TY - JOUR
T1 - Targeted delivery of oligonucleotides into tumor-associated macrophages for cancer immunotherapy
AU - Huang, Zhen
AU - Zhang, Zhengping
AU - Jiang, Yucui
AU - Zhang, Dachuan
AU - Chen, Jiangning
AU - Dong, Lei
AU - Zhang, Junfeng
N1 - Funding Information:
This work was supported by the National Science Fund for Distinguished Young Scholars ( 81025019 ), the National Natural Science Foundation of China ( 31071232 , 31170571 , 51173076 , 91129712 and 81102489 ), the Key Project of the Chinese Ministry of Education ( 108059 ), the Ph.D. Programs Foundation of the Chinese Ministry of Education ( 20100091120020 ), and the Jiangsu Provincial Natural Science Foundation of China ( BK 2009237 ).
PY - 2012/3/10
Y1 - 2012/3/10
N2 - Tumor-associated macrophages (TAMs) have been proven to be a driving force in the initiation, proliferation, metastasis and angiogenesis of various tumors. Specifically, alterations in the functions of TAMs exhibited inhibitory effects on tumor growth. However, there is currently no research being conducted on the targeting delivery of drugs into TAMs for cell-specific tumor immunotherapy. In the present study, we developed a TAMs targeted delivery system that is triggered by the acidic microenvironment in the tumor to release a TAMs-recognizing nano-complex loaded with oligonucleotides. By using this system, we demonstrated a significant anti-tumor effect of an oligonucleotide combination of CpG oligonucleotide, anti-IL-10 and anti-IL-10 receptor oligonucleotides. These nucleic acid drugs delivered by the delivery system accumulated in the TAMs of an allograft hepatoma murine model by intravenous injection, suppressed the pro-tumor functions and stimulated the anti-tumor activities of TAMs. More importantly, the nucleic acid drug-based immune-regulation was restricted to the tumor microenvironment and did not cause an upregulation of serum inflammatory cytokines. Our present study provides an effective therapeutic strategy for regulating cell-specific functions using nucleic acid drugs.
AB - Tumor-associated macrophages (TAMs) have been proven to be a driving force in the initiation, proliferation, metastasis and angiogenesis of various tumors. Specifically, alterations in the functions of TAMs exhibited inhibitory effects on tumor growth. However, there is currently no research being conducted on the targeting delivery of drugs into TAMs for cell-specific tumor immunotherapy. In the present study, we developed a TAMs targeted delivery system that is triggered by the acidic microenvironment in the tumor to release a TAMs-recognizing nano-complex loaded with oligonucleotides. By using this system, we demonstrated a significant anti-tumor effect of an oligonucleotide combination of CpG oligonucleotide, anti-IL-10 and anti-IL-10 receptor oligonucleotides. These nucleic acid drugs delivered by the delivery system accumulated in the TAMs of an allograft hepatoma murine model by intravenous injection, suppressed the pro-tumor functions and stimulated the anti-tumor activities of TAMs. More importantly, the nucleic acid drug-based immune-regulation was restricted to the tumor microenvironment and did not cause an upregulation of serum inflammatory cytokines. Our present study provides an effective therapeutic strategy for regulating cell-specific functions using nucleic acid drugs.
KW - Cancer immunotherapy
KW - Nucleic acid drugs
KW - Targeting delivery
KW - Tumor associated macrophage
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U2 - 10.1016/j.jconrel.2011.11.013
DO - 10.1016/j.jconrel.2011.11.013
M3 - Article
C2 - 22119956
AN - SCOPUS:84858697942
SN - 0168-3659
VL - 158
SP - 286
EP - 292
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 2
ER -