Lignin-Based Nanocarrier for Simultaneous Delivery of 131I and SN-38 in the Combined Treatment of Solid Tumors by a Nanobrachytherapy Approach

<b>Background:</b> The rapid rise in cancer incidence significantly augments efforts to improve cancer treatments. A multimodal approach in the nanobrachytherapy of solid tumors is one of the promising methods under investigation. This study presents a novel biocompatible lignin-based nanomaterial, loaded with cytostatic agent SN-38 and radionuclide ¹³¹I, for simultaneous radiation and chemotherapy of solid tumors by a nanobrachytherapy approach. <b>Method:</b> Nanoparticles of ~100 nm in size, composed of lignin alone or loaded with 10% (m/m) of SN-38 (SN-38@lignin), were synthesized using a bottom-up approach and characterized. Subsequent radiolabeling of the nanoparticles by ¹³¹I produced ¹³¹I-lignin and ¹³¹I-SN-38@lignin. Their antitumor efficiency was tested against luciferase-expressing 4T1 mouse breast cancer xenografts of ~100 mm³ size on Balb/c mice. <b>Results:</b> An intratumoral injection of 1.85 MBq of ¹³¹I-lignin was retained within the tumor and achieved a moderate twofold decrease in tumor size compared to the control group. Injecting SN-38@lignin containing 25 µg of SN-38 decreased tumor size 3.5-fold. The therapy using the same doses of ¹³¹I-SN-38@lignin produced the most potent antitumor effect, with tumors being 6-fold smaller and having extensive intratumoral necrosis, all of it without signs of systemic toxicity. <b>Conclusions:</b> These results support the intratumoral delivery of lignin-based nanomaterial carrying radioisotopes and camptothecins for effective multimodal anticancer therapy.