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Abstract Drug nanoaggregates are particles that can deleteriously cause false positive results during drug screening efforts, but alternatively, they may be used to improve pharmacokinetics when developed for drug delivery purposes. The structural features of molecules that drive nanoaggregate formation remain elusive, however, and the prediction of intracellular aggregation and rational design of nanoaggregate-based carriers are still challenging. We investigate nanoaggregate self-assembly mechanisms using small molecule fragments to identify the critical molecular forces that contribute to self-assembly. We find that aromatic groups and hydrogen bond acceptors/donors are essential for nanoaggregate formation, suggesting that both π-π stacking and hydrogen bonding are drivers of nanoaggregation. We apply structure-assembly-relationship analysis to the drug sorafenib and discover that nanoaggregate formation can be predicted entirely using drug fragment substructures. We also find that drug nanoaggregates are stabilized in an amorphous core-shell structure. These findings demonstrate that rational design can address intracellular aggregation and pharmacologic/delivery challenges in conventional and fragment-based drug development processes. 

Autophagy is a cellular process with important functions that drive neurodegenerative diseases and cancers. Lysosomal hyperacidification is a hallmark of autophagy. Lysosomal pH is currently measured by fluorescent probes in cell culture, but existing methods do not allow for quantitative, transient or in vivo measurements. In the present study, we developed near-infrared optical nanosensors using organic color centers (covalent sp3 defects on carbon nanotubes) to measure autophagy-mediated endolysosomal hyperacidification in live cells and in vivo. The nanosensors localize to the lysosomes, where the emission band shifts in response to local pH, enabling spatial, dynamic and quantitative mapping of subtle changes in lysosomal pH. Using the sensor, we observed cellular and intratumoral hyperacidification on administration of mTORC1 and V-ATPase modulators, revealing that lysosomal acidification mirrors the dynamics of S6K dephosphorylation and LC3B lipidation while diverging from p62 degradation. This sensor enables the transient and in vivo monitoring of the autophagy–lysosomal pathway. 

Abstract Chirality purification of single-walled carbon nanotubes (SWCNTs) is desirable for applications in many fields, but general utility is currently hampered by low throughput. We discovered a method to obtain single-chirality SWCNT enrichment by the aqueous two-phase extraction (ATPE) method in a single step. To achieve appropriate resolution, a biphasic system of non-ionic tri-block copolymer surfactant is varied with an ionic surfactant. A nearly-monochiral fraction of SWCNTs can then be harvested from the top phase. We also found, via high-throughput, near-infrared excitation-emission photoluminescence spectroscopy, that the parameter space of ATPE can be mapped to probe the mechanics of the separation process. Finally, we found that optimized conditions can be used for sorting of SWCNTs wrapped with ssDNA as well. Elimination of the need for surfactant exchange and simplicity of the separation process make the approach promising for high-yield generation of purified single-chirality SWCNT preparations.