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Abstract Natural originated materials have been well-studied over the past several decades owing to their higher biocompatibility compared to the traditional polymers. Peptides, consisting of amino acids, are among the most popular programmable building blocks, which is becoming a growing interest in nanobiotechnology. Structures assembled using those biomimetic peptides allow the exploration of chemical sequences beyond those been routinely used in biology. In this review, we discussed the most recent experimental discoveries on the peptide-based assembled nanostructures and their potential application at the cellular level such as drug delivery. In particular, we explored the fundamental principles of peptide self-assembly and the most recent development in improving their interactions with biological systems. We believe that as the fundamental knowledge of the peptide assemblies evolves, the more sophisticated and versatile nanostructures can be built, with promising biomedical applications. 

The self-assembly of nanostructures from conjugates of elastin-like peptides and collagen-like peptides (ELP-CLP) has been studied as means to produce thermoresponsive, collagen-binding drug delivery vehicles. Motivated by our previous work in which ELP-CLP conjugates successfully self-assembled into vesicles and platelet-like nanostructures, here, we extend our library of ELP-CLP bioconjugates to a series of tryptophan/phenylalanine-containing ELPs and GPO-based CLPs [W 2 F x - b -(GPO) y ] with various domain lengths to determine the impact of these modifications on the thermoresponsiveness and morphology. The lower transition temperature of the conjugates with longer ELP or CLP domains enables the formation of well-defined nanoparticles near physiological temperature. Moreover, the morphological transition from vesicles to platelet-like nanostructures occurred when the ratio of the lengths of ELP/CLP decreased. Given the previously demonstrated ability of many ELP-CLP bioconjugates to bind to both hydrophobic drugs and collagen-containing materials, our results suggest new opportunities for designing specific thermoresponsive nanostructures for targeted biological applications. 

Collagen-targeting strategies have proven to be an effective method for targeting drugs to pathological tissues for treatment of disease. The use of collagen-like peptides for controlling the assembly of drug delivery vehicles, as well as their integration into collagen-containing matrices, offers significant advantages for tuning the morphologies of assembled structures, their thermoresponsiveness, and the loading and release of both small-molecule and macro-molecular cargo. In this contribution, we summarize the design and development of collagen-peptide-based drug delivery systems introduced by the Kiick group and detail the expansion of our understanding and the application of these unique molecules through collaborations with experts in computational simulations (Jayaraman), osteoarthritis (Price), and gene delivery (Sullivan). Kiick was inducted as a Fellow of the National Academy of Inventors in 2019 and was to deliver an address describing the innovations of her research. Given the cancellation of the NAI Annual Meeting as a result of coronavirus travel restrictions, her work based on collagen-peptide-mediated assembly is instead summarized in this contribution.