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

Int J Biol Macromol. 2023 Mar 21:124110. doi: 10.1016/j.ijbiomac.2023.124110. Online ahead of print.ABSTRACTEfficient encapsulation and tumor targeting ability are the key issues for hydrophobic drugs delivery vectors in cancer therapy. In the current study, Rhodiola rosea polysaccharides (RHPs) serve as an immunoactive vector for drug delivery with tumor-associated macrophages (TAMs) modulating ability and typical structural characteristics. Firstly, Folic acid (FA) and stearic acid (SA) were chemically modified to the backbone of RHPs to obtain the self-assemble and tumor targeting behaviors. Then, the hydrophobic drug (Doxorubicin, DOX) was encapsulated in the RHPs derivatives (FA-RHPs-SA) with high efficiency. Moreover, the optimal formed DOX@FA-RHPs-SA were around 196 nm with uniform size distribution and a pH-sensitive release capacity in different acidic conditions. In vitro experiments demonstrated that DOX@FA-RHPs-SA could efficiently uptake by tumor cells. 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, 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 worked synergistically by inducing tumor cell apoptosis and modulating immune cell function. In summary, this study describes a RHPs-based hydrophobic delivery vector and achiev...
Source: International Journal of Biological Macromolecules - Category: Biochemistry Authors: Source Type: research