Removing the Obstacle of Dye‐Sensitized Upconversion Luminescence in Aqueous Phase to Achieve High‐Contrast Deep Imaging In Vivo

Abstract

Although upconversion nanoparticles (UCNPs) have drawn increasing attention for their unique photophysical characteristics, they suffer from a bottleneck of low luminescence efficiency due to the poor absorption coefficient of Ln 3+ . Dye sensitization has provided thousands-fold enhancement of upconversion luminescence (UCL) in organic solvents because of the remarkably improved light absorption ability, but the sensitization of UCL in aqueous phase is only less than 20 folds by far, with unknown restrictive factors. Herein, the aggregation-caused quenching (ACQ) of dyes is revealed as the most important reason limiting dye sensitization in aqueous phase, and the problem is circumvented through delicately modulating the physical properties of dyes and their assembly manner with UCNPs. By further alleviating energy back transfer (EBT) from Ln 3+ to dyes, more than 600-fold enhancement of UCL is achieved in aqueous phase. The as-obtained dyes modified UCNPs show good biocompatibility and high signal contrast when applied for deep in vivo imaging.suitable for biological applications including bioimaging, biosensing, drug delivery, phototherapy, and so on. [3] However, due to the parity-forbidden nature of the 4f-4f electronic transitions of lanthanide ions, UCNPs suffer from poor light absorption [4] and accordingly extremely low luminescence efficiency and faint brightness, which impairs their performance in practical applications.In a pioneering work of 2012, Hummelen et al. put forward a dye-sensitization strategy to improve UCL intensity in organic solvent. Different from direct absorption of the excitation light by lanthanide ions, heptamethine cyanine with a much larger absorption cross section was employed as an antenna to absorb the energy of photons and transferred its excited-state energy to Ln 3+ ions through a resonance energy transfer pathway. [5] Owing to the dramatically enhanced light absorption ability, thousands-fold enhancement of UCL in organic phase has been achieved through the dye-sensitization process. [6] Considering the requirements of biological applications, efforts have also been devoted to the sensitization of UCL in aqueous phase. [7] Unfortunately, the sensitization efficiency in aqueous phase is badly restricted. In the past few years, although various structures and composition of UCNPs have been tried, this embarrassing situation changes very slowly. [8] Up to now, the highest enhancement factor of dye sensitization of UCL reported in aqueous phase was only 17-fold. [7a] This means that in a biological aqueous environment, the dye-sensitization strategy is not yet able to provide a solution to the bottleneck of UCL brightness. More importantly, the key factors restricting dye sensitization in aqueous phase are unclear so far.In this work, by delicately modulating the properties of dyes as well as their assembly manner with UCNPs, we discovered the factors that decide the sensitization efficiency. In previous dye-sensitized UCL systems in aqueous phase, dyes were assembled wi...

Luminescent nano‐bioprobes based on NIR dye/lanthanide nanoparticle composites

“…[7,15,17,41,46,[50][51][52]60,61] In vivo toxicity of NIR dye/LnNP nanoprobes has also been evaluated by hematology analysis, blood biochemical assay, and histological analysis on 7 or 15 days after intravenous injection of the nanoprobes into the nude mice. [54,[62][63][64] All the results showed no inflammatory response, nor any tissue injury in the treated mice as compared to the control group. In contrast, Pb/Cd-based QDs probes have Pb 2+ /Cd 2+ -induced cytotoxic effect and influence the hematopoiesis through oxidative stress.…”

“…ACQ effect of NIR dyes on the surface of LnNP is the most important factor limiting the sensitization efficiency. [54] In NIR dye/LnNP nanocomposites, the amount of NIR dye should be optimized to enhance the overall absorption with enough dyes and avoid the undesired self-quenching. Encapsulation by an amphiphilic polymer can provide a local hydropho-bic environment in aqueous solution, which is often used to reduce the degree of dye aggregation and increase the optimal concentration of NIR dye in the system.…”

“…[7] Liu and co-workers found that the distribution of NIR dye may also affect the aggregation degree. [54] Despite the protection of the same amphiphilic polymer, NIR dye Car-Cl with carboxyl groups tended to tightly bond on the surface of UCNP while another dye Alk-Cl with long hydrophobic alkyl moieties could freely spread in a hydrophobic layer (Figure 6A). It was estimated that the distance of adjacent Alk-Cl was close to Car-Cl (8.7 vs. 7.6 nm) at a low concentration of 1 nmol/mg but was twice that of Car-Cl (4.8 vs. 2.4 nm) at 10 nmol/mg.…”

Conjugate and non-conjugate controls of a sensitizer to enhance dye-sensitized upconversion luminescence

“…During the coordination of dyes with UCNPs, a high percentage of aggregated dyes are yielded on the nanoparticle surface owing to the aromatic p-conjugation plane and electrically charged head groups of cyanine dyes. [29][30][31][32] In particular, H-aggregation is high undesirable, resulting in strong fluorescence quenching effect to reduce the optimum number of dyes on the UCNP surface. Liu et al revealed that the aggregationcaused quenching of dyes is the most important reason limiting dye-sensitized upconversion.…”

Y2O3:Yb3+, Tm3+/ZnO composite with a heterojunction structure and upconversion function for the photocatalytic degradation of organic dyes

“…Based on the potential to achieve efficient solar energy utilization and good redox effects by combining UPT and photocatalytic materials, [29][30][31][32][33][34] in this study, Y 2 O 3 was co-doped with Tm 3+ and Yb 3+ to form an activator-sensitizer system (Y 2 O 3 :Yb 3+ , Tm 3+ ) using a sol-gel method. The effect of the Tm 3+ and Yb 3+ doping amount on the photoconversion performance of the UCNPs was then analyzed, and the photoconversion mechanism was evaluated.…”