Application of fluorocarbon nanoparticles of ¹³¹I-fulvestrant as a targeted radiation drug for endocrine therapy on human breast cancer

Breast cancer is the most prevalent malignant tumor among women, with hormone receptor-positive cases constituting 70%. Fulvestrant, an antagonist for these receptors, is utilized for advanced metastatic hormone receptor-positive breast cancer. Yet, its inhibitory effect on tumor cells is not strong, and it lacks direct cytotoxicity. Consequently, there's a significant challenge in preventing recurrence and metastasis once cancer cells develop resistance to fulvestrant.

To address these challenges, we engineered tumor-targeting nanoparticles termed ¹³¹I-fulvestrant-ALA-PFP-FA-NPs. This involved labeling fulvestrant with ¹³¹I to create ¹³¹I-fulvestrant. Subsequently, we incorporated the ¹³¹I-fulvestrant and 5-aminolevulinic acid (ALA) into fluorocarbon nanoparticles with folate as the targeting agent. This design facilitates a tri-modal therapeutic approach—endocrine therapy, radiotherapy, and PDT for estrogen receptor-positive breast cancer.

Our in vivo and in vitro tests showed that the drug-laden nanoparticles effectively zeroed in on tumors. This targeting efficiency was corroborated using SPECT-CT imaging, confocal microscopy, and small animal fluorescence imaging. The ¹³¹I-fulvestrant-ALA-PFP-FA-NPs maintained stability and showcased potent antitumor capabilities due to the synergism of endocrine therapy, radiotherapy, and CR-PDT. Throughout the treatment duration, we detected no notable irregularities in hematological, biochemical, or histological evaluations.

We've pioneered a nanoparticle system loaded with radioactive isotope ¹³¹I, endocrine therapeutic agents, and a photosensitizer precursor. This system offers a combined modality of radiotherapy, endocrine treatment, and PDT for breast cancer.