Astragalus polysaccharide-superparamagnetic iron oxide nanocomposite for tumor-associated macro-phage M1 polarization
OBJECTIVE To prepare and characterize Astragalus polysaccharide-superparamagnetic iron oxide nanocom-plexes(APS-SPIONs)and determine their efficiency in an intratumoral delivery of Astragalus polysaccharide(APS),focusing upon their impact on tumor-associated macrophage polarization.METHODS Initially,small-sized SPIONs were synthesized by a solvothermal method.APS-SPIONs were then successfully developed through a EDC/NHS coupling approach.Pharmaceuti-cal behaviors of APS-SPIONs were analyzed by dynamic light scattering and transmission electron microscopy.Iron and polysac-charide contents were quantitatively assessed by serum iron concentration assays and spectrophotometry.In vitro,the authors examined the influence of APS-SPIONs on RAW264.7 polarization by flow cytometry.A Transwell co-culture system was estab-lished involving RAW264.7 macrophages and 4T1 breast cancer cells for examining the interaction between drug dosing,macro-phage polarization and tumor cell proliferation.The inhibition of APS against 4T1 tumor growth through different dosing modes was examined and induction of tumor-associated macrophage(TAMs)M1 polarization and their anti-tumor efficacy evaluated.RESULTS APS-SPIONs exhibited an average particle size of(52.1±2.8)nm and a zeta poten(-21.1±0.7)mV.Polysac-charide and iron contents were 8.69％and 7.04％,respectively.APS-SPIONs effectively induced RAW264.7 polarization into M1 phenotype in vitro,resulting in enhanced breast cancer cell killing in co-culture system.Furthermore,APS's intratumoral delivery efficiency was correlated positively with its inhibition of 4T1 in situ tumors.After a treatment of APS-SPIONs,the polar-ization of murine TAMs toward M1 phenotype spiked markedly,leading to comprehensive anti-tumor efficacy enhancement.CONCLUSION SPIONs can enhance intratumoral APS delivery efficiency,further enhance the role of APS in promoting the polarization of TAMs M1 in situ 4T1 breast cancer mice.It provides strategies for traditional Chinese medicine to improve immune microenvironment and exert anti-tumor effects.
Astragalus polysaccharidesuperparamagnetic iron oxide nanoparticlestumor-associated macrophagesimmuno-therapy for breast cancer
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