4.7 Article

Rhodiola rosea polysaccharides-based nanoparticles loaded with DOX boosts chemo-immunotherapy for triple-negative breast cancer by re-educating Tumor-associated macrophages

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DOI: 10.1016/j.ijbiomac.2023.124110

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Rhodiola rosea polysaccharides; Breast cancer; Polysaccharides -based nanoparticle; Chemo-immunotherapy; Tumor -associated macrophages

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In this study, Rhodiola rosea polysaccharides (RHPs) were used as an immunoactive vector for hydrophobic drug delivery by chemically modifying folic acid (FA) and stearic acid (SA) to obtain FA-RHPs-SA derivatives. The hydrophobic drug doxorubicin (DOX) was efficiently encapsulated in the FA-RHPs-SA, which exhibited uniform size distribution and pH-sensitive release capacity. Furthermore, the FA-RHPs-SA showed modulatory effects on tumor-associated macrophages and demonstrated superior antitumor activity compared to DOX monotherapy.
Hydrophobic drug delivery vectors suffer significant challenges in cancer therapy, including efficient encapsu-lation and tumor targeting ability. In the present study, Rhodiola rosea polysaccharides (RHPs), which have the ability to modulate Tumor-associated macrophages and typical structural characteristics, were employed as an immunoactive vector for drug delivery. Folic acid (FA) and stearic acid (SA) were chemically modified to the backbone of RHPs to obtain the self-assembly and tumor-targeting behavior. Further, the hydrophobic drug, doxorubicin (DOX), was encapsulated in the RHPs derivatives (FA-RHPs-SA) with high efficiency. Additionally, the optimally formed DOX@FA-RHPs-SA had a uniform size distribution of approximately 196 nm and a pH -sensitive release capacity in different acidic conditions. In vitro experiments demonstrated that tumor cells could efficiently uptake DOX@FA-RHPs-SA. Furthermore, the modulatory function of the FA-RHPs-SA on RAW264.7 macrophages was also demonstrated in the transition from M0 to M1 phenotypes, and the M2 differentiated into the M1. Finally, the in vivo antitumor study revealed that the inhibitory effect of DOX@FA-RHPs-SA was superior to the DOX monotherapy treatment, and the new preparation functioned synergistically by inducing tumor cell apoptosis and modulating immune cell function. In conclusion, this study described an RHPs-based hydrophobic delivery vector and achieved an additional helpful antitumor effect by modulating Tumor -associated macrophages.

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