Shine bright, then fight: lectin-decorated gold nanostars for cancer theranostics.

Targeted drug delivery, including nanoparticle-based methods, offers promise for addressing traditional oncology challenges, however, cancers like triple-negative breast cancer lack common targets such as HER2, progesterone, and estrogen receptors. Developing targeted drugs based on non-classical receptor interactions is crucial for effective delivery across all tumor types. For example, altered glycosylation profiles in cancer cells can guide nanoparticles for chemo/photosensitizing treatments. Here we show that lectin-modified gold nanoparticles are effective agents for cancer theranostics. 70 nm gold nanostars, AuNS, possessing NIR-triggered photothermal properties were modified with a spectrum of phytolectins, allowing AuNS to interact with an altered glycosylation profile of cancer cells. Flow cytometry screening revealed that soybean agglutinin, SBA, is the best lectin for AuNS targeted delivery. In vitro toxicity studies demonstrated that 100% cell death was achieved for cells labeled with AuNS-SBA and irradiated with NIR light. In vivo studies confirmed that i.v.-administered fluorescent AuNS-SBA efficiently accumulated in BALB/c tumor allografts and generated a bright fluorescent signal in tumors. Moreover, after a single session of photothermal therapy, AuNS-SBA led to 100% tumor growth inhibition for large solid tumors (more than 200 mm3). The obtained results demonstrate that lectin-decorated AuNS hold the potential to enhance targeted delivery and cancer theranostics.