelination.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the human central nervous system (CNS). Neurotropic demyelinating strain of MHV (MHV-A59 or its isogenic recombinant strain RSA59) induces MS-like disease in mice mediated by microglia, along with a small population of T cells. The mechanism of demyelination is at least in part due to microglia-mediated myelin stripping, with some direct axonal injury. Immunization with myelin oligodendrocyte glycoprotein (MOG) induces experimental autoimmune encephalomyelitis (EAE), a mainly CD4+ T-cell-mediated disease, although CD8+ T cells may play a significant role in demyelination. It is possible that both autoimmune and nonimmune mechanisms such as direct viral toxicity may induce MS. Our study directly compares CNS pathology in autoimmune and viral-induced MS models. Mice with viral-induced and EAE demyelinating diseases demonstrated similar patterns and distributions of demyelination that accumulated over the course of the disease. However, significant differences in acute inflammation were noted. Inflammation was restricted mainly to white matter at all times in EAE, whereas inflammation initially largely involved gray matter in acute MHV-induced disease and then is subsequently localized only in white matter in the chronic disease phase. The presence of dual mechanisms of demyelination may be responsible for the failure of immunosuppression to promote long-term remission in many MS patients.

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