Chemotherapy based on HPMA copolymer conjugates with pH-controlled release of doxorubicin triggers anti-tumor immunity

被引:60
作者
Mrkvan, T [1 ]
Sirova, M
Etrych, T
Chytil, P
Strohalm, J
Plocova, D
Ulbrich, K
Rihova, B
机构
[1] ASCR, Inst Microbiol, Dept Immunol & Gnotobiol, Prague 14220, Czech Republic
[2] ASCR, Inst Macromol Chem, Dept Biomed Polymers, Prague 16206, Czech Republic
关键词
anti-cancer chemotherapy; doxorubicin; HPMA copolymer conjugates; anti-tumor immunity; EL4; lymphoma;
D O I
10.1016/j.jconrel.2005.09.028
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
A novel class of anti-cancer therapeutics - polymeric conjugates of N-(2-hydroxypropyl)methaerylamide (HPMA) copolymers and doxorubicin with pH-controlled release of the drug - is highly efficient in killing tumor cells in vitro and is potent in eradicating growing tumors in vivo. Moreover, in comparison with low-molecular-weight drugs, the macromolecular therapeutics show decreased acute as well as delayed adverse side-toxicity. More importantly, the polymeric conjugates trigger the onset of specific anti-tumor immune response and this anti-tumor immunity can be transferred with splenocytes to naive recipients. In other terms, chemotherapy based on conjugates of HPMA copolymer with doxorubicin possesses immunomodulating properties. This finding might also have wider implications for the management of relapsing tumors in human patients. (c) 2005 Elsevier B.V. All rights reserved.
引用
收藏
页码:119 / 129
页数:11
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