Dynamic Biostability, Biodistribution, and Toxicity of l/d-Peptide-Based Supramolecular Nanofibers

Citations Over TimeTop 11% of 2015 papers

Abstract

Self-assembling peptide nanofibers (including naturally L-amino acid-based and unnaturally D-amino acid-based ones) have been widely utilized in biomedical research. However, there has been no systematic study on their in vivo stability, distribution, and toxicity. Herein we systematically study the in vivo dynamic biostability, biodistribution, and toxicity of supramolecular nanofibers formed by Nap-GFFYGRGD (L-amino acid-based, L-fibers) and Nap-G(D)F(D)F(D)YGRGD (D-amino acid-based, D-fibers), respectively. The D-fibers have better in vitro and in vivo biostabilities than L-fibers. It is found that D-fibers keep a good integrity in plasma during 24 h, while half of l-fibers are digested upon incubation in plasma for 6 h. The biodistributions of L- and D-fibers are also studied using the iodine-125 radiolabeling technique. The results reveal that L-fibers mainly accumulate in stomach, whereas d-fibers preferentially distribute in liver. Successive administrations of both L- and D-fibers with the dose of 30 mg/kg/dose cause no significant inflammation, liver and kidney function damages, immune reaction, and dysfunction of hematopoietic system. This study will provide fundamental guidelines for utilization of self-assembling peptide-based supramolecular nanomaterials in biomedical applications, such as drug delivery, bioimaging, and regenerative medicine.

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