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This study investigated how to effectively design teacher professional development to help teachers deepen their understanding of mathematics content related to the CCSSM (2010) and NGSS standards with topics related to nanotechnology. A design research approach was used. A team of scientists, mathematicians, math educators and science educators designed the integrated professional development to support teachers to strengthen their content knowledge and make interdisciplinary connections using nanotechnology. There were four iterations of the professional development across a western state. The pre and post test data revealed that teacher knowledge increased across the sites. The professional development design team became more effective in supporting teacher learning by carefully sequencing disciplines. A framework for STEM integration is also presented.