Intracellular localization of nanoparticle dimers by chirality reversal

• Published in: Nature communications 2017-11, Vol.8 (1), p.1847-10, Article 1847
• Main Authors: Sun, Maozhong, Xu, Liguang, Bahng, Joong Hwan, Kuang, Hua, Alben, Silas, Kotov, Nicholas A., Xu, Chuanlai
• Format: Article
• Language: English
• Subjects: 631/1647/350; 639/624/399/354; 639/925/928/1065; 639/925/930/527/873; Biomedical materials; Cancer; Cell-Penetrating Peptides - chemistry; Cervical cancer; Cervix; Chirality; Circular Dichroism; Circular polarization; Cytosol; Deoxyribonucleic acid; Diagnostic systems; Dichroism; Dimerization; Dimers; DNA; DNA - chemistry; Drug Delivery Systems; Electron Microscope Tomography - methods; Gold - chemistry; HeLa Cells; Humanities and Social Sciences; Humans; Internalization; Intracellular; Localization; Mammalian cells; multidisciplinary; Nanoparticles; Nanoparticles - administration & dosage; Nanoparticles - analysis; Nanoparticles - chemistry; Nanotubes - chemistry; Photochemotherapy - methods; Photodynamic therapy; Photons; Photosensitizing Agents - administration & dosage; Protoporphyrins - administration & dosage; Reactive oxygen species; Science; Science (multidisciplinary); Spectrophotometry, Ultraviolet; Spectroscopy; Transport; Twisting movement
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-017-01337-2

The intra- and extracellular positioning of plasmonic nanoparticles (NPs) can dramatically alter their curative/diagnostic abilities and medical outcomes. However, the inability of common spectroscopic identifiers to register the events of transmembrane transport denies their intracellular vs. extracellular localization even for cell cultures. Here we show that the chiroptical activity of DNA-bridged NP dimers allows one to follow the process of internalization of the particles by the mammalian cells and to distinguish their extra- vs intra-cellular localizations by real-time spectroscopy in ensemble. Circular dichroism peaks in the visible range change from negative to positive during transmembrane transport. The chirality reversal is associated with a spontaneous twisting motion around the DNA bridge caused by the large change in electrostatic repulsion between NPs when the dimers move from interstitial fluid to cytosol. This finding opens the door for spectroscopic targeting of plasmonic nanodrugs and quantitative assessment of nanoscale interactions. The efficacy of dichroic targeting of chiral nanostructures for biomedical applications is exemplified here as photodynamic therapy of malignancies. The efficacy of cervical cancer cell elimination was drastically increased when circular polarization of incident photons matched to the preferential absorption of dimers localized inside the cancer cells, which is associated with the increased generation of reactive oxygen species and their preferential intracellular localization. The ability to spectroscopically pinpoint whether nanoparticles are located inside or outside of cells represents an overarching need in biology and medicine. Here, the authors show that the chirality of DNA-bridged particle dimers reverses when they cross the cell membrane, providing a real-time chiroptical signature of their intra- or extracellular location.