Kim, Kyuri Wi, Ji Hun Baek, Dongjun Kim, Young Yong Yeom, Bongjun Lee, Sanghee Kim, Yongju 2025-09-17T01:32:02Z 2025-09-17T01:32:02Z 2025-09-16 2025-09 1530-6984 https://pubs.kist.re.kr/handle/201004/153156 Sorafenib, a clinically approved multityrosine kinase inhibitor, exhibits poor aqueous solubility, which limits its bioavailability and therapeutic efficacy. In this study, we introduce a solvent-directed self-assembly strategy to modulate the nanostructure of sorafenib without the use of external carriers or complex formulation techniques. In pure water, sorafenib forms large lamellar aggregates, whereas in 30% methanol-water mixtures, it self-assembles into uniform spherical particles approximately 450 nm in diameter. These spherical particles exhibit markedly enhanced cellular uptake (similar to 80%) and cytotoxicity (up to 60% at 40 mu M) in HepG2 liver cancer cells compared to the poorly active lamellar form. In vivo pharmacokinetic analysis further reveals faster absorption, biphasic plasma distribution, and prolonged circulation of the spherical particle forms. These findings demonstrate that solvent-driven nanostructure modulation can serve as a simple yet effective strategy to improve the solubility-limited pharmacological performance of small-molecule drugs like sorafenib. English American Chemical Society Solvent-Directed Self-Assembly of Sorafenib into Spherical Particles for Enhanced Anticancer Efficacy Article 10.1021/acs.nanolett.5c03250 1 Nano Letters, v.25, no.37, pp.13819 - 13826 Nano Letters 25 37 13819 13826 N scie scopus 001566329500001 Chemistry, Multidisciplinary Chemistry, Physical Nanoscience & Nanotechnology Materials Science, Multidisciplinary Physics, Applied Physics, Condensed Matter Chemistry Science & Technology - Other Topics Materials Science Physics Article DRUG-DELIVERY PHARMACOKINETICS MICELLES TUMOR Spherical particles Nanostructures Self-assembly Solubility enhancement Sorafenib