PMID- 29160061 OWN - NLM STAT- MEDLINE DCOM- 20181211 LR - 20181211 IS - 1944-8252 (Electronic) IS - 1944-8244 (Linking) VI - 9 IP - 49 DP - 2017 Dec 13 TI - A Dual Macrophage Targeting Nanovector for Delivery of Oligodeoxynucleotides To Overcome Cancer-Associated Immunosuppression. PG - 42566-42576 LID - 10.1021/acsami.7b13594 [doi] AB - To overcome cancer-associated immunosuppression, we prepared a dual-targeting vector to deliver CpG oligodeoxynucleotides (ODN) to macrophages. The dual-targeting system composed of mannosylated carboxymethyl chitosan (MCMC)/hyaluronan (HA) for macrophage targeting and protamine sulfate for ODN complexation was prepared by self-assembly. The effects of ODN delivery on immune cells was studied in J774A.1 cells. Due to the enhanced delivery efficiency, the dual-targeting delivery system exhibits a higher immune stimulatory activity compared with the monotargeting delivery system containing either MCMC or HA, resulting in a dramatically enhanced secretion of proinflammatory cytokines and a successful shift to activated macrophages (M1). Besides macrophages, the influence of the delivery system on tumor cells (MCF-7) was also investigated. In MCF-7 cells, the increased expressions of nuclear transcription factor-kappaB (NF-kappaB), PIK3R3, and phosphorylated protein kinase B (p-Akt) caused by activated NF-kappaB and phosphoinositide 3-kinase/Akt signalings were observed. Nevertheless, upregulated Fas as well as Fas ligand (FasL) may induce Fas/FasL-mediated apoptosis, which results in the increased expressions of caspases in tumor cells. FAU - He, Xiao-Yan AU - He XY AD - Key Laboratory of Biomedical Polymers of Ministry of Education, College of Chemistry and Molecular Sciences, Wuhan University , Wuhan 430072, People's Republic of China. FAU - Liu, Bo-Ya AU - Liu BY AD - Key Laboratory of Biomedical Polymers of Ministry of Education, College of Chemistry and Molecular Sciences, Wuhan University , Wuhan 430072, People's Republic of China. FAU - Wu, Jin-Long AU - Wu JL AD - Key Laboratory of Biomedical Polymers of Ministry of Education, College of Chemistry and Molecular Sciences, Wuhan University , Wuhan 430072, People's Republic of China. FAU - Ai, Shu-Lun AU - Ai SL AD - Key Laboratory of Biomedical Polymers of Ministry of Education, College of Chemistry and Molecular Sciences, Wuhan University , Wuhan 430072, People's Republic of China. FAU - Zhuo, Ren-Xi AU - Zhuo RX AD - Key Laboratory of Biomedical Polymers of Ministry of Education, College of Chemistry and Molecular Sciences, Wuhan University , Wuhan 430072, People's Republic of China. FAU - Cheng, Si-Xue AU - Cheng SX AUID- ORCID: 0000-0001-9611-4421 AD - Key Laboratory of Biomedical Polymers of Ministry of Education, College of Chemistry and Molecular Sciences, Wuhan University , Wuhan 430072, People's Republic of China. LA - eng PT - Journal Article DEP - 20171130 PL - United States TA - ACS Appl Mater Interfaces JT - ACS applied materials & interfaces JID - 101504991 RN - 0 (NF-kappa B) RN - 0 (Oligodeoxyribonucleotides) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) SB - IM MH - Humans MH - *Macrophages MH - NF-kappa B MH - Neoplasms MH - Oligodeoxyribonucleotides MH - Phosphatidylinositol 3-Kinases OTO - NOTNLM OT - CpG ODN OT - cancer treatment OT - gene delivery OT - immunotherapy OT - macrophage targeting OT - self-assembly EDAT- 2017/11/22 06:00 MHDA- 2018/12/12 06:00 CRDT- 2017/11/22 06:00 PHST- 2017/11/22 06:00 [pubmed] PHST- 2018/12/12 06:00 [medline] PHST- 2017/11/22 06:00 [entrez] AID - 10.1021/acsami.7b13594 [doi] PST - ppublish SO - ACS Appl Mater Interfaces. 2017 Dec 13;9(49):42566-42576. doi: 10.1021/acsami.7b13594. Epub 2017 Nov 30.