Colorectal cancer (CRC) is the second leading cause of cancer deaths in the United States; the predominant cause for mortality is metastasis to distant organs (e.g., lung). A major problem limiting the success of chemotherapy in metastatic CRC is the inability to target tumor tissues selectively and avoid severe side effects to normal tissues and organs. Here, we demonstrate polymeric nanoparticles (PNPs) entrapping chemotherapeutic agents provide a new therapeutic option for treating CRC that has metastasized to the lung. PNPs assembled from FDA approved biocompatible block copolymer accumulated predominantly in lung tissue. PNPs showed negligible accumulation in liver, spleen and kidneys, which was confirmed by fluorescent nanoparticle imaging and analysis of PI3K inhibition in the organs. PNPs entrapping PI3K inhibitors (i.e., wortmannin and PX866) suppressed CRC lung metastasis growth, and SN-38-loaded PNPs completely eliminated CRC lung metastasis. Our results demonstrate that polymer-drug nanoparticles offer a new approach to reduce toxicity of cancer therapy and has the potential to improve outcomes for patients with lung metastasis.
|Number of pages||7|
|Journal||Journal of Controlled Release|
|State||Published - Apr 10 2018|
Bibliographical noteFunding Information:
The authors thank the Markey Cancer Center's Research Communications Office for help with manuscript preparation. We also thank the Biostatistics and Bioinformatics and the Biospecimen Procurement and Translational Pathology Shared Resource Facilities of the Markey Cancer Center for statistical analysis and histologic assessment, respectively. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of the grant funding agencies. This study was supported by grants P30 CA177558 , R01 CA195573 , and R01 DK048498 from the National Institutes of Health (NIH).
© 2018 The Authors
- CRC lung metastasis
- Colorectal cancer
- Nanoparticle therapeutics
- PI3K inhibitors
- Polymeric nanoparticles
ASJC Scopus subject areas
- Pharmaceutical Science