Remarkable NIR Enhancement of Multifunctional Nanoprobes for In Vivo Trimodal Bioimaging and Upconversion Optical/T2‐Weighted MRI‐Guided Small Tumor Diagnosis

Effective nanoprobes and contrast agents are urgently sought for early‐stage cancer diagnosis. Upconversion nanoparticles (UCNPs) are considerable alternatives for bioimaging, cancer diagnosis, and therapy. Yb³⁺/Tm³⁺ co‐doping brings both emission and excitation wavelengths into the near‐infrared (NIR) region, which is known as “optical transmission window” and ideally suitable for bioimaging. Here, NIR emission intensity is remarkably enhanced by 113 times with the increase of Yb³⁺ concentration from 20% to 98% in polyethylene glycol (PEG) modified NaYF₄:Yb³⁺/Tm³⁺ UCNPs. PEG‐UCNPs‐5 (98% Yb³⁺) can act as excellent nanoprobes and contrast agents for trimodal upconversion (UC) optical/CT/T₂‐weighted magnetic resonance imaging (MRI). In addition, the enhanced detection of lung in vivo long‐lasting tracking, as well as possible clearance mechanism and excretion routes of PEG‐UCNPs‐5 have been demonstrated. More significantly, a small tumor down to 4 mm is detected in vivo via intravenous injection of these nanoprobes under both UC optical and T₂‐weighted MRI modalities. PEG‐UCNPs‐5 can emerge as bioprobes for multi‐modal bioimaging, disease diagnosis, and therapy, especially the early‐stage tumor diagnosis.     

Atomic‐Level Passivation of Individual Upconversion Nanocrystal for Single Particle Microscopic Imaging

Lanthanide‐doped upconversion nanoparticles (UCNPs) have significant applications for single‐molecule probes and high‐resolution display. However, one of their major hurdles is the weak luminescence, and this remains a grand challenge to achieve at the single‐particle level. Here, 484‐fold luminescence enhancement in LuF₃:Yb³⁺, Er³⁺ rhombic flake UCNPs is achieved, thanks to the Yb³⁺‐mediated local photothermal effect, and their original morphology, size, and good dispersibility are well preserved. These data show that the surface atomic structure of UCNPs as well as transfer from amorphous to ordered crystal structure is modulated by making use of the local photothermal conversion that is generated by the directional absorption of 980 nm light by Yb³⁺ ions. The confocal luminescence images obtained by super‐resolution stimulated emission depletion also show the great enhancement of individual LuF₃:Yb³⁺, Er³⁺ nanoparticles; the high signal‐to‐noise ratio images indicate that the laser treatment technology opens the door for single particle imaging and practical application.     

Positive and Negative Lattice Shielding Effects Co‐existing in Gd (III) Ion Doped Bifunctional Upconversion Nanoprobes

Gadolinium (Gd) doped upconversion nanoparticles (UCNPs) have been well documented as T₁‐MR and fluorescent imaging agents. However, the performance of Gd³⁺ ions located differently in the crystal lattice still remains debatable. Here, a well‐designed model was built based on a seed‐mediated growth technique to systematically probe the longitudinal relaxivity of Gd³⁺ ions within the crystal lattice and at the surface of UCNPs. We found, for the first time, a nearly 100% loss of relaxivity of Gd³⁺ ions buried deeply within crystal lattices (> 4 nm), which we named a “negative lattice shielding effect” (n‐LSE) as compared to the “positive lattice shielding effect” (p‐LSE) for the enhanced upconversion fluorescent intensity. As‐observed n‐LSE was further found to be shell thickness dependent. By suppressing the n‐LSE as far as possible, we optimized the UCNPs' structure design and achieved the highest r₁ value (6.18 mM^?1s^?1 per Gd³⁺ ion) among previously reported counterparts. The potential bimodal imaging application both in vitro and in vivo of as‐designed nano‐probes was also demonstrated. This study clears the debate over the role of bulk and surface Gd³⁺ ions in MRI contrast imaging and paves the way for modulation of other Gd‐doped nanostructures for highly efficient T₁‐MR and upconversion fluorescent bimodal imaging.     

Effects of Phonon Confinement on Anomalous Thermalization,Energy Transfer,and Upconversion in Ln3+‐Doped Gd2O3 Nanotubes

There is a growing interest in understanding how size‐dependent quantum confinement affects the photoluminescence efficiency, excited‐state dynamics, energy‐transfer and thermalization phenomena in nanophosphors. For lanthanide (Ln³⁺)‐doped nanocrystals, despite the localized 4f states, confinement effects are induced mostly via electron–phonon interactions. In particular, the anomalous thermalization reported so far for a handful of Ln³⁺‐doped nanocrystals has been rationalized by the absence of low‐frequency phonon modes. This nanoconfinement may further impact on the Ln³⁺ luminescence dynamics, such as phonon‐assisted energy transfer or upconversion processes. Here, intriguing and unprecedented anomalous thermalization in Gd₂O₃:Eu³⁺ and Gd₂O₃:Yb³⁺,Er³⁺ nanotubes, exhibiting up to one order of magnitude larger than previously reported for similar materials, is reported. This anomalous thermalization induces unexpected energy transfer from Eu³⁺ C₂ to S₆ crystallographic sites, at 11 K, and ²H_11/2 → ⁴I_15/2 Er³⁺ upconversion emission; it is interpreted on the basis of the discretization of the phonon density of states, easily tuned by varying the annealing temperature (923–1123 K) in the synthesis procedure, and/or the Ln³⁺ concentration (0.16–6.60%).     

Solution‐Processable Near‐Infrared–Responsive Composite of Perovskite Nanowires and Photon‐Upconversion Nanoparticles

Organolead halide perovskites (OHPs) have shown unprecedented potentials in optoelectronics. However, the inherent large bandgap has restrained its working wavelength within 280–800 nm, while light at other regions, e.g., near‐infrared (NIR), may cause drastic thermal heating effect that goes against the duration of OHP devices, if not properly exploited. Herein, a solution processable and large‐scale synthesis of multifunctional OHP composites containing lanthanide‐doped upconversion nanoparticles (UCNPs) is reported. Upon NIR illumination, the upconverted photons from UCNPs at 520–550 nm can be efficiently absorbed by closely surrounded OHP nanowires (NWs) and photocurrent is subsequently generated. The narrow full width at half maximum of the absorption of rare earth ions (Yb³⁺ and Er³⁺) has ensured high‐selective NIR response. Lifetime characterizations have suggested that Förster resonance energy transfer with an efficiency of 28.5% should be responsible for the direct energy transfer from UCNPs to OHP NWs. The fabricated proof‐of‐concept device has showcased perfect response to NIR light at 980 and 1532 nm, which has paved new avenues for applications of such composites in remote control, distance measurement, and stealth materials.     

Er3+ Sensitized Photon Upconversion Nanocrystals

Lanthanide doped upconversion nanocrystals, showing bright future in diverse fields, are typically excited by ≈700–1000 nm light when Nd³⁺ and Yb³⁺ are used as sensitizers. Thus far, extending the excitation range of upconversion nanocrystals is still a formidable challenge. Herein, a new type of upconversion nanocrystals is reported, using Er³⁺ ions as sensitizers, which can be excited by 1532 nm light located in the second near‐infrared biological window. Through Er³⁺ sensitization, upconversion emission from a series of activators, including Nd³⁺, Ho³⁺, Eu³⁺, and Tm³⁺, is obtained and can be modulated by Yb³⁺ codoping. In addition, Er³⁺ sensitized photon upconversion of Ho³⁺ and Tm³⁺ can be further enhanced by shell coating. It is found that Er³⁺ sensitized upconversion processes are mainly dependent on the energy transfer between Er³⁺ ions and activators. Considering the demonstration of anticounterfeiting by using this newly designed nanocrystal, it is anticipated that these results can bring more opportunities to upconversion nanomaterials in other aspects, ranging from lasing to super resolution imaging.     

Highly Emissive Nd3+‐Sensitized Multilayered Upconversion Nanoparticles for Efficient 795 nm Operated Photodynamic Therapy

Photodynamic therapy (PDT) is a noninvasive and site‐specific therapeutic technique for the clinical treatment of various of superficial diseases. In order to tuning the operation wavelength and improve the tissue penetration of PDT, rare‐earth doped upconversion nanoparticles (UCNPs) with strong anti‐stokes emission are introduced in PDT recently. However, the conventional Yb³⁺‐sensitized UCNPs are excited at 980 nm which is overlapped with the absorption of water, thus resulting in strong overheating effect. Herein, a convenient but effective design to obtain highly emissive 795 nm excited Nd³⁺‐sensitized UCNPs (NaYF₄:Yb,Er@NaYF₄:Yb_0.1Nd_0.4@NaYF₄) is reported, which provides about six times enhanced upconversion luminescence, comparing with traditional UCNPs (NaYF₄:Yb,Er@NaYF₄). A colloidal stable and non‐leaking PDT nanoplatform is fabricated later through a highly PEGylated mesoporous silica layer with covalently linked photosensitizer (Rose Bengal derivative). With as‐prepared Nd³⁺‐sensitized UCNPs, the nanoplatform can produce singlet oxygen more effective than traditional UCNPs. Significant higher penetration depth and lower overheating are demonstrated as well. All these features make as‐prepared nanocomposites excellent platform for PDT treatment. In addition, the nanoplatform with uniform size, high surface area, and excellent colloidal stability can be extended for other biomedical applications, such as imaging probes, biosensors, and drug delivery vehicles.     

Anomalous Raman Scattering of Colloidal Yb3+,Er3+ Codoped NaYF4 Nanophosphors and Dynamic Probing of the Upconversion Luminescence

Size‐dependent Raman spectra of the hexagonal (β)‐phase Yb³⁺,Er³⁺ codoped NaYF₄ nanophosphors and dynamic probing of the upconversion luminescence (UCL) are reported. Raman scattering results show the normal red shifts of Raman peaks but anomalous line narrowing with decreasing the particle sizes. The phonon confinement effects are believed to be dominated by the surface vibrational energies in affecting UCL. Dynamic decay data are then applied to quantitatively verify the surface effects and size‐dependent UCL. Dynamic probing is shown to be an efficient tool to both qualitatively and quantitatively characterize the upconversion nanophorphors (UCNPs) that have no “quantum efficiency.” The findings are relevant to the engineering of the nanostructures of the UCNPs for the applications of the bioimaging and photodynamic therapy.     

A New Single 808 nm NIR Light‐Induced Imaging‐Guided Multifunctional Cancer Therapy Platform

The NIR light‐induced imaging‐guided cancer therapy is a promising route in the targeting cancer therapy field. However, up to now, the existing single‐modality light‐induced imaging effects are not enough to meet the higher diagnosis requirement. Thus, the multifunctional cancer therapy platform with multimode light‐induced imaging effects is highly desirable. In this work, captopril stabilized‐Au nanoclusters Au₂₅(Capt)₁₈?(Au₂₅) are assembled into the mesoporous silica shell coating outside of Nd³⁺‐sensitized upconversion nanoparticles (UCNPs) for the first time. The newly formed Au₂₅ shell exhibits considerable photothermal effects, bringing about the photothermal imaging and photoacoustic imaging properties, which couple with the upconversion luminescence imaging. More importantly, the three light‐induced imaging effects can be simultaneously achieved by exciting with a single NIR light (808 nm), which is also the triggering factor for the photothermal and photodynamic cancer therapy. Besides, the nanoparticles can also present the magnetic resonance and computer tomography imaging effects due to the Gd³⁺ and Yb³⁺ ions in the UCNPs. Furthermore, due to the photodynamic and the photothermal effects, the nanoparticles possess efficient in vivo tumor growth inhibition under the single irradiation of 808 nm light. The multifunctional cancer therapy platform with multimode imaging effects realizes a true sense of light‐induced imaging‐guided cancer therapy.     

Effectively Utilizing NIR Light Using Direct Electron Injection from Up‐Conversion Nanoparticles to the TiO2 Photoanode in Dye‐Sensitized Solar Cells

TiO₂/NaYF₄:Yb³⁺,Er³⁺ nano‐heterostructures are prepared in situ on the TiO₂ photoanode of dye‐sensitized solar cells (DSCs). Transmission electron microscopy (TEM) and high‐resolution (HR)‐TEM confirm the formation of TiO₂/NaYF₄:Yb³⁺,Er³⁺ nano‐heterostructures. The up‐converted fluorescence spectrum of the photoanode containing the nano‐heterostructure confirms electron injection from NaYF₄:Yb³⁺,Er³⁺ to the condution band (CB) of TiO₂. When using a photoanode containing the nano‐heterostructure in a DSC, the overall efficiency (η) of the device is 17% higher than that of a device without the up‐conversion nanoparticles (UCNPs) and 13% higher than that of a device containing mixed TiO₂ and UCNPs. Nano‐heterostructures of TiO₂/NaYF₄:Yb³⁺,Tm³⁺ and TiO₂/NaYF₄:Yb³⁺,Ho³⁺ can also be prepared in situ on TiO₂ photoanodes. The overall efficiency of the device containing TiO₂/NaYF₄:Yb³⁺,Ho³⁺ nano‐heterostructures is 15% higher than the control device without UCNPs. When nano‐heterostructures of TiO₂/NaYF₄:Yb³⁺,Tm³⁺ are used, the open‐circuit voltage (V_oc) and the short‐circuit current density (J_sc) are all slightly decreased. The effect of the different UCNPs results from the different energy levels of Er³⁺, Tm³⁺, and Ho³⁺. These results demonstrate that utilizing the UCNPs with the apporpriate energy levels can lead to effective electron injection from the UCNPs to the CB of TiO₂, effectively improving the photocurrent and overall efficiency of DSCs while using NIR light.     

Single Ho3+‐Doped Upconversion Nanoparticles for High‐Performance T2‐Weighted Brain Tumor Diagnosis and MR/UCL/CT Multimodal Imaging

Multimodal bio‐imaging has attracted great attention for early and accurate diagnosis of tumors, which, however, suffers from the intractable issues such as complicated multi‐step syntheses for composite nanostructures and interferences among different modalities like fluorescence quenching by MRI contrast agents (e.g., magnetic iron oxide NPs). Herein, the first example of T₂‐weighted MR imaging of Ho³⁺‐doped upconversion nanoparticles (UCNPs) is presented, which, very attractively, could also be simultaneously used for upconversion luminesence (UCL) and CT imaging, thus enabling high performance multi‐modal MRI/UCL/CT imagings in single UCNPs. The new finding of T₂‐MRI contrast enhancement by integrated sensitizer (Yb³⁺) and activator (Ho³⁺) in UCNPs favors accurate MR diagnosis of brain tumor and provides a new strategy for acquiring T₂‐MRI/optical imaging without fluorescence quenching. Unlike other multi‐phased composite nanostructures for multimodality imaging, this Ho³⁺‐doped UCNPs are featured with simplicity of synthesis and highly efficient multimodal MRI/UCL/CT imaging without fluorescence quenching, thus simplify nanostructure and probe preparation and enable win–win multimodality imaging.     

Morphological Evolution and Magnetic Property of Rare‐Earth‐Doped Hematite Nanoparticles: Promising Contrast Agents for T1‐Weighted Magnetic Resonance Imaging

A series of uniform rare‐earth‐doped hematite (α‐Fe₂O₃) nanoparticles are synthesized by a facile hydrothermal strategy. In a typical case of gadolinium (Gd)‐doped α‐Fe₂O₃, the morphology and chemical composition can be readily tailored by tuning the initial proportion of Gd³⁺/Fe³⁺ sources. As a result, the products are observed to be stretched into more elongated shapes with an increasing dopant ratio. As a benefit of such an elongated morphological feature and Gd³⁺ ions of larger effective magnetic moment than Fe³⁺, the doped product with the highest ratio of Gd³⁺ at 5.7% shows abnormal ferromagnetic features with a remnant magnetization of 0.605 emu g^?1 and a coercivity value of 430 Oe at 4 K. Density of states calculations also reveal the increase of total magnetic moment induced by Gd³⁺ dopant in α‐Fe₂O₃ hosts, as well as possible change of magnetic arrangement. As‐synthesized Gd‐doped α‐Fe₂O₃ nanoparticles are probed as contrast agents for T1‐weighted magnetic resonance imaging, achieving a remarkable enhancement effect for both in vitro and in vivo tests.     

Rare earth doped TiO2-CdS and TiO2-CdS composites with improvement of photocatalytic hydrogen evolution under visible light irradiation

In this paper, we report the obtention of a series of rare earth doped composite Pt/RE/TiO₂-CdS (RE=La³⁺, Eu³⁺, Er³⁺, Gd³⁺) and TiO₂-CdS photocatalysts prepared by a simple mechanical mixed method. The photocatalysts properties were studied by means of ultraviolet-visible spectroscopy, photoluminiscence spectra, X-ray diffraction, transmission electron microscopy, specific surface areas and the electrochemistry method. Photocatalytic hydrogen evolution using Na₂S/Na₂SO₃ as electron donor was investigated under visible-light (λ≥420 nm) irradiation. The rare earth doping enhances the activities of Pt/RE/TiO₂-CdS samples (with 1.0 wt% deposited Pt). Under optimum conditions, the activities of La³⁺, Eu³⁺, Er³⁺, Gd³⁺ doped composite Pt/RE/TiO₂-CdS increase by 62.0%, 40.4%, 34.7% and 30.0% respectively, when compared to that of Pt/TiO₂-CdS, due to the prevention of electron–hole recombination and the flat-band potential of the conduction of TiO₂ shifting negatively by the doping.     

Cypate‐Conjugated Porous Upconversion Nanocomposites for Programmed Delivery of Heat Shock Protein 70 Small Interfering RNA for Gene Silencing and Photothermal Ablation

Synergistic therapy is an accepted method of enhancing the efficacy of cancer therapies. In this study, cypate‐conjugated porous NaLuF₄ doped with Yb³⁺, Er³⁺, and Gd³⁺ is synthesized and its potential for upconversion luminescence/magnetic resonance dual‐modality molecular imaging for guiding oncotherapy is tested. Loading cypate‐conjugated upconversion nanoparticles (UCNP‐cy) with small interfering RNA gene against heat shock protein 70 (UCNP‐cy‐siRNA) enhances the cell damage. UCNP‐cy‐siRNA exhibits remarkable antitumor efficacy in vivo as a result of the synergistic effects of gene silencing and photothermal therapy, with low drug dose and minimal side effects. This result thus provides an explicit strategy for developing next‐generation multifunctional nanoplatforms for multimodal imaging‐guided synergistic oncotherapy.     

Gd3+‐Ion‐Doped Upconversion Nanoprobes: Relaxivity Mechanism Probing and Sensitivity Optimization

Paramagnetic gadolinium (Gd‐III)‐ion‐doped upconversion nanoparticles (UCNPs) are attractive optical‐magnetic molecule imaging probes and are a highly promising nanoplatform for future theranostic nanomedicine design. However, the related relaxivity mechanism of this contrast agent is still not well understood and no significant breakthrough in relaxivity enhancement has been achieved. Here, the origin and optimization of both the longitudinal (r₁) and transverse (r₂) relaxivities are investigated using models of water soluble core@shell structured Gd³⁺‐doped UCNPs. The longitudinal relaxivity enhancement of the nanoprobe is demonstrated to be co‐contributed by inner‐and outer‐sphere mechanisms for ligand‐free probes, and mainly by outer‐sphere mechanism for silica‐shielded probes. The origin of the transverse relaxivity is inferred to be mainly from an outer‐sphere mechanism regardless of surface‐coating, but with the r₂ values highly related to the surface‐state. Key factors that influence the observed relaxivities and r₂/r₁ ratios are investigated in detail and found to be dependent on the thickness of the NaGdF₄ interlayer and the related surface modifications. A two orders of magnitude (105‐fold) enhancement in r₁ relaxivity and 18‐fold smaller r₂/r₁ ratio compared to the first reported values are achieved, providing a new perspective for magnetic resonance (MR) sensitivity optimization and multimodality biological imaging using Gd³⁺‐doped UCNPs.     

Down/Up Conversion in Ln3+‐Doped YF3 Nanocrystals

Nanocrystalline Ln³⁺‐doped YF₃ phosphors have been synthesized via a facile sonochemistry‐assisted hydrothermal route. YF₃ nanoparticles are demonstrated to be a good host material for different lanthanides. Varying the dopants leads to different optical properties. In particular, the feasibility of inducing red, green, and especially blue emission in the Yb³⁺/Er³⁺ co‐doped YF₃ sample by up‐conversion excitation in the near‐infrared region is demonstrated. Such unusually strong 411 nm blue up‐conversion emission has seldom been reported in other Yb³⁺/Er³⁺‐doped systems. The up‐conversion mechanisms have been analyzed.     

Up‐Conversion Luminescent and Porous NaYF4:Yb3+, Er3+@SiO2 Nanocomposite Fibers for Anti‐Cancer Drug Delivery and Cell Imaging

Up‐conversion (UC) luminescent and porous NaYF₄:Yb³⁺, Er³⁺@SiO₂ nanocomposite fibers are prepared by electrospinning process. The biocompatibility test on L929 fibrolast cells reveals low cytotoxicity of the fibers. The obtained fibers can be used as anti‐cancer drug delivery host carriers for investigation of the drug storage/release properties. Doxorubicin hydrochloride (DOX), a typical anticancer drug, is introduced into NaYF₄:Yb³⁺, Er³⁺@SiO₂ nanocomposite fibers (denoted as DOX‐NaYF₄:Yb³⁺, Er³⁺@SiO₂). The release properties of the drug carrier system are examined and the in vitro cytotoxicity and cell uptake behavior of these NaYF₄:Yb³⁺, Er³⁺@SiO₂ for HeLa cells are evaluated. The release of DOX from NaYF₄:Yb³⁺, Er³⁺@SiO₂ exhibits sustained, pH‐sensitive release patterns and the DOX‐NaYF₄:Yb³⁺, Er³⁺@SiO₂ show similar cytotoxicity as the free DOX on HeLa cells. Confocal microscopy observations show that the composites can be effectively taken up by HeLa cells. Furthermore, the fibers show near‐infrared UC luminescence and are successfully applied in bioimaging of HeLa cells. The results indicate the promise of using NaYF₄:Yb³⁺, Er³⁺@SiO₂ nanocomposite fibers as multi‐functional drug carriers for drug delivery and cell imaging.     

Spectral properties and energy transfer in Er3+/Yb3+ co-doped LiYF4 crystal

Laser crystals of LiYF4 (LYF) singly doped with Er3+ in 2.0% and co-doped with Er3+/Yb3+ in about 2.0%/1.0% molar fraction in the raw composition are grown by a vertical Bridgman method. X-ray diffraction (XRD), absorption spectra, fluorescence spectra and decay curves are measured to investigate the structural and luminescent properties of the crystals. Compared with the Er3+ singly doped sample, obviously enhanced emission at 1.5 μm wavelength and green and red up-conversion emissions from Er3+/Yb3+ co-doped crystal are observed under the excitation of 980 nm laser diode. Meanwhile, the emission at 2.7 μm wavelength from Er3+ singly doped crystal is reduced. The fluorescence decay time ranging from 18.60 ms for Er3+ singly doped crystal to 23.01 ms for Er3+/Yb3+ co-doped crystal depends on the ionic concentration. The luminescent mechanisms for the Er3+/Yb3+ co-doped crystals are analyzed, and the possible energy transfer processes from Yb3+ to Er3+ are proposed.     

Novel Sol–Gel Nano‐Glass–Ceramics Comprising Ln3+‐Doped YF3 Nanocrystals: Structure and High Efficient UV Up‐Conversion

Transparent glass‐ceramics containing Ln³⁺‐doped YF₃ nanocrystals are successfully obtained under adequate thermal treatment of precursor sol–gel glasses for the first time, to the best of our knowledge. Precipitation of YF₃ nanocrystals is confirmed by X‐ray diffraction and high‐resolution transmission electron microscopy images. An exhaustive structural analysis is carried out using Eu³⁺ and Sm³⁺ as probe ions of the final local environment in the nano‐structured glass–ceramic. Noticeable changes in luminescence spectra, related to relative intensity and Stark structure of band components, along with remarkably different lifetime values, allow us to discern between ions residing in precipitated YF₃ nanocrystals and those remaining in a glassy environment. A large fraction of optically active ions is efficiently partitioned into nanocrystals of small size, around 11 nm. Moreover, bright and efficient up‐conversion, including very intense high‐energy emissions in the UV range, due to 4‐ and 5‐infrared photon processes, are achieved in Yb³⁺–Tm³⁺ co‐doped samples. Up‐conversion mechanisms are analysed in depth by means of intensity dependence on sensitiser Yb³⁺ concentration and pump power.     

Pegylated Composite Nanoparticles Containing Upconverting Phosphors and meso‐Tetraphenyl porphine (TPP) for Photodynamic Therapy

The utilization of upconverting nanophosphors (UCNP) for photodynamic therapy (PDT) has gained significant interests due to its ability to convert deep‐penetrating near‐infra red (NIR) light (i.e., 978 nm) to visible light. Previous attempts to co‐localize UCNPs with photosensitizers suffer from low photo­sensitizer loading and problems with nanoparticle aggregation. Here, the preparation of a novel composite nanoparticle formulation comprising 100 nm β?NaYF₄:Yb³⁺,Er³⁺ UCNPs, and meso‐tetraphenyl porphine (TPP) photo­sensitizer, stabilized by biocompatible poly(ethylene glycol‐block‐(dl )lactic acid) block copolymers (PEG‐b‐PLA) is presented. A photosensitizer loading of 10 wt% with respect to UCNP crystal was achieved via the Flash NanoPrecipitation (FNP) process. A sterically stabilizing PEG layer on the composite nanoparticle surface prevents nanoparticle aggregation and ensures nanoparticle stability in water, PBS buffer, and culture medium containing serum proteins, resulting in nanoparticle suitable for in vivo applications. Based on in vitro studies utilizing HeLa cervical cancer cell lines, the composite nanoparticles are shown to exhibit low dark toxicity and efficient cancer cell‐killing activity upon NIR excitation. Exposure with 134 W cm^?2 of 978 nm light for 45 min resulted in 75% HeLa cell death. This is the first quantification of the cell‐killing capabilities of the UCNP/TPP composite nanoparticles formulated for photodynamic therapy.