From Ancient Medicine to Targeted Nanocarrier: A Sparganii Rhizoma-Derived Nanoparticle for Diagnostic Imaging and Endocrine Therapy in Cancer.

The traditional Chinese medicine Sparganii Rhizoma has a long history in the treatment of gynecological diseases. In our previous work, we found that an extract of Sparganii Rhizoma had antitumor activity, attributed to the aluminum-rich polysaccharide, "SpaTA", which we isolated. SpaTA can selectively regulate the estrogen receptor, but its mechanism of antitumor activity is poorly understood. In the present study, we found that SpaTA naturally exists as a nanoparticle with a regular physical morphology. SpaTA induced apoptosis in human breast cancer cells mainly through interaction with estrogen receptors, ERα and GPR30, followed by activation of the PI3K/Akt and MEK/ERK pathways. Notably, cells also adjusted their cytoskeletal plasticity in response to SpaTA, which inhibited cell motility by suppressing focal adhesion and cytoskeleton reorganization via FAK. On the basis of these antitumor effects, we further modified SpaTA by conjugating it with the near-infrared dye, ICG, and loading the particles with the TGFβ inhibitor, LY2157299, to form the tumor-targeting nanomedicine, "SpaTAX". The application of SpaTAX to breast cancer models enables a dual use regimen: a single dose for fluorescence imaging of the tumor site, where SpaTAX accumulates due to the enhanced permeability and retention effect, and a multidose for antitumor treatment through estrogen receptor- and TGFβ-related signaling pathways. The synergetic roles of estrogen receptors and TGFβ pathways are responsible for SpaTAX-induced reinforced suppression on tumor growth. Finally, we assessed the biosafety of the formulation and found that SpaTAX is highly tolerable and may therefore be considered safe for future clinical theranostic application. Altogether, our results demonstrated a superior tumor targeting ability of SpaTA both in diagnostic imaging and endocrine therapy and also proved SpaTA as a promising nanocarrier with a high therapeutic capacity and a favorable modification potential.