Delivery of siHIF ‐1α to Reconstruct Tumor Normoxic Microenvironment for Effective Chemotherapeutic and Photodynamic Anticancer Treatments

An integrated amphiphilic delivery system (RSCD) based on Angiotensin II receptor blocker candesartan for siRNA against the hypoxia-inducible factor-1 alpha (HIF-1 α) is fabricated, aiming at both vascular and cellular “relaxation” to reconstruct a tumor normoxic microenvironment, which significantly improves the chemotherapeutic and photodynamic anticancer treatment. AbstractThe tumor hypoxic microenvironment not only induces genetic and epigenetic changes in tumor cells, immature vessels formation for oxygen demand, but also compromises the efficiency of therapeutic interventions. On the other hand, conventional therapeutic approaches which kill tumor cells or destroy tumor blood vessels to block nutrition and oxygen supply usually facilitate even harsher microenvironment. Thus, simultaneously relieving the strained response of tumor cells and blood vessels represents a promising strategy to reverse the adverse tumor hypoxic microenvironment. In the present study, an integrated amphiphilic system (RSCD) is designed based on Angiotensin II receptor blocker candesartan for siRNA delivery against the hypoxia-inducible factor-1 alpha (HIF-1 α), aiming at both vascular and cellular “relaxation” to reconstruct a tumor normoxic microenvironment. Both in vitro and in vivo studies have confirmed that the hypoxia-inducible HIF-1α expression is down-regulated by 70% and vascular growth is inhibited by 60%. The “relaxation” therapy e nables neovascularization with more c...
Source: Small - Category: Nanotechnology Authors: Tags: Research Article Source Type: research