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Abstract
Aim: To build up a combined therapy strategy to address limitations of the enhanced permeability and retention (EPR) effect and improve the efficiency of tumor therapy. Materials & methods: A pH-sensitive nanocomplex for co-delivery of doxorubicin (DOX) and all-trans retinoic acid (ATRA) was developed based on nanodiamonds (DOX/ATRA-NDs) to enhance intracellular retention of drugs. Meanwhile, ultrasound was employed to enhance tumor vascular penetration of DOX-ATRA-NDs. Results: The distribution of DOX/ATRA-NDs in the tumor tissues increased threefold when ultrasound was applied at 1 MHz and 0.6 W/cm2. Comparing with unmodified chemotherapeutics, the combined therapy induced more tumor cells apoptosis and greater tumor growth inhibition in both liver and breast tumor models. Conclusion: DOX-ATRA-NDs demonstrate great potential in clinical applications.
Financial & competing interests disclosure
This work was supported by Chongqing Research Program of Basic Research and Frontier Technology (number cstc2015jcyjA50001), the National Natural Science Fund by the Chinese National Science Foundation (number 11574039) and the National Instrumentation Program (number 2013YQ030629). The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.
No writing assistance was utilized in the production of this manuscript.
Ethical conduct of research
All animals received care in compliance with the guidelines outlined in the Guide for the Care and Use of Laboratory Animals, and the procedures were approved by the Animal Care and Use Committee of Chongqing Medical University.