Folate receptor-targeted RNAi nanoparticles for silencing STAT3 in tumor-associated macrophages and tumor cells
We developed a STAT3 silencing siRNA to both tumor cells and M2 macrophages. The dual-targeting system prepared by electronic self-assembly was composed of folic acid-conjugated carboxymethyl chitosan for targeting and cationic chitosan derivatives for siRNA package. The effects of siRNA delivery wa...
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Veröffentlicht in: | Nanomedicine 2020-04, Vol.25, p.102173-102173, Article 102173 |
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Sprache: | eng |
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Zusammenfassung: | We developed a STAT3 silencing siRNA to both tumor cells and M2 macrophages. The dual-targeting system prepared by electronic self-assembly was composed of folic acid-conjugated carboxymethyl chitosan for targeting and cationic chitosan derivatives for siRNA package. The effects of siRNA delivery was investigated in M2 macrophages and Lewis lung cancer cells (LLC). Due to the enhanced delivery efficiency, the dual-targeting delivery system exhibited a higher efficacy compared with non-targeting nanoparticles, resulting in a dramatically reduction of STAT3 expression in both cells, and a successful shift from M2 phenotypes (pro-tumor) to M1 phenotypes (anti-tumor) for macrophages. Additionally, the influence of the nanoparticles on LLC cells co-cultured with M2 macrophages was also investigated. The increased apoptosis and inhibition of proliferation of LLC cells were observed. In vivo therapeutic effect was also evaluated in s.c. tumor models, tumor growth was effectively inhibited and the level of M2 macrophages in tumor tissues was dramatically reduced.
Folic acid was used as a targeting ligand and chitosan derivatives were used as vectors to construct nanoparticles loaded which could realize targeted delivery of STAT3 silencing siRNA sequences into tumor cells and M2 type tumor-associated macrophages. The inhibition of STAT3 expression in both types of cells could promote tumor cell apoptosis and on the other hand switch TAMs from the immunosuppressive M2 phenotype to the tumor-suppressed M1 phenotype, exerting an enhanced inhibitory effect against tumor cells. [Display omitted] |
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ISSN: | 1549-9634 1549-9642 |
DOI: | 10.1016/j.nano.2020.102173 |