1 research outputs found
Inhibition of Thioredoxin Reductase by Targeted Selenopolymeric Nanocarriers Synergizes the Therapeutic Efficacy of Doxorubicin in MCF7 Human Breast Cancer Cells
Increasing evidence
suggests selenium nanoparticles (Se NPs) as potential cancer therapeutic
agents and emerging drug delivery carriers, yet, the molecular mechanism
of their anticancer activity still remains unclear. Recent studies
indicate thioredoxin reductase (TrxR), a selenoenzyme, as a promising
target for anticancer therapy. The present study explored the TrxR
inhibition efficacy of Se NPs as a plausible factor impeding tumor
growth. Hyaluronic acid (HA)-functionalized selenopolymeric nanocarriers
(Se@CMHA NPs) were designed wielding chemotherapeutic potential for
target specific Doxorubicin (DOX) delivery. Se@CMHA nanocarriers are
thoroughly characterized asserting their chemical and physical integrity
and possess prolonged stability. DOX-loaded selenopolymeric nanocarriers
(Se@CMHA-DOX NPs) exhibited enhanced cytotoxic potential toward human
cancer cells compared to free DOX in an equivalent concentration eliciting
its selectivity. In first-of-its-kind findings, selenium as Se NPs
in these polymeric carriers progressively inhibit TrxR activity, further
augmenting the anticancer efficacy of DOX through a synergistic interplay
between DOX and Se NPs. Detailed molecular studies on MCF7 cells also
established that upon exposure to Se@CMHA-DOX NPs, MCF7 cells endure
G2/M cell cycle arrest and p53-mediated caspase-independent apoptosis.
To gauge the relevance of the developed nanosystem in in vivo settings,
three-dimensional tumor sphere model mimicking the overall tumor environment
was also performed, and the results clearly depict the effectiveness
of our nanocarriers in reducing tumor activity. These findings are
reminiscent of the fact that our Se@CMHA-DOX NPs could be a viable
modality for effective cancer chemotherapy