Magnetically and pH dual responsive dendrosomes for tumor accumulation enhanced folate-targeted hybrid drug delivery

Dendrosomes are new tumor targeted drug delivery systems to improve safety and therapeutic effects of antitumor agents. In this study we designed and synthesized magnetically and pH dual responsive dendrosomes with magnetic nanoparticles and folate-targeted dendrimers encapsulated in long-circulating pH sensitive liposomes. Cellular uptake and tissue penetration were assessed on cell lines and tumor spheroids respectively. Xenograft mice were used to study tumor accumulation. The dendrosomes were stable at pH 7.4, but responsively released their content at acidic pH. In slightly acid environments, the hybrid vectors showed similar cytotoxicity and cellular uptake to the free folate-dendrimers conjugate due to rapid release. The dendrosomes showed a greater cellular uptake by HeLa cells ( FA receptor positive) due to the conjugation with folic acid ( FA). In multicellular tumor spheroid tests, a slightly acidic environment and the application of magnet both promoted the permeation efficiency of the hybrid vectors. In the xenograft mice model both in vivo images and tissue distribution assessment indicated that the dendrosomes had higher peak intensity and a longer residence time. Through the synergistic effects of magnetic responsiveness and both passive and active targeting properties, the multi-functional dendrosomes were demonstrated to have great potential as a promising anticancer drug delivery platform. (C) 2016 Elsevier B.V. All rights reserved.