High-resolution 3D photopolymerization assisted by upconversion nanoparticles for rapid prototyping applications

Chen Z., Oprych D., Xie C., Kutahya C., Wu S., Strehmel B.

Upconversion nanoparticles (UCNPs) sensitized photolytitic cleavage of the blue/UV photoinitiator bis(4-methoxybenzoyl) diethyl germanium (1). 1 initiated radical photopolymerization in combination with NaYF4:TmYb@NaYF4 UCNPs. A 974 nm NIR laser served as excitation source to generate blue and UV light. In addition, a metal free photo-ATRP system comprising (i-propyl) thioxanthone (ITX), N,N,N′,N′′,N′′-pentamethyldiethylenetriamine (PMDETA) and -bromo(i-butyl) ethylester (-BrBuEt)) was used instead of 1. This resulted in a significant smaller polydispersity compared to the UCNP/1 system. Control of polymerization was successfully proved by chain extension showing control of chain termination. For the first time, we demonstrated photolytic formation of acidic cations in such NIR UCNP-systems comprising an ITX/iodonium photoinitiator for sensitized generation of acidic cations. In addition, 1 also resulted in crosslinking of 1,6-hexanediol diacrylate (HDDA) in combination with UCNP and NIR-laser excitation. UV filter materials such as TiO2 do not significantly interfere crosslinking.

Mironova K.E., Khochenkov D.A., Generalova A.N., Rocheva V.V., Sholina N.V., Nechaev A.V., Semchishen V.A., Deyev S.M., Zvyagin A.V., Khaydukov E.V.

Here we demonstrate that direct exposure of the cancer tissue to phototoxic ultraviolet radiation generated by NIR-photoexcited UCNPs enabled successful PDT.

Generalova A.N., Chichkov B.N., Khaydukov E.V.

Lanthanide-doped upconversion nanoparticles (UCNPs) have recently attracted great attention in theranostics due to their exceptional optical and physicochemical properties, which enable the design of a novel UCNP-based nanoplatform for luminescent imaging, temperature mapping, sensing, and therapy. In addition, UCNPs are considered to be ideal building blocks for development of multimodal probes for cells and whole body imaging, exploiting simple variation of host matrix, dopant ions, and surface chemistry. Modalities responsible for magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET)/single-photon emission computed tomography (SPECT) are embedded in a single UC nanocrystal, providing integrating effect over any modality alone in terms of the efficiency and sensitivity for clinical innovative diagnosis through multimodal bioimaging. In particular, we demonstrate applications of UCNPs as a new nanoplatform for optical and multimodal cancer imaging in vitro and in vivo and extend discussions to delivery of UCNP-based therapeutic agents for photodynamic and photothermal cancer treatments.

Savelyev A.G., Bardakova K.N., Khaydukov E.V., Generalova A.N., Popov V.K., Chichkov B.N., Semchishen V.A.

Hyaluronic acid and poly(ethylene glycol) derivatives attract considerable attention as precursors for tissue engineering. In this paper photocuring of biocompatible hyaluronic acid-glycidyl methacrylate (HAGM) and poly(ethylene glycol) diacrylate (PEG-DA) aqueous solutions, using flavin mononucleotide (FMN) as an endogenous photoinitiator, has been studied. The required threshold concentrations of initial macromolecules in water for the strengthening (increase of the Young’s modulus) of irradiated hydrogels have been determined as 57 wt% for 2D cross-linking of PEG-DA compositions and 16 wt% for 3D cross-linking of HAGM compositions. These concentrations are in a good agreement with correspondent values derived from the percolation theory for 2D and 3D lattices. It has been demonstrated that cross-linking proceeds predominantly by the radical mechanism and does not require co-initiators. Hydrogel scaffolds with specific and predetermined architectonics for biocompatibility and biomechanical studies have been produced by photopolymerizable micromolding.

Green K.K., Wirth J., Lim S.F.

We showed that the anisotropic disk shape of nanoplasmonic upconverting nanoparticles (NP-UCNPs) creates changes in fluorescence intensity during rotational motion. We determined the orientation by a three-fold change in fluorescence intensity. We further found that the luminescence intensity was strongly dependent on the particle orientation and on polarization of the excitation light. The luminescence intensity showed a three-fold difference between flat and on-edge orientations. The intensity also varied sinusoidally with the polarization of the incident light, with an Imax/Imin ratio of up to 2.02. Both the orientation dependence and Imax/Imin are dependent on the presence of a gold shell on the UCNP. Because the fluorescence depends on the NP’s orientation, the rotational motion of biomolecules coupled to the NP can be detected. Finally, we tracked the real-time rotational motion of a single NP-UCNP in solution between slide and coverslip with diffusivity up to 10−2 μm2s−1.

Darani M.K., Bastani S., Ghahari M., Kardar P., Mohajerani E.

Inventing a new light source for overcoming the disadvantages of conventional radiation curing technology is essential. Upconversion particles capable of emitting photon span from ultraviolet to NIR region of electromagnetic spectrum under excitation of NIR laser, could play the role of a light source within the formulation. Different amount of these upconversion particles were introduced to TMPTA monomer in order to survey their curing ability. The curing process was performed under various NIR laser intensities. The monomer to polymer conversion was studied using FT-IR and real-time FT-IR analysis. Increasing the filler content leads to better curing of the composite. Furthermore, the feasibility of curing TMPTMA containing camphorquinone as photoinitiator, by the blue upconversion emission was studied. Besides, the ability of these particles as UV and blue source cooperation in dual curing was observed. Increasing the photo-initiator and upconversion particles concentration resulted in higher double bond conversion. Increasing the laser intensity, by enhancing the upconversion emissions leads to better monomer to polymer conversion. The new source passed the inducing of dual curing process.

Alyatkin S., Asharchuk I., Khaydukov K., Nechaev A., Lebedev O., Vainer Y., Semchishen V., Khaydukov E.

The mechanism of upconversion at the nanoscale is still under discussion. In this paper, we report on the experimental results of anti-Stokes luminescence kinetics in the upconversion nanoparticles of β-NaYF4: 20%Yb3+; 0.6%Tm3+. The parameters of the luminescence kinetics were found to be unambiguously dependent on the number of excitation quanta n, which are necessary for certain transitions between the energy states of thulium ions. The observed correlation has been explained by means of the long-lasting energy migration between the ytterbium ions. The spread in time between the luminescent maxima of the corresponding thulium transitions not only shows the nonlinear character of upconversion, but also reveals the time scale of energy migration as well. From these, we derive that the conventional Förster formalism applied to the estimation of energy transfer efficiency in UCNP-fluorophore pairs can provide misleading results.

Ding C., Wang J., Zhang W., Pan X., Zhang Z., Zhang W., Zhu J., Zhu X.

The use of a 980 nm light providing deep penetration power and high compatibility for weak bonds shows potential for bio-related applications.

Khaydukov E.V., Mironova K.E., Semchishen V.A., Generalova A.N., Nechaev A.V., Khochenkov D.A., Stepanova E.V., Lebedev O.I., Zvyagin A.V., Deyev S.M., Panchenko V.Y.

Riboflavin (Rf) is a vitamin and endogenous photosensitizer capable to generate reactive oxygen species (ROS) under UV-blue irradiation and kill cancer cells, which are characterized by the enhanced uptake of Rf. We confirmed its phototoxicity on human breast adenocarcinoma cells SK-BR-3 preincubated with 30-μM Rf and irradiated with ultraviolet light, and proved that such Rf concentrations (60 μM) are attainable in vivo in tumour site by systemic intravascular injection. In order to extend the Rf photosensitization depth in cancer tissue to 6 mm in depth, we purpose-designed core/shell upconversion nanoparticles (UCNPs, NaYF4:Yb3+:Tm3+/NaYF4) capable to convert 2% of the deeply-penetrating excitation at 975 nm to ultraviolet-blue power. This power was expended to photosensitise Rf and kill SK-BR-3 cells preincubated with UCNPs and Rf, where the UCNP-Rf energy transfer was photon-mediated with ~14% Förster process contribution. SK-BR-3 xenograft regression in mice was observed for 50 days, following the Rf-UCNPs peritumoural injection and near-infrared light photodynamic treatment of the lesions.

Chen M., Zhong M., Johnson J.A.

The use of light to mediate controlled radical polymerization has emerged as a powerful strategy for rational polymer synthesis and advanced materials fabrication. This review provides a comprehensive survey of photocontrolled, living radical polymerizations (photo-CRPs). From the perspective of mechanism, all known photo-CRPs are divided into either (1) intramolecular photochemical processes or (2) photoredox processes. Within these mechanistic regimes, a large number of methods are summarized and further classified into subcategories based on the specific reagents, catalysts, etc., involved. To provide a clear understanding of each subcategory, reaction mechanisms are discussed. In addition, applications of photo-CRP reported so far, which include surface fabrication, particle preparation, photoresponsive gel design, and continuous flow technology, are summarized. We hope this review will not only provide informative knowledge to researchers in this field but also stimulate new ideas and applications to further advance photocontrolled reactions.

Liu R., Chen H., Li Z., Shi F., Liu X.

More than 10 centimeters of photopolymerization depth is obtained using upconversion nanoparticles as internal lamps.

Nadort A., Zhao J., Goldys E.M.

Upconversion photoluminescence is a nonlinear effect where multiple lower energy excitation photons produce higher energy emission photons. This fundamentally interesting process has many applications in biomedical imaging, light source and display technology, and solar energy harvesting. In this review we discuss the underlying physical principles and their modelling using rate equations. We discuss how the understanding of photophysical processes enabled a strategic influence over the optical properties of upconversion especially in rationally designed materials. We subsequently present an overview of recent experimental strategies to control and optimize the optical properties of upconversion nanoparticles, focussing on their emission spectral properties and brightness.

Hodak J., Chen Z., Wu S., Etchenique R.

Upconverting nanoparticles (UCNPs) present emission in the visible region upon irradiation with NIR light through a multiphoton mechanism. However, the long characteristic time of their emission has prevented the use of this kind of entities as multiphoton probes. We present a study on the use of erbium-containing UCNPs under pulsed excitation, showing that both the power density and the duration of the excitation pulse are key factors to understand the emission behavior. By adjusting power and excitation rate, we can obtain typical multiphoton z-axis focal exclusive excitation. These findings open the possibility of using UCNPs as probes for controlled localization of uncaging and imaging with multiphoton z-axis sectioning. We show that this can be achieved even at power densities several orders of magnitude lower than traditional multiphoton microscopies.

Méndez-Ramos J., Ruiz-Morales J.C., Acosta-Mora P., Khaidukov N.M.

Cost-effective luminescent 3D-printing technology approach through infrared-laser-induced photon up-conversion in rare-earth-doped materials for “laser-writing” of luminescent 3D printed structures and envisioned applications in nano-photolithography.

Villanueva-Delgado P., Krämer K.W., Valiente R.

The design of upconversion phosphors with higher quantum yield requires a deeper understanding of the detailed energy transfer and upconversion processes between active ions inside the material. Rate equations can model those processes by describing the populations of the energy levels of the ions as a function of time. However, this model presents some drawbacks: energy migration is assumed to be infinitely fast, it does not determine the detailed interaction mechanism (multipolar or exchange), and it only provides the macroscopic averaged parameters of interaction. Hence, a rate equation model with the same parameters cannot correctly predict the time evolution of upconverted emission and power dependence under a wide range of concentrations of active ions. We present a model that combines information about the host material lattice, the concentration of active ions, and a microscopic rate equation system. The extent of energy migration is correctly taken into account because the energy transfer process...

Bektas C.K., Luo J., Conley B., Le K.N., Lee K.

Solodov A.N., Zimin K., Gataullina R.M., Zagidullin A.A., Leontyev A.V., Shmelev A.G., Nurtdinova L.A., Nikiforov V.G., Khasanov O.K., Amirova L.M., Tayurskii D.A., Ivanova A., Kiiamov A., Zharkov D.K.

Koshelev A.V., Korshunov V.M., Artemov V.V., Arkharova N.A., Taydakov I.V., Seyed Dorraji M.S., Karimov D.N.

Savelyev A.G., Sochilina A.V., Babayeva G., Nikolaeva M.E., Kuziaeva V.I., Prostyakova A., Sergeev I., Gorin D., Khaydukov E., Generalova A.N., Akasov R.

Photocrosslinkable hydrogels based on hyaluronic acid are promising biomaterials highly demanded in tissue engineering. Typically, hydrogels are photocured under the action of UV or blue light strongly absorbed by biotissues,...

Zhigar'kov V.S., Yusupov V.I., Khaydukov E.V.

Hu Y., Luo Z., Bao Y.

Hammecke H., Fritzler D., Vashistha N., Jin P., Dietzek-Ivanšić B., Wang C.

AbstractThe triplet excited state lifetime of a photosensitizer is an essential parameter for diffusion‐controlled energy‐ and electron‐transfer, which occurs usually in a competitive manner to the intrinsic decay of a triplet excited state. Here we show the decisive role of luminescence lifetime in the triplet excited state reactivity toward energy‐ and electron transfer. Anchoring two phenyl anthracene chromophores to a ruthenium(II) polypyridyl complex (RuII ref) leads to a RuII triad with a luminescence lifetime above 100 μs, which is more than 40 times longer than that of the prototypical complex. The obtained RuII triad sensitizes energy transfer to anthracene‐based annihilators more efficiently than RuII ref and enables red‐to‐blue photon upconversion with a pseudo anti‐Stokes shift of 0.94 eV and a moderate upconversion efficiency near 1 % in aerated solution. Particularly, RuII triad allows rapid photoredox catalytic polymerizations of acrylate and acrylamide monomers under aerobic condition with red light, which are kinetically hindered for RuII ref. Our work shows that excited state lifetime of a photosensitizer governs the dynamics of the excited state reactions, which seems an overlooked but important aspect for photochemistry.

Yaemsunthorn K., Macyk W., Ortyl J.

Kandeloos A.J., Bastani S., Ghahari M., Jalili M., Lalevée J.

AbstractNIR‐induced upconversion‐assisted photopolymerization has gained growing attention in the past two decades because of its numerous advantages over conventional UV/visible photopolymerization and two‐photon polymerization processes. However, research in this area is still in its early stages. To extend the practical application of NIR‐induced radiation curing, it is essential to optimize the factors affecting the photopolymerization reactions. Researchers have been constantly trying to improve these factors to tune the photo‐physical characteristics (luminescence intensity and color) of upconversion particles (UCPs), enhance curing depths and degree of double bond conversion (DC), and investigate the application of UCPs in emerging fields. In this review, first, a brief discussion of the upconversion mechanisms and upconversion efficiency is provided. Then, a detailed discussion of the factors influencing the upconversion‐assisted photopolymerization comprising UCP nature and characteristics, UCP content, presence of fillers/pigments/additives, laser intensity, photoinitiator content, and maximum absorption wavelength of photoinitiator is provided, and recent progress in improving these factors is presented. Finally, the advantages and drawbacks of the UC‐initiated polymerization are discussed, and perspectives for future directions are suggested.Highlights NIR‐induced upconversion‐assisted photopolymerization garners growing interest. Influential factors in upconversion‐assisted photopolymerization are thoroughly discussed. The recent progress on improving these factors and the future directions are provided.

Chansoria P., Rizzo R., Rütsche D., Liu H., Delrot P., Zenobi-Wong M.

Zhigarkov V.S., Yusupov V.I., Khaydukov E.V.

A method of the transfer of NaYF4:Yb3+Tm3+/NaYF4 upconversion core/shell nanoparticles with an average size of 30 nm via laser-induced forward transfer is proposed. The method provides a high spatial resolution by creating a “sandwich” structure on the donor substrate: for reliable fixation, nanoparticles are located between gold layers 50 and 20 nm thick. The transfer of upconversion nanoparticles is implemented by focusing nanosecond laser radiation into a 30-μm-diameter spot and at optimal pulse energies of 8.5–25 μJ. It has been shown that, despite large temperature, $$\Delta T > 1000{\kern 1pt} $$ K, and pressure, $$\Delta P > 150{\kern 1pt} $$ MPa, fluctuations upconversion nanoparticles fully retain their photoluminescent characteristics.

Zhakeyev A., Devanathan R., Marques-Hueso J.

Traditional photopolymer-based 3D printing methods require sequential printing of thin layers, due to short penetration depths of UV or blue light sources used by these techniques. In contrast, upconversion 3D printing circumvents the layer-by-layer limitation by taking advantage of upconversion luminescence processes and the high penetration depths offered by near-infrared (NIR) lasers, allowing for selective crosslinking of voxels at any depth or position within the resin container. The implementation of this technique required the construction of a 3D printer with the ability of focusing the laser on any point of the space. For this, a low-cost fused filament fabrication (FFF) printer was modified by incorporating a 980 nm laser and laser control circuit. The total cost of the parts required for modification was £180. With enhanced penetration depths up to 5.8 cm, this method also allows for printing inside or through existing 3D printed parts. This opens doors for restoration of broken items, in situ bioprinting, 3D-circuitry, and notably, 3D printing inside cavities of a different material, illustrating numerous opportunities for practical applications.

Huang L., Han G.

Photon upconversion is a method for harnessing high-energy excited states from low-energy photons. Such photons, particularly in the red and near-infrared wavelength ranges, can penetrate tissue deeply and undergo less competitive absorption in coloured reaction media, enhancing the efficiency of large-scale reactions and in vivo phototherapy. Among various upconversion methodologies, the organic-based triplet–triplet annihilation upconversion (TTA-UC) stands out — demonstrating high upconversion efficiencies, requiring low excitation power densities and featuring tunable absorption and emission wavelengths. These factors contribute to improved photochemical reactions for fields such as photoredox catalysis, photoactivation, 3D printing and immunotherapy. In this Review, we explore concepts and design principles of organic TTA-UC-mediated photochemical reactions, highlighting notable advancements in the field, as well as identify challenges and propose potential solutions. This Review sheds light on the potential of organic TTA-UC to advance beyond the traditional photochemical reactions and paves the way for research in various fields and clinical applications. Organic-based triplet–triplet annihilation upconversion-mediated photochemical reactions utilize low-energy photons to obtain high-energy excited states leading to notable advancements in photoredox catalysis, photoactivation, 3D printing and immunotherapy. Classifications, design principles, challenges and possible solutions are discussed in this Review.

Pan J., Skripka A., Lee C., Qi X., Pham A.L., Woods J.J., Abergel R.J., Schuck P.J., Cohen B.E., Chan E.M.

Kiiamov A., Solodov A., Zimin K., Ramilya G.M., Zagidullin A.A., Dmitrii Z.K., Andrey L.V., Artemii S.G., Larisa N.A., Nikiforov V.G., Amirova L., Amirov R., Oleg K.K., Tayurskii D.A., Anna I.G.