Bioinspired nanocarriers designed to enhance intracellular delivery of biotherapeutics

The biotechnology and pharmaceutical industries have developed a wide variety of potential therapeutics based on the molecules of biology: DNA, RNA and proteins. While these therapeutics have tremendous potential, effectively formulating and delivering them has also been a widely recognized challenge. A variety of viruses and toxins have evolved multi-functional biopolymer complexes to solve this problem by directing uptake and enhancing biomolecular transport to the cytoplasm from the low pH endosomal compartment. Here, we have designed and synthesized bio-inspired, pH-responsive polymeric carriers that mimic the multifunctional design of biology. These nanocarriers target and direct cellular uptake, as well as enhance cytosolic delivery by disrupting endosomal membranes in pH-dependent fashion. We show that the encrypted polymeric carriers significantly enhance the delivery oligonucleotides and peptides to the cytoplasm of cultured hepatocytes and macrophages, demonstrating the potential of this approach to therapeutic and vaccine development.