Nanoparticles can improve drug pharmacokinetics, but low loading efficiencies can limit treatment efficacy. Drug-aggregation-based nanoparticles have demonstrated improved loadings of up to 90%, but few excipients facilitate efficient co-assembly. We investigated peptides as designer excipients because of their diverse chemical space and inherent biodegradability. We designed pentapeptide scaffolds to mimic the structure of known indocyanine excipients by modulating aromaticity, rigidity, and charge. We screened 184 formulations by using diverse drug cargoes. We found drug-peptide combinations that formed nanoparticles with up to 98% drug loading. Molecular dynamics simulations and mass spectrometry analysis demonstrated that tryptophan-drug interactions and solvent exposure of charged amino acid residues drove the formation of core-shell structures. Peptide-drug formulations containing the JAK2/FLT3 inhibitor lestaurtinib were investigated in acute myeloid leukemia models, resulting in enhanced anti-tumor efficacy. This work found that oligopeptides can be designed to efficiently co-assemble with therapeutic cargoes to result in high-loading nanoparticles that improve anti-tumor efficacy.

One of the major challenges in studying biological systems is the dearth of robust tools available to monitor dynamic biological processes in live cells and animals. For example, current techniques to measure autophagy are either ex vivo or involve conventional fluorophores/fluorescent proteins, which can be used for in vitro measurements but present problems in vivo. In this presentation, we show the development of optical nanosensors that non-invasively monitor autophagy-associated lysosomal pH changes. The sensor technology is based on quantum-defect-modified fluorescent carbon nanotubes, often called organic color centers (OCCs). OCC fluorescence is bright, photostable, and optically tunable by the chemical nature of the color center. We designed the OCC-nanosensors to be sensitive and selective to endolysosomal pH. Their unique chemical and photophysical properties enabled dynamic and quantitative measurements of lysosomal pH in live cells and in vivo. We will discuss how we utilize these capabilities to facilitate previously inaccessible mechanistic insights in the fields of cancer biology.

Organic color centers (OCC) are synthetic color-centers that are incorporated in single-wall carbon nanotubes by covalently attaching functional groups to the otherwise crystalline semiconductors. OCCs feature extraordinary traits that make these synthetic materials an ideal platform for the biochemical sensing applications. First, the OCC-induced fluorescence peak is extremely sensitive to the local microenvironment around the functional group that induced each OCC. Second, OCCs are molecularly tunable. Depending on the chemical nature of the functional group that induces each OCC, the fluorescence features can be systematically controlled. Based on the extraordinary chemical tunability and sensitivity of OCCs, we construct a perception-based sensing array that enables multiplexed sensing of disease biomarkers in biofluids. The sensing array consists of systematically designed OCC-receptor elements that non-specifically interact with a myriad of molecular species in biofluid. The diverse spectral responses of the sensor array, trained by machine learning, collectively determine the disease fingerprints.