Doxorubicin-DNA adduct entrenched and motif tethered artificial virus encased in pH-responsive polypeptide complex for targeted cancer therapy

Abstract

Doxorubicin is a broad spectrum anticancer antibiotic that possesses toxic effects such as cardiomyopathy, that even lead to congestive heart failure. Thus, the development of a new bio-inspired system is required, that retain the advantageous effect of doxorubicin while retarding the side effects. Hence, a system was developed that we describe ‘doxorubicin-DNA adduct entrenched artificial virus encased in polypeptide complex’. The drug-DNA adduct (DDA) was prepared by a formaldehyde mediated reaction. A simple chloroform extraction method for the separation of DDA was developed. DDA was employed to self-assemble the folate tethered bovine serum albumin to form the protein coat in the proposed artificial virus. The folate tethered albumin provides an artificial virus concept, with tumor tissue targeting due to the presence of folate. The whole system was then encased in a pH-responsive polypeptide complex that dissolves in acidic pH, but not in basic pH. DDA was evaluated by UV–Vis spectrophotometry, spectrofluorimetry and high-performance liquid chromatography (HPLC). A promising drug release at physiological condition was observed from DDA. The developed system was evaluated by a developed and validated artificial cell apparatus that mimic the features of a cancer cell. The drug delivery system displayed a considerable amount of drug release within 24 h. Moreover, the developed artificial virus system reduced angiogenesis caused by tumor cells in chick chorioallantoic membrane. Histopathology of treated chicken heart slices demonstrated that the developed artificial virus system reduces the tissue deformation and apoptosis in heart tissue slices, thus providing a new approach to prevent Dox-induced cardiomyopathy.