Tuning the Internal Compartmentation of Single‐Chain Nanoparticles as Fluorescent Contrast Agents

Abstract

Controlling the internal structures of single‐chain nanoparticles (SCNPs) is an important factor for their targeted chemical design and synthesis, especially in view of nanosized compartments presenting different local environments as a main feature to control functionality. We here design SCNPs bearing near‐infrared fluorescent dyes embedded in hydrophobic compartments for use as contrast agents in pump–probe photoacoustic (PA) imaging, displaying improved properties by the location of the dye in the hydrophobic particle core. Compartment formation is controlled via single‐chain collapse and subsequent crosslinking of an amphiphilic polymer using external crosslinkers in reaction media of adjustable polarity. Different SCNPs with hydrodynamic diameters of 6‐12 nm bearing adjustable label densities are synthesized. It is found that the specific conditions for single‐chain collapse have a major impact on the formation of the desired core–shell structure, in turn adjusting the internal nanocompartments together with the formation of excitonic dye couples, which in turn increase their fluorescence lifetime and PA signal generation. SCNPs with the dye molecules accumulate at the core also show a nonlinear PA response as a function of pulse energy—a property that can be exploited as a contrast mechanism in molecular PA tomography.

Thermoresponsive Reversible Unimer Micelles of Amphiphilic Fluorinated Copolymers

“…Therefore, the field has experienced remarkable growth in the last two decades. [ 4–6 ] Practical application of such artificial single‐chain nanostructures may be enormous, and several examples are already present in the scientific literature, especially in the fields of, but not limited to, catalytic nanoreactors, [ 7,8 ] nanoprobes, [ 9 ] environmental remediation, [ 10,11 ] vectors for contrast agents, [ 12–14 ] encapsulation and delivery carriers, [ 15–18 ] surfactants, [ 19,20 ] and anti(bio)fouling systems. [ 21 ]…”

“…Therefore, the field has experienced remarkable growth in the last two decades. [4][5][6] Practical application of such artificial single-chain nanostructures may be enormous, and several examples are already present in the scientific literature, especially in the fields of, but not limited to, catalytic nanoreactors, [7,8] nanoprobes, [9] environmental remediation, [10,11] vectors for contrast agents, [12][13][14] encapsulation and delivery carriers, [15][16][17][18] surfactants, [19,20] and anti(bio)fouling systems. [21] Recent advances in polymer chemistry resulted in considerable progress toward the synthesis of artificial polymers with reproducible self-folding ability via elective point folding methods and repeat unit folding routes.…”

Amphiphilic Fluorinated Unimer Micelles as Nanocarriers of Fluorescent Probes for Bioimaging

“…We propose a process for the production of fluorescent unimer micelles that is simple, and less chemically demanding, compared to the formation of fluorescent SCNPs by multistep intramolecular crosslink. 15,18,21,23,40 Then, we demonstrate the efficient permeation in sclera of the dye-loaded unimer micelles, allowing the direct visualization of the fluorescent probe in the whole tissue.…”

“…More generally, the work represents a proof of concept of the ability of self-folded unimer micelles to transport small hydrophobic molecules, avoiding covalent interactions, and with potential applications also in the fields of drug delivery, sensing, etc. We propose a process for the production of fluorescent unimer micelles that is simple, and less chemically demanding, compared to the formation of fluorescent SCNPs by multistep intramolecular crosslink. ,,,, Then, we demonstrate the efficient permeation in sclera of the dye-loaded unimer micelles, allowing the direct visualization of the fluorescent probe in the whole tissue.…”

Protein‐Inspired Control over Synthetic Polymer Folding for Structured Functional Nanoparticles in Water

“…A more recent addition to the repertoire of SCPN characterization is the use of continuous wave electron paramagnetic resonance (CW EPR). [191][192][193][194] Here, the attachment of a TEMPO spin label to the SCPN backbone can elucidate not only its compartmentalized nature, but also the effect of temperature on the mobility within the nanocompartments. In combination with Overhauser dynamic nuclear polarization, [191] information on the local water translational diffusion dynamics around the spin label can be gained.…”