ABSTRACT
Synergistic photodynamic therapy (PDT) with other therapeutic modalities can enhance the therapeutic efficacy of tumor treatment and reduce the adverse effects associated with drug leakage and off-target accumulation. However, shaping combined strategies for synergistic therapy remains challenging. Herein, we developed versatile hybrid liposomes self-assembled from Ce6-lipid conjugates and loaded with the chemo drug doxorubicin (DOX) and ferroptosis inducer Fe3O4 nanoparticles for synergistic PDT/chemo/ferroptosis therapy. Abundant ROS are generated by PDT upon 650 nm light irradiation, Fe3O4-mediated Fenton reaction, and DOX-induced apoptosis. Furthermore, amplifying oxidative stress in cancer cells to disrupt cellular redox homeostasis could accelerate tumor cell death through oxidative damage to lipids, proteins, and DNA. Overall, this work highlights liposome-based therapeutic nanoformulations, thus offering a breakthrough redox homeostasis-based synergistic PDT/chemo/ferroptosis therapy for lung cancer.
ABSTRACT
Developing high-efficiency nondoped blue organic light-emitting diodes (OLEDs) with high color purity and low-efficiency roll-off is vital for display and lighting applications. Herein, we developed two asymmetric D-π-A blue emitters, PIAnTP and PyIAnTP, in which triphenylene is first utilized as a functional acceptor. The relatively weak charge transfer (CT) properties, rigid molecular structures, and multiple supramolecular interactions in PIAnTP and PyIAnTP can significantly enhance the fluorescence efficiency and suppress the structural relaxations to obtain a narrowband blue emission. The photophysical experiments and theoretical simulations reveal that they both exhibit a typical hybridized local and charge-transfer (HLCT) excited state and achieve high external quantum efficiency (EQE) via a "hot exciton" channel. As a result, PIAnTP- and PyIAnTP-based nondoped devices realize blue emission at 456 and 464 nm, corresponding to CIE coordinates of (0.16, 0.14) and (0.16, 0.19), narrow full width at half-maximums of 52 and 60 nm, and the high EQEs of 8.36 and 8.69%, respectively. More importantly, the PIAnTP- and PyIAnTP-based nondoped devices show small EQE roll-offs of only 5.9 and 2.4% at 1000 cd m-2, respectively. These results signify an advance in designing a highly efficient blue emitter for nondoped OLEDs.
ABSTRACT
Periodontitis is a biofilm-related disease characterized by damage to the periodontal tissue and the development of systemic diseases. However, treatment of periodontitis remains unsatisfactory, especially with deep-tissue infections. This study describes rationally designed multifunctional photothermocatalytic agents for near-infrared-II light-mediated synergistic antibiofilm treatment, through modification of Lu-Bi2Te3 with Fe3O4 and poly(ethylene glycol)-b-poly(l-arginine) (PEG-b-PArg). Notably, 1064-nm laser irradiation led to photothermal/thermocatalytic effects, resulting in the synergistic generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and consequent damage to the biofilm. This treatment was based on the thermoelectric and photothermal conversion properties of Lu-Bi2Te3, the peroxidase-like catalytic capacity of Fe3O4, and the guanidinium polymer, PEG-b-PArg. Oxidative damage to biofilm was further enhanced by H2O2, resulting in the effective elimination of biofilm both in vitro and in vivo. These findings suggest that this synergistic therapeutic strategy is effective for the clinical treatment of periodontitis. STATEMENT OF SIGNIFICANCE: The current treatment for periodontitis involves time-consuming and labor-intensive clinical scaling of the teeth. The present study is the first to assess the efficacy of a photothermal catalyst for periodontitis treatment. This used near-infrared-II light at 1064 nm to induce oxidative damage in the biofilm, resulting in its degradation. The synergistic photothermal/thermoelectric effect produced deep tissue penetration and was well tolerated, and can kill the biofilm formed by periodontitis pathogens up to 5 orders of magnitude, effectively treating the biofilm-induced periodontitis.
Subject(s)
Hyperthermia, Induced , Periodontitis , Humans , Hydrogen Peroxide , Periodontitis/therapy , Phototherapy , Oxidative StressABSTRACT
Highly doped lanthanide luminescent nanoparticles exhibit unique optical properties, providing exciting opportunities for many ground-breaking applications, such as super-resolution microscopy, deep-tissue bioimaging, confidentiality, and anticounterfeiting. However, the concentration-quenching effect compromises their luminescence efficiency/brightness, hindering their wide range of applications. Herein, we developed a low-temperature suppression cross-relaxation strategy, which drastically enhanced upconversion luminescence (up to 2150-fold of green emission) in Er3+-rich nanosystems. The cryogenic field opens the energy transport channel of Er3+ multiphoton upconversion by further suppressing phonon-assisted cross-relaxation. Our results provide direct evidence for understanding the energy loss mechanism of photon upconversion, deepening a fundamental understanding of the upconversion process in highly doped nanosystems. Furthermore, it also suggests the potential applications of upconversion nanoparticles for extreme ambient-temperature detection and anticounterfeiting.
ABSTRACT
Lanthanide-doped upconversion nanoparticles (UCNPs) have attracted great attention in temperature sensing because of their widespread thermal quenching effect (TQE), a phenomenon in which luminescence intensity decreases as the temperature increases. However, enhancing the TQE of activated ions without changing the dopants or the host is still challenging. Herein, Yb3+ and Er3+ codoped UCNPs in a cubic CaGdF5 host were synthesized by a coprecipitation method for optical temperature sensing. Compared with the homogeneous shell (CaGdF5), those heterogeneous (CaF2) shelled UCNPs exhibited stronger upconversion luminescence (UCL) due to the significantly reduced multiphonon nonradiative relaxation. Further, we investigated the effects of homogeneous and heterogeneous shells on TQE. The relationship between the intensity ratio of the green emission bands of Er3+ ions (2H11/2 â 4I15/2 and 4S3/2 â 4I15/2) and temperature are obtained for these two core@shell UCNPs. The results demonstrated that the UCNPs with CaF2 shells are more sensitive to temperature in the 200-300 K. The maximum thermal sensitivity of CaGdF5:Yb,Er@CaF2 could reach 2.2% K-1 at 200 K. These results indicate that the heterogeneous core@shell UCNPs are promising for use as optical temperature sensors.
ABSTRACT
Fluorescence bioimaging based on rare-earth-doped nanocrystals (RENCs) in the shortwave infrared (SWIR, 1000-3000 nm) region has aroused intense interest due to deeper penetration depth and clarity. However, their downshifting emission rarely shows sufficient brightness beyond 1600 nm, especially in NIR-IIc. Here, we present a class of thulium (Tm) self-sensitized RENC fluorescence probes that exhibit bright downshifting luminescence at 1600-2100 nm (NIR-IIb/c) for in vivo bioimaging. An inert shell coating minimizes surface quenching and combines strong cross-relaxation, allowing LiTmF4@LiYF4 NPs to emit these intense downshifting emissions by absorbing NIR photons at 800 nm (large Stokes shift ~1000 nm with a absolute quantum yield of ~14.16%) or 1208 nm (NIR-IIin and NIR-IIout). Furthermore, doping with Er3+ for energy trapping achieves four-wavelength NIR irradiation and bright NIR-IIb/c emission. Our results show that Tm-based NPs, as NIR-IIb/c nanoprobes with high signal-to-background ratio and clarity, open new opportunities for future applications and translation into diverse fields.
Subject(s)
Metals, Rare Earth , Nanoparticles , Luminescence , Thulium , Metals, Rare Earth/chemistry , Nanoparticles/chemistry , PhotonsABSTRACT
Photodynamic therapy (PDT) efficiency is directly affected by the reactive oxygen species (ROS) generated by photosensitizers. However, ROSs' ultrashort life span and limited diffusion distance restrict the PDT efficiency. Therefore, it is important to control the delivery strategy of photosensitizers for PDT treatment. Herein, the core-satellite nanoreactors were fabricated with oxygen generation and ROS diffusion properties. The hollow CuS encapsulating horseradish peroxidase (HRP) was combined with the cationic photosensitizers (PEI-Ce6). The unique photosensitizers delivery strategy makes the nanoreactors achieve ROS diffusion-enhanced PDT effect. First, HRP in "core" (HRP@CuS) can decompose hydrogen peroxide (H2O2) to O2, increasing O2 levels on the surface of the nanoreactor. Second, the Ce6 molecules covalent-linked with PEI are uniformly dispersed on the surface of CuS as a "satellite", avoiding Ce6 aggregation and causing more Ce6 molecules be activated to produce more 1O2. Due to the Ce6 was on the surface of the CuS nanocages, the generated ROS may ensure a larger diffusion range. Meanwhile, the inherently CuS nanocages exhibit photothermal and photoacoustic (PA) effect. The photothermal effect further enhances the ROS diffusion. Under the guidance of PA imaging, nanoreactors exhibit highly efficient hypoxic tumor ablation via photodynamic and photothermal effect. Overall, the core-satellite nanoreactors provide an effective strategy for tumor therapy, further promoting the research of photosensitizers delivery.
Subject(s)
Photochemotherapy , Photosensitizing Agents , Humans , Photosensitizing Agents/therapeutic use , Photochemotherapy/methods , Reactive Oxygen Species , Hydrogen Peroxide , Cell Line, Tumor , Phototherapy/methods , Oxygen , Hypoxia/drug therapy , NanotechnologyABSTRACT
Photodynamic therapy (PDT) is a promising cancer treatment method. Traditional small-molecule photosensitizers (PSs) suffer from low intersystem crossing (ISC) ability and aggregation-caused quenching (ACQ), which adversely affects the luminous efficiency and singlet oxygen (1O2) yield of PSs in the aggregated state. Ir(III) complexes are promising PSs with long excited-state lifetime, good photophysical and photochemical properties and large Stokes shifts. Aggregation-induced emission (AIE) characteristics could reduce the nonradiative recombination and improve the ISC ability of excited states through the restriction of the intramolecular motions in aggregated states. Accordingly, two AIE-active Ir(III) complexes Ir-1-N+ and Ir-2-N+ were successfully designed and obtained based on Schiff base ligands. Experimental results showed that Ir-1-N+ and Ir-2-N+ have good photophysical properties and the corresponding nanoparticles (NPs) have good water solubility and 1O2 generation ability. Notably, Ir-2-N+ NPs can be efficiently taken up by mouse breast cancer cells (4T1 cells) with good biocompatibility, low dark toxicity and excellent phototoxicity. This work demonstrates a versatile strategy for exploiting efficient transition metal PSs with a cationic ligand in PDT.
Subject(s)
Photochemotherapy , Photosensitizing Agents , Animals , Mice , Cations/chemistry , Ligands , Photochemotherapy/methods , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemistry , Schiff Bases , Cell Line, TumorABSTRACT
The integration of an aggregation induced emission (AIE)-active Ir(III) complex and upconversion nanoparticles (UCNPs) has achieved a NIR-irradiated photosensitizer (PS), UCNPs@Ir-2-N. This PS has satisfactory biocompatibility, excellent phototoxicity, good accumulation in cells and high 1O2 generation ability, thereby effectively killing 4T1 mouse cancer cells in vitro. This work has potential for future photodynamic therapy (PDT) applications.
Subject(s)
Nanoparticles , Photochemotherapy , Animals , Iridium/pharmacology , Mice , Photosensitizing Agents/pharmacologyABSTRACT
Nanozymes with multienzyme-mimicking activities have shown great potential in cancer therapy due to their ability to modulate the complex tumor microenvironment (TME). Herein, a second near-infrared (NIR-II) photothermal-nanocatalyst by decorating Bi2 Te3 nanosheets with ultrasmall Au/Pd bimetallic nanoparticles (Bi2 Te3 -Au/Pd) to reverse the immunosuppressive TME is developed. The peroxidase (POD)-like and catalase (CAT)-like activities, and glutathione (GSH) consumption capacity of Au/Pd modulates the TME by disrupting the intracellular redox homeostasis and relieving hypoxia in the TME. Notably, the amplified oxidative stress induces the accumulation of lipid hydroperoxides (LPO) for enhanced ferroptosis. Moreover, upon NIR-II photoirradiation at 1064 nm, the localized heat generated by Bi2 Te3 not only directly ablates the cancer cells but also enhances the Au/Pd-mediated catalysis-mediated cancer therapy. Furthermore, both in vitro and in vivo studies confirm that the Bi2 Te3 -Au/Pd nanocatalysts (BAP NCs) can effectively suppress tumor growth by inducing immunogenic cell death (ICD), and suppressing metastasis and recurrence by the synergistic treatment. Overall, this study provides a promising theranostic strategy for effective tumor inhibition.
Subject(s)
Nanoparticles , Neoplasms , Catalase , Cell Line, Tumor , Glutathione , Humans , Lipids , Neoplasms/drug therapy , Precision Medicine , Theranostic Nanomedicine , Tumor MicroenvironmentABSTRACT
Combating the concentration quenching effect by increasing the concentration of sensitized rare-earth ions in rational design upconversion nanostructure will make it easier to utilize injection energy flux and transfer it to emitters, resulting in improved upconversion luminescence (UCL). We proposed a host-sensitized nanostructure (active core@luminescent shell@inert shell) to improve multiphoton UCL of Tm3+ based on the LiLnF4 host. Yb3+ ions were isolated in the core as energy absorbents, and Tm3+ was doped in the interior LiYbF4 host shell. Compared with sandwich structured nanocrystals (Y@Y:Yb/Tm@Y), reverse structure (YbTm@Yb@Y), and fully doped structure (YbTm@YbTm@Y), the proposed structure achieved the highest efficiency of multiphoton UCL and favored a better FRET-based application performance as the Tm3+ located at an optimized spatial distribution. Furthermore, steady-state and dynamic analysis results demonstrate that by manipulating the spatial distribution of the active ions, excited energy can be tuned to enable multiphoton upconversion enhancement, overcoming the conventional limitations.
Subject(s)
Nanoparticles , Nanostructures , Luminescence , Nanoparticles/chemistryABSTRACT
Ferroptosis therapy (FT) is an attractive strategy to selectively damage cancer cells through lipid peroxide (LPO) over-accumulation. However, this therapy suffers from poor therapeutic efficacy due to the limited Fenton reaction efficiency and the evolved intrinsic resistance mechanism in the tumor microenvironment (TME). The exploitation of novel ferroptosis inducers is of significance for improving the efficacy of FT. Here, we develop a plate-like Bi2Se3-Fe3O4/Au (BFA) theranostic nanoplatform, which can increase the Fenton reaction rate to enhance FT in an active-passive way. In detail, benefiting from the internal synergistic effect of Fe3O4 NPs and Au NPs and external NIR-mediated hyperthermia, the BFA NPs can boost hydroxyl radical (ËOH) generation to enhance intracellular oxidative stress and further induce ferroptosis by inactivating glutathione peroxidase 4 (GPX4). Furthermore, the BFA NPs show high photothermal conversion efficiency in both the NIR-I and NIR-II windows (66.2% at 808 nm and 58.2% at 1064 nm, respectively); therefore, as a photothermal agent (PTA), they can also ablate cancer cells directly by NIR-triggered photothermal therapy (PTT). Meanwhile, BFA NPs could be used as an efficient diagnostic agent for photoacoustic (PA)/magnetic resonance (MR)/X-ray imaging to guide the synergistic therapy of photothermal-ferroptosis. Therefore, BFA NP-mediated enhanced photothermal-ferroptosis therapy represents a promising strategy for the application of nanomaterials in tumor therapy.
Subject(s)
Ferroptosis , Hyperthermia, Induced , Nanoparticles , Neoplasms , Cell Line, Tumor , Humans , Neoplasms/therapy , Photothermal Therapy , Theranostic Nanomedicine , Tumor MicroenvironmentABSTRACT
Photodynamic therapy (PDT) has been widely used in tumor therapy due to its high spatial-temporal control and noninvasiveness. However, its clinical application is limited by weak efficacy, shallow tissue penetration, and phototoxicity. Herein, a facile theranostic nanoplatform based on photoswitchable lanthanide-doped nanoparticles was designed. Typically, these nanoparticles had UV-blue and 1525 nm emission upon 980 nm excitation and 1525 nm emission upon 800 nm excitation. We further used these nanoparticles for achieving real-time near-infrared (NIR)-IIb imaging (800 nm) with a high signal-to-noise ratio and imaging-guided PDT (980 nm). Moreover, such a photoswitchable nanoplatform capping with pH-sensitive calcium phosphate for coloading doxorubicin (a chemotherapeutic immunogenic cell death [ICD] inducer) and paramagnetic Mn2+ ions enhances T1-magnetic resonance imaging in the tumor microenvironment. Our results suggest that this theranostic nanoplatform could not only kill tumor cells directly through dual-modal image-guided PDT/chemotherapy but also inhibit distant tumor and lung metastasis through ICD. Therefore, it has great potential for clinical application .
Subject(s)
Nanoparticles , Neoplasms , Photochemotherapy , Cell Line, Tumor , Doxorubicin/pharmacology , Doxorubicin/therapeutic use , Humans , Neoplasms/diagnostic imaging , Neoplasms/drug therapy , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Theranostic Nanomedicine , Tumor MicroenvironmentABSTRACT
Perovskite light-emitting devices (PeLEDs) have drawn a great deal of attention because of their exceptional optical and electrical properties. However, as for the blue PeLEDs based on low-dimensional (LD) CsPbBr3, the low conductivity of the widely used organic spacers as well as the difficulty of forming pure and uniform LD CsPbBr3 phase have severely inhibited the device performance such as stability and efficiency. In this work, we report an effective strategy to obtain high-quality LD CsPbBr3 by using a novel spacer of inorganic Cs4PbBr6 instead of the common long-chain ammonium halides. We found that a 3-amino-1-propanol (3AP)-modified PEDOT:PSS was helpful to stimulate the formation of the LD blue emissive CsPbBr3:Cs4PbBr6 composite. We also revealed that an additive of poly(vinylpyrrolidone) (PVP) in the precursor can limit further growth of LD perovskite phase into 3D perovskite phase upon annealing, thus resulting in a uniformly distributed LD perovskite with high color stability. Consequently, efficient blue PeLEDs @ 485 nm with a brightness of 2192 cd/m2, current efficiency of 2.68 cd/A, and external quantum efficiency of 2.3% was successfully achieved. More importantly, the device showed much improved working stability compared to those with the spacer of organic ammonium halides. Our results provide some helpful insights into developing efficient and stable blue PeLEDs.
ABSTRACT
Traditional sensitizer (Yb3+ or Nd3+) and activator (Er3+) co-doped lanthanide-based nanoprobes possessing emission of Er3+ at 1525 nm have attracted much attention in NIR-IIb bio-imaging. However, the 1525 nm fluorescence efficiency was not high enough in such co-doped systems due to the serious back energy transfer from the activator to the sensitizer, resulting in a lot of excitation energy loss. Herein, we have designed an efficient NIR-IIb nanoprobe Er3+ self-sensitized NaErF4:0.5%Tm3+@NaLuF4, where substantially all the excitation energy could contribute to Er3+ ions and most energy transfer processes were confined among Er3+ ions, avoiding the energy dissipation by heterogeneous sensitizer ions. The influence of the types of epitaxial heterogeneous shells, the doping effect and optimal doping concentration of Tm3+ ions, as well as the critical shell thickness for obtaining the surface quenching-assisted downshifting emission are systematically investigated to acquire the most efficient 1525 nm luminescence under 800 nm excitation. The quantum yield in the 1500-1700 nm region reached 13.92%, enabling high-resolution through-skull cerebrovascular microscopy imaging and large-depth in vivo physiological dynamic imaging with an extremely low excitation powder density of 35 mW cm-2. The designed nanoprobe can be potentially used for brain science research and clinical diagnosis.
Subject(s)
Blood Vessels/diagnostic imaging , Brain/diagnostic imaging , Erbium/chemistry , Metal Nanoparticles/chemistry , Optical Imaging , Animals , Infrared Rays , Mice , Particle Size , Surface PropertiesABSTRACT
Cancer incidence and mortality are fast growing worldwide. Recently, multiplexing imaging methods have been reported to be vital for cancer diagnosis and therapy. Fluorescence imaging, which has intrinsic capabilities for multiplexing imaging, is suitable and ripe for cancer imaging. In biomedical research, using a single probe for multiplexing imaging can avoid larger invasive effects and ensure the same spatiotemporal distributions and metabolisms of the probes, which has advantages over using multiple probes. Therefore, developing unimolecular fluorescent probes for multiplexing imaging of living cancer cells is meaningful. We herein report a unimolecular fluorescent probe (ZED) that simultaneously detects cysteine/homocysteine, hypochlorous acid, mitochondrial membrane potential (Δψm), and opening of the mitochondrial permeability transition (MPT) pore in cells. These four analytes are key indicators predominantly associated with multiple aspects of carcinogenesis and cancer therapy in living cells. Besides, ZED also differentiates MCF-7 cells from HBL-100 cells. The sensing process is fast, selective, and sensitive in living cancer cells. As far as we know, ZED is the first probe that simultaneously detects four analytes in cells and the first probe that simultaneously detects Δψm and opening of the MPT pore in mitochondria.
Subject(s)
Coumarins/chemistry , Fluorescent Dyes/chemistry , Imidazoles/chemistry , Mitochondria/metabolism , Rhodamines/chemistry , Cell Line, Tumor , Cysteine/analysis , Homocysteine/analysis , Humans , Hypochlorous Acid/analysis , Limit of Detection , Membrane Potential, Mitochondrial/physiology , Microscopy, Confocal , Microscopy, Fluorescence , Mitochondrial Permeability Transition Pore/metabolismABSTRACT
Photodynamic therapy (PDT) is one of the non-invasive and selective treatment methodologies for cancer. However, many highly efficient photosensitizers (PSs) are usually low physiological solubility, limited bioavailability and tending aggregation, impeding the effectiveness of PDT, as well as cancer resistance of PDT further reduce its therapeutic effect. Though some smart delivery systems have been developed, the problem of photosensitizer leakage/release has not been completely solved. Herein, we developed a smart therapeutic nanoplatform based on polyphotosensitizer nanogel as novel nanophotosensitizers and drug carriers. Moreover, by loading of histone deacetylase inhibitors (SAHA), it allows for enhanced synergistic therapy strategy of prostate cancer via inhibiting HIF-1α and VEGF pathways of cancer cells involved in PDT resistance. Our study presents the well-designed nanoplatform of nanogel-Ce6, which could serve as a photodynamic agent without Ce6 molecules release in the responsive environment, offering the potential to encapsulate diverse functional components for smart drug release and imaging-guided combination therapy in vitro and in vivo.
Subject(s)
Antineoplastic Agents/pharmacology , Histone Deacetylase Inhibitors/pharmacology , Histone Deacetylases/metabolism , Nanogels/chemistry , Photochemotherapy , Photosensitizing Agents/pharmacology , Animals , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Drug Screening Assays, Antitumor , Histone Deacetylase Inhibitors/chemistry , Humans , Male , Mice , Mice, Inbred C57BL , Molecular Structure , Neoplasms, Experimental/drug therapy , Neoplasms, Experimental/metabolism , Neoplasms, Experimental/pathology , PC-3 Cells , Particle Size , Photosensitizing Agents/chemistry , Surface PropertiesABSTRACT
Side effect is one of the main factors affecting the success of cancer therapies in clinic. Patients treated with photodynamic therapy (PDT) suffer mainly from the phototoxicity due to the relatively long time blood circulation of the tumor enrichment and they have also to be protected from background light for days after the treatment. Here we introduce a new design of nanophotosensitizers in which the luminescence upconversion nanoparticles loaded with photosensitizers are self-assembled into a nanoball with the aid of a specific pH-sensitive polymer layer containing overloaded photosensitizers and quenching molecules. This design makes the therapy function "off/on" possible, i.e. only imaging during the circulation of the nanoballs ascribing to the near-infrared (NIR) photon upconversion of the nanoballs and the pH-sensitive shell. Activation of PDT solely occurs once the nanoballs are taken up by the cancer cells due to the acidic microenvironment. This design prevents effectively the photodamage of the photosensitizers during enrichment and targeting process of tumor, as validated in vitro and in vivo, which enables imaging-guided PDT treatment of deep-seated tumor in a much more relax and comfortable way for patients. This patient-friendly nanomaterial construction strategy can also be extended to other therapies.
Subject(s)
Nanoparticles , Neoplasms , Photochemotherapy , Humans , Hydrogen-Ion Concentration , Neoplasms/diagnostic imaging , Neoplasms/drug therapy , Optical Imaging , Photosensitizing Agents/therapeutic use , Tumor MicroenvironmentABSTRACT
A perfect "off" to "on" switch of the therapeutic function is very important to minimize the phototoxicity of nanoplatforms assisted imaging-guided photodynamic therapy (PDT) of cancer. Current approaches rely on preloaded photosensitizers, where the off/on state of PDT is regulated by the sensitizing light of photosensitizers. However, the photoactivities inevitably occur when imaging/diagnosis or exposure to sunlight, etc. These preloading approaches will cause the damage to normal cells and the photosensitivity to the skin. Taking upconversion photodynamic therapy as an example we report here a biorthogonal chemistry solution to circumvent this problem. The luminescence upconversion nanoparticles (UCNPs) are anchored with one handle of click reaction and targeting entity, these nanoplatforms enable the imaging/labelling/tracking, especially for imaging-guided surgery. Once they are targeted, the photosensitizers armed with the other match handle will be injected in situ and click reaction will occur between the two handles to link the photosensitizers closely with the targeted nanoplatforms in a very short time, enabling the PDT function of the nanoplatforms. Proof of principle has been demonstrated in vitro and in vivo. This approach can be readily extended to chemotherapy, radiotherapy, etc. to overcome the side effect of these therapies of cancers.