TY - JOUR
T1 - Colorectal cancer lung metastasis treatment with polymer–drug nanoparticles
AU - Rychahou, Piotr
AU - Bae, Younsoo
AU - Reichel, Derek
AU - Zaytseva, Yekaterina Y.
AU - Lee, Eun Y.
AU - Napier, Dana
AU - Weiss, Heidi L.
AU - Roller, Nick
AU - Frohman, Heather
AU - Le, Anh Thu
AU - Mark Evers, B.
N1 - Publisher Copyright:
© 2018 The Authors
PY - 2018/4/10
Y1 - 2018/4/10
N2 - 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.
AB - 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.
KW - CRC lung metastasis
KW - Colorectal cancer
KW - Nanoparticle therapeutics
KW - PI3K inhibitors
KW - Polymeric nanoparticles
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U2 - 10.1016/j.jconrel.2018.02.008
DO - 10.1016/j.jconrel.2018.02.008
M3 - Article
C2 - 29421609
AN - SCOPUS:85042391017
SN - 0168-3659
VL - 275
SP - 85
EP - 91
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -