ArticleACS omega2026
Exatecan-Loaded HSA Nanoparticles for Sustained Release and Enhanced Cancer Treatment.
Article in ACS omega, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Authors and funding
3 authors.
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Abstract
Exatecan, a potent topoisomerase 1 inhibitor and a potent anticancer agent, is derived from naturally occurring camptothecin. Its clinical development has been halted due to dose-limiting toxicities and a shorter plasma half-life in humans. To overcome these challenges, we synthesized a novel human serum albumin nanoparticle (Exa-HSA-NPs) for selective cancer therapy. The Exa-HSA-NPs exhibited a uniform spherical morphology with an average hydrodynamic diameter of 147 nm, zeta potential of -24 mV, and a very low polydispersity index (PDI < 0.1). STEM-EDS mapping confirmed homogeneous distribution of exatecan within the albumin medium. In vitro release kinetics demonstrated pH-responsive, sustained drug release for up to 9 days, with faster release in acidic (tumor-like) conditions. Molecular docking of exatecan with HSA revealed the formation of a stable complex stabilized by hydrophobic interactions and hydrogen bonding. Exa-HSA-NPs displayed potent cytotoxicity in oral cancer (AW13516) and lung cancer (A549) cells, with significantly reduced toxicity in non-cancerous HEK293T cells. Cellular uptake analysis revealed preferential NPs internalization in cancer cells (70% in AW13516, 63% in A549) compared with normal cells (27%), consistent with gp60 and SPARC-mediated albumin uptake mechanisms. Apoptosis assays confirmed selective induction of cancer cell death with minimal impact on normal cells. The Exa-HSA-NPs exhibited excellent biodegradability and hemocompatibility, indicating favorable safety and potential for clinical translation. Overall, Exa-HSA-NPs offer a promising strategy for the sustained, selective tumor delivery of exatecan, with an improved therapeutic index and reduced systemic toxicity.
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Registered trials
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