Harnessing Viral Nanoparticles for Targeted Cancer Therapy

Human papillomavirus nanoparticles (HPV-NPs) have shown a natural preference for tumor cells, which could be attributed to the overexpression of heparan sulfate proteoglycans (HSPG) in the extracellular matrix of tumors. This affinity has been harnessed for the targeted treatment of ovarian carcinoma and uveal melanoma using α-particle radiation and photodynamic therapy (PDT), respectively. In vivo studies have confirmed the selective targeting of HPV-NPs to tumor tissues, as evidenced by the detection of luciferase signals in tumor-bearing animals. The therapeutic efficacy of HPV-NPs was further demonstrated through the use of AU-010, a conjugate of a chelator and HPV-NPs, radiolabeled with Th-227. This treatment significantly improved survival rates compared to control groups. Ongoing experiments are focusing on optimizing chelators and testing in additional animal models.

In the realm of PDT, AU-011, an HPV-NP conjugated with IR700 dye, was developed. Upon exposure to 690 nm near-infrared light, AU-011 generates reactive oxygen species that are lethal to bound cells. In vitro studies revealed that AU-011 has a higher binding capacity and is more potent than Trastuzumab-IR700, with an IC50 value of 5.6 pM compared to 1.6 nM for Trastuzumab-IR700. The effectiveness of AU-011 was also confirmed in a range of uveal melanoma cell lines. With the FDA approval of 690 nm light for PDT in ophthalmology, in vivo studies for AU-011 in uveal melanoma are currently in progress, indicating a promising path towards clinical development.