Supramolecular Nanostructures Formed by Anticancer Drug Assembly

Abstract

We report here a supramolecular strategy to directly assemble the small molecular hydrophobic anticancer drug camptothecin (CPT) into discrete, stable, well-defined nanostructures with a high and quantitative drug loading. Depending on the number of CPTs in the molecular design, the resulting nanostructures can be either nanofibers or nanotubes, and have a fixed CPT loading content ranging from 23% to 38%. We found that formation of nanostructures provides protection for both the CPT drug and the biodegradable linker from the external environment and thus offers a mechanism for controlled release of CPT. Under tumor-relevant conditions, these drug nanostructures can release the bioactive form of CPT and show in vitro efficacy against a number of cancer cell lines. This strategy can be extended to construct nanostructures of other types of anticancer drugs, and thus presents new opportunities for the development of self-delivering drugs for cancer therapeutics.

Peptide Self-Assembled Nanostructures for Drug Delivery Applications

“…The amphiphilic drugs are composed of a tau protein derived peptide conjugated with a hydrophobic anticancer drug camptothecin. These materials could be self-assembled into fibril structures through hydrophobic interactions and intermolecular hydrogen bonding [110].…”

Self-Assembly of Peptide Bioconjugates: Selected Recent Research Highlights

“…Cui et al have investigated the formation of fibrils or nanotubes by a short β-sheet peptide derived from the Tau protein linked via a short octyl spacer to the anticancer drug camptothecin. 31 These nanostructures were shown to have anti-tumor activity against a number of cancer cell lines. Following a similar concept, camptothecin has been conjugated to a short yeast prion peptide (Sup35) along with charged C terminal dipeptide units (two lysine or two glutamic acid residues).…”

Nanosized Camptothecin Conjugates for Single and Combined Drug Delivery

“…Cheetham etc conjugated one to four camptothecin molecules to a β-sheet-forming peptide sequence derived from the Tau protein through the reducible disulfylbutyrate (buSS) linker (41). The drug loading of camptothecin can be precisely controlled as of 23%, 31% and 38% and electron microscopy revealed the self-assembly of these drug amphiphiles into either nano filamentous or nanotubes structures in water depending on the number of camptothecin attached on the Tau peptide.…”