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Responsive core-shell DNA particles trigger lipid-membrane disruption and bacteria entrapment.

ABSTRACT: Biology has evolved a variety of agents capable of permeabilizing and disrupting lipid membranes, from amyloid aggregates, to antimicrobial peptides, to venom compounds. While often associated with disease or toxicity, these agents are also central to many biosensing and therapeutic technologies. Here, we introduce a class of synthetic, DNA-based particles capable of disrupting lipid membranes. The particles have finely programmable size, and self-assemble from all-DNA and cholesterol-DNA nanostructures, the latter forming a membrane-adhesive core and the former a protective hydrophilic corona. We show that the corona can be selectively displaced with a molecular cue, exposing the 'sticky' core. Unprotected particles adhere to synthetic lipid vesicles, which in turn enhances membrane permeability and leads to vesicle collapse. Furthermore, particle-particle coalescence leads to the formation of gel-like DNA aggregates that envelop surviving vesicles. This response is reminiscent of pathogen immobilisation through immune cells secretion of DNA networks, as we demonstrate by trapping E. coli bacteria.

SUBMITTER: Walczak M

PROVIDER: S-EPMC8346484 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Recently, the functionalization of nanoparticles, either within themselves or on the outer surface and its application in medicine, turned out to be the ultimate goal of nanotechnology. By providing these nanoparticles with chemical functional groups, one can force the nanoparticles to target the markers of the particular diseases or to measure the quantity and distribution of various intracellular species. In this paper, we report our development of a pH-responsive nanocomposite based on lanthanide-doped upconverting nanoparticles (UCNPs). Through multiphoton absorption and energy migration between spatially separated Nd3+, Yb3+, and Tm3+ in a three-layered NaYF4 host coated with FITC (fluorescein-5-isothiocyanate), this nanocomposite can measure the pH with high sensitivity. The fundamental acidity measurement is based on the pH-dependent equilibrium of the bright and dark states of FITC. The tremendous advantages of this system, regarding the pH measurement, come from the fact that the versatility of UCNP-imaging can fully be exploited. This includes the fact that (a) the optical wavelengths for the sensitization (980 nm and/or 808 nm) and the emission bands (UV, visible) are well separated, (b) the spectral overlap between FITC (absorption) and Tm3+ (emission) is substantially high, (c) there is no background signal due to the near-infrared laser, and (d) the signals are consistent regardless of the fluctuations by monitoring the ratio of blue band with respect to the unaffected self-reference (red and near-infrared bands). Moreover, the double shell structure is obviously superior to the core-shell structure in that it enhances the spectral separation between the sensitizer and the emitter in the upconversion process, inhibiting any unnecessary contamination in the spectra. Finally, it is noteworthy that Yb3+ plays crucial roles as a sensitizer at 980 nm excitation and a bridge above which 808 nm excitation migrates from Nd3+ to Tm3+ via the Yb3+ excited state.

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Responsive core-shell DNA particles trigger lipid-membrane disruption and bacteria entrapment.

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