Branched amphiphilic peptide capsules: Cellular uptake and retention of encapsulated solutes

• BAPCs are branched amphiphilic peptide capsules that self-assemble into bilayer delimited spheres.
• BAPCs are taken up by cells and accumulate near the perinuclear region; where they persist without degradation.
• BAPCs do not yield their cargo and can encapsulate proteins up to 13.7 kDa.
• BAPCs can encapsulate radionuclides such as 225Ac and retain up to 95% of their encapsulate over a period of 7 days.
• BAPCs demonstrate potential as a novel delivery system for targeted alpha particle therapy.

Branched amphiphilic peptide capsules (BAPCs) are peptide nano-spheres comprised of equimolar proportions of two branched peptide sequences bis(FLIVI)-K-KKKK and bis(FLIVIGSII)-K-KKKK that self-assemble to form bilayer delimited capsules. In two recent publications we described the lipid analogous characteristics of our BAPCs, examined their initial assembly, mode of fusion, solute encapsulation, and resizing and delineated their capability to be maintained at a specific size by storing them at 4 °C. In this report we describe the stability, size limitations of encapsulation, cellular localization, retention and, bio-distribution of the BAPCs in vivo. The ability of our constructs to retain alpha particle emitting radionuclides without any apparent leakage and their persistence in the peri-nuclear region of the cell for extended periods of time, coupled with their ease of preparation and potential tune-ability, makes them attractive as biocompatible carriers for targeted cancer therapy using particle emitting radioisotopes. This article is part of a Special Issue entitled: Interfacially Active Peptides and Proteins. Guest Editors: William C. Wimley and Kalina Hristova.

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