Enhanced tumor therapy via drug co-delivery and in situ vascular-promoting strategy

Abstract

Conventional tumor starving therapy by reducing its vessel density may be effective at early treatment but potentially contributes to tumor hypoxia, drug resistance and metastasis. A new strategy through enhancing tumor angiogenesis in combination with effective chemotherapeutic drugs, has shown successful tumor growth and spread inhibition. To achieve in situ release of angiogenic and antitumor drugs in tumor, we designed a precise ratiometric polymeric hybrid micelle system for co-delivering nitric oxide and paclitaxel. The hybrid micelles could accumulate in tumor via the long blood circulation and enhanced permeability and retention (EPR) effect, promote the drug accumulation and penetration in tumor by in situ increased vascular permeability, blood perfusion and vessel density, achieve the synergistic antitumor effect of nitric oxide and paclitaxel through modified tumor microenvironment, overcome multidrug resistance and inhibit metastasis. This study presents a combinational therapy against tumor progression and spread, which shows great potential in cancer therapy of the future.