Biocompatible Peptide‐nanoparticle Constructs for Molecular Imaging and Therapy

Abstract

Our recent work on melittin delivery demonstrates that melittin tightly inserts into the perfluorocarbon (PFC) nanoparticles. Here, we hypothesize that altering the melittin sequence can convert melittin from a therapeutic agent to a cargo loading linker for PFC nanoparticles. Our results illustrate that mutated melittin, D1‐7 (Ac‐ VLTTGLPALISWIKRKRQQ‐NH2), reduces the melittin lytic activity by about 50‐fold (A). While it still insertes tightly into the PFC nanoparticles (Kd=0.4 μM) without affecting their integrity (B). We also show that the linker peptide, D1‐7, is capable of integrating cargos into PFC nanoparticles by a simple mixing step. As an example, VCAM‐1 targeted PFC nanoparticles are generated through this linker peptide. 2F2B cells, treated with the VCAM‐1 targeted PFC nanoparticles, co‐labeled with Alexa Fluor 488, manifest stronger fluorescent signals (C) than those, treated with non‐targeted ones (D). VCAM‐1 targeting dramatically increases cellular PFC nanoparticle delivery (E). Moreover, targeting efficacy is controllable by amount of peptide loading (F). We conclude that this linker peptide strategy provides extended flexibility for multiplexing targeting ligands and/or drug payloads, which can be selected from a stock of possible active agents, without the need of base nanoparticle reformulation to behoove personalized molecular imaging and therapy.