Biomimetic nanoprodrugs from fatty acid modified camptothecin and albumin for enhanced pharmacotherapy

Design of nanovectors inspired by nature is a short cut to improve the efficacy and bioavailability of chemotherapeutic agents, while reduce the toxicity. In this work, strongly hydrophobic camptothecin (CPT) was modified with different chain length of fatty acid (C4, C9 and C18) to synthesize CPT4C, CPT9C and CPT18C, respectively. CPT4C, CPT9C and CPT18C could complex with human serum albumin (HSA) readily to prepare CPT4C-HSA, CPT9C-HSA and CPT18C-HSA nanoagents. In vitro MTT assays demonstrated CPT18C-HSA possessed the highest cell killing capacity, due to the elevated cellular uptake that resulted from albumin-mediated transportation. In vivo tumor inhibition experiments verified that CPT18C-HSA had the most remarkable antitumor efficiency with distinctly lowered physiological toxicity. It could be used in large doses without obvious side effects. We believe this albumin-mediated transportation mode has great potential for efficient delivery of hydrophobic and/or physiologically unstable drugs.