Tumor associated macrophage-targeted microRNA delivery with dual-responsive polypeptide nanovectors for anti-cancer therapy

Liu, Lanlan1; Yi, Huqiang1,2; He, Huamei1; Pan, Hong1; Cai, Lintao1; Ma, Yifan1

2017-07

10.1016/j.biomaterials.2017.04.043

BIOMATERIALS   影响因子和分区

0142-9612

1878-5905

Repolarizing Tumor-associated macrophages (TAMs) to anti-tumor M1 macrophages with microRNA (miR) is a plausible approach for cancer treatment. However, how to achieve TAM-targeted miR delivery remains a challenge. The present study generated redox/pH dual-responsive hybrid polypeptide nanovectors, which consisted of self-crosslinked redox-responsive nanoparticles based on galactosefunctionalized n-butylamine-poly(L-lysine)-b-poly(L-cysteine) polypeptides (GLC) coated with DCAgrafted sheddable PEG-PLL (sPEG) copolymers. The ex vivo study showed that sPEG shielded cationic GLC core at physiological pH but quickly shed off to re-expose GLC due to it charge reversible property. Encapsulation with sPEG/GLC nanovectors effectively facilitated macrophage-targeted miR delivery at the acidic condition but diminished miR uptake at neutral pH. Administration of miR155-loaded sPEG/GLC (sPEG/GLC/155) nanocomplexes increased miR155 expression in TAMs about 100-400 folds both in vitro and in vivo. sPEG/GLC/155 also effectively repolarized immunosuppressive TAMs to anti-tumor M1 macrophages through elevating M1 macrophage markers (IL-12, iNOS, MHC II) and suppressing M2 macrophage markers (Msr2 and Arg1) in TAMs. Moreover, the treatment of sPEG/GLC/155 significantly increased activated T lymphocytes and NK cells in tumors, which consequently led to robust tumor regression. Hence, TAM-targeted delivery of miR with redox/pH dual-responsive sPEG/GLC nanovectors could be a promising approach to re-polarize TAMs to M1 macrophages in situ and induce tumor regression. (C) 2017 Published by Elsevier Ltd.

Tumor-associated macrophages Nanoparticles Targeted delivery miR155 Cancer therapy

SCI ; EI

英语

其他

SIAT Innovation Program for Excellent Young Researchers[201506]

Engineering ; Materials Science

Engineering, Biomedical ; Materials Science, Biomaterials

WOS:000401717500014

ELSEVIER SCI LTD

20171803625293

Amino acids ; Diseases ; Nanoparticles ; Oncology ; pH ; Polyethylene glycols ; Polyethylene oxides ; Polypeptides ; RNA ; Tumors

Bioengineering and Biology:461 ; Nanotechnology:761 ; Chemistry, General:801.1 ; Organic Compounds:804.1 ; Organic Polymers:815.1.1 ; Solid State Physics:933

MATERIALS SCIENCE

Web of Science

1.Chinese Acad Sci, Shenzhen Inst Adv Technol, Key Lab Hlth Informat, Guangdong Key Lab Nanomed, Shenzhen 518055, Peoples R China
2.Southern Univ Sci & Technol, Dept Mat Sci & Engn, Shenzhen 518055, Peoples R China

Liu, Lanlan,Yi, Huqiang,He, Huamei,et al. Tumor associated macrophage-targeted microRNA delivery with dual-responsive polypeptide nanovectors for anti-cancer therapy[J]. BIOMATERIALS,2017,134:166-179.

Liu, Lanlan,Yi, Huqiang,He, Huamei,Pan, Hong,Cai, Lintao,&Ma, Yifan.(2017).Tumor associated macrophage-targeted microRNA delivery with dual-responsive polypeptide nanovectors for anti-cancer therapy.BIOMATERIALS,134,166-179.

Liu, Lanlan,et al."Tumor associated macrophage-targeted microRNA delivery with dual-responsive polypeptide nanovectors for anti-cancer therapy".BIOMATERIALS 134(2017):166-179.