TY - JOUR
T1 - Polymeric micelles incorporating (1,2-diaminocyclohexane)platinum (II) suppress the growth of orthotopic scirrhous gastric tumors and their lymph node metastasis
AU - Rafi, Md
AU - Cabral, H.
AU - Kano, M. R.
AU - Mi, P.
AU - Iwata, C.
AU - Yashiro, M.
AU - Hirakawa, K.
AU - Miyazono, K.
AU - Nishiyama, N.
AU - Kataoka, K.
N1 - Funding Information:
This study was supported by Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program) from the Japan Society for the Promotion of Science (JSPS) and Grants-in-Aid for Scientific Research from the Japanese Ministry of Health, Labour, and Welfare (MHLW).
PY - 2012/4/30
Y1 - 2012/4/30
N2 - Nano-scaled drug carriers have great potential for the treatment of solid tumors. Nevertheless, hypovascularity and fibrosis in some types of solid tumors have been demonstrated to reduce the penetration and accumulation of nano-scaled drug carriers. Diffuse-type scirrhous gastric cancers present such characteristics as well as frequent metastasis to the lymph nodes; therefore, it remains a great challenge to eradicate scirrhous gastric cancers based on the drug targeting using nanocarriers. Herein, we demonstrated that polymeric micelles with 30-nm diameter incorporating (1,2-diaminocyclohexane)platinum(II) (DACHPt), the parent complex of the anticancer drug oxaliplatin, efficiently penetrated and accumulated in an orthotopic scirrhous gastric cancer model, leading to the inhibition of the tumor growth. Moreover, the elevated localization of systemically injected DACHPt-loaded micelles in metastastic lymph nodes reduced the metastatic tumor growth. These results suggest DACHPt-loaded micelles as a promising nanocarrier for the treatment of scirrhous gastric cancers and their lymphatic metastases.
AB - Nano-scaled drug carriers have great potential for the treatment of solid tumors. Nevertheless, hypovascularity and fibrosis in some types of solid tumors have been demonstrated to reduce the penetration and accumulation of nano-scaled drug carriers. Diffuse-type scirrhous gastric cancers present such characteristics as well as frequent metastasis to the lymph nodes; therefore, it remains a great challenge to eradicate scirrhous gastric cancers based on the drug targeting using nanocarriers. Herein, we demonstrated that polymeric micelles with 30-nm diameter incorporating (1,2-diaminocyclohexane)platinum(II) (DACHPt), the parent complex of the anticancer drug oxaliplatin, efficiently penetrated and accumulated in an orthotopic scirrhous gastric cancer model, leading to the inhibition of the tumor growth. Moreover, the elevated localization of systemically injected DACHPt-loaded micelles in metastastic lymph nodes reduced the metastatic tumor growth. These results suggest DACHPt-loaded micelles as a promising nanocarrier for the treatment of scirrhous gastric cancers and their lymphatic metastases.
KW - Chemotherapy
KW - Drug delivery
KW - Gastric cancer
KW - Lymph node metastasis
KW - Polymeric micelles
UR - http://www.scopus.com/inward/record.url?scp=84861099393&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84861099393&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2012.01.038
DO - 10.1016/j.jconrel.2012.01.038
M3 - Article
C2 - 22326402
AN - SCOPUS:84861099393
SN - 0168-3659
VL - 159
SP - 189
EP - 196
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 2
ER -