Photodynamic Therapy Of Tumors Research Articles

Hollow Mesoporous MnO2 Nanospheres as Light Source-Free Carriers for Synergistic Starvation and Chemiexcited Photodynamic Tumor Therapy

Hollow Mesoporous MnO₂ Nanospheres as Light Source-Free Carriers for Synergistic Starvation and Chemiexcited Photodynamic Tumor Therapy

Indocyanine green-equipped upconversion nanoparticles/CeO2 trigger mutually reinforced dual photodynamic therapy

Although photodynamic-based tumor therapy has attracted considerable attention, the antitumor effect is limited due to the low reactive oxygen species (ROS) generation of photosensitizers. Therefore, it is an urgent need for improving ROS production and promoting therapeutic outcome of tumor. We developed a nanoplatform of indocyanine green (ICG)-equipped upconversion nanoparticles (UCNPs)/CeO2 modified with NH2-PEG1000-cRGDfK (UICCIP). This nanoplatform has two pathways of ROS production for mutually enhanced dual photodynamic therapy (PDT) of tumors. The ultraviolet (UV) emission of UCNPs could trigger CeO2 to produce ROS for PDT under 808 nm laser irradiation, and ICG can also produce singlet oxygen (1O2) at the meantime. Importantly, ICG can enhance the luminescence of UCNPs through energy transfer, thus promoting the PDT effect of CeO2. For another, CeO2 could catalyze endogenous H2O2 to provide O2 then overcome the hypoxic environment of tumor to enhance the PDT effect. By highlighting the full use of the various components of the nanoplatform and establishing interrelationships, ROS production can be increased significantly, resulting in efficient PDT of tumor. It is believed that UICCIP will become a potential ROS producer, which will broaden the thought of exploring new antitumor nanoplatforms.

A targeted phototheranostic agent with strong AIE effect and boosted type I ROS generation

Hypoxia and nonspecific killing always hinder the photodynamic therapy of malignant tumors and infectious diseases that both severely threatening human health. Herein, we report a type I photosensitizer (MTOTPy) with aggregation-induced near-infrared (NIR) emission feature and specific identification ability by rational molecular design. Enhanced electron-donating effect and electron-rich anion-π+ structure endow MTOTPy with strong NIR fluorescence and intensive type I reactive oxygen species generation in aggregation. It is demonstrated that MTOTPy can achieve fast identification of tumor cells by targeting mitochondria and specific recognition of Staphylococcus aureus (S. aureus) among other kinds of microbes. Moreover, MTOTPy can kill more than 90% tumor cells and S. aureus upon visible light irradiation at low concentration of 5.0 μM and 0.5 μM, respectively. The work provides a feasible idea for designing photosensitizers to overcome the hypoxic limitation of photodynamic therapy and advance the development of image-guided therapy with high efficiency.

Porous SiO2-Based Reactor with Self-Supply of O2 and H2O2 for Synergistic Photo-Thermal/Photodynamic Therapy.

Although the combined photo-thermal (PTT) and photodynamic therapy (PDT) of tumors have demonstrated promise as effective cancer therapy, the hypoxic and insufficient H2O2 supply of tumors seriously limits the efficacy of PDT, and the acidic environment reduces the catalytic activity of nanomaterial in the tumor microenvironment. To develop a platform for efficiently addressing these challenges, we constructed a nanomaterial of Aptamer@dox/GOD-MnO2-SiO2@HGNs-Fc@Ce6 (AMS) for combination tumor therapy. The treatment effects of AMS were evaluated both in vitro and in vivo. In this work, Ce6 and hemin were loaded on graphene (GO) through π-π conjugation, and Fc was connected to GO via amide bond. The HGNs-Fc@Ce6 was loaded into SiO2, and coated with dopamine. Then, MnO2 was modified on the SiO2. Finally, AS1411-aptamer@dox and GOD were fixed to gain AMS. We characterized the morphology, size, and zeta potential of AMS. The oxygen and reactive oxygen species (ROS) production properties of AMS were analyzed. The cytotoxicity of AMS was detected by MTT and calcein-AM/PI assays. The apoptosis of AMS to a tumor cell was estimated with a JC-1 probe, and the ROS level was detected with a 2',7'-Dichlorodihydrofluorescein diacetate (DCFH-DA) probe. The anticancer efficacy in vivo was analyzed by the changes in the tumor size in different treatment groups. AMS was targeted to the tumor cell and released doxorubicin. It decomposed glucose to produce H2O2 in the GOD-mediated reaction. The generated sufficient H2O2 was catalyzed by MnO2 and HGNs-Fc@Ce6 to produce O2 and free radicals (•OH), respectively. The increased oxygen content improved the hypoxic environment of the tumor and effectively reduced the resistance to PDT. The generated •OH enhanced the ROS treatment. Moreover, AMS depicted a good photo-thermal effect. The results revealed that AMS had an excellent enhanced therapy effect by combining synergistic PTT and PDT.

Calcium carbonate nanoparticles tumor delivery for combined chemo-photodynamic therapy: Comparison of local and systemic administration.

The use of nanoparticles (NPs) as delivery vehicles for multiple drugs is an intensively developing area. However, the success of NPs' accumulation in the tumor area for efficient tumor treatment has been recently questioned. Distribution of NPs in a laboratory animal is mainly related to the administration route of NPs and their physicochemical parameters, which significantly affect the delivery efficiency. In this work, we aim to compare the therapeutic efficiency and side effects of the delivery of multiple therapeutic agents with NPs by both intravenous and intratumoral injections. For this, we systematically developed universal nanosized carriers based on calcium carbonate (CaCO3) NPs (< 100nm) that were co-loaded with a photosensitizer (Chlorin e6, Ce6) and chemotherapeutic agent (doxorubicin, Dox) for combined chemo- and photodynamic therapy (PDT) of B16-F10 melanoma tumors. By performing intratumoral or intravenous injections of NPs, we observed different biodistribution profiles and tumor accumulation efficiencies. In particular, after intratumoral administration of NPs, they mostly remained in the tumors (> 97%); while for intravenous injection, the tumor accumulation of NPs was determined to be 8.67-12.4 ID/g%. Although the delivery efficiency of NPs (presented in ID/g%) in the tumor differs, we have developed an effective strategy for tumor inhibition based on combined chemo- and PDT by both intratumoral and intravenous injections of NPs. Notably, after the combined chemo- and PDT treatment with Ce6/Dox@CaCO3 NPs, all B16-F10 melanoma tumors in mice shrank substantially, by approximately 94% for intratumoral injection and 71% for intravenous injection, which are higher values compared to mono-therapy. In addition, the CaCO3 NPs showed negligible in vivo toxicity towards major organs such as the heart, lungs, liver, kidneys, and spleen. Thus, this work demonstrates a successful approach for the enhancement of NPs' efficiency in combined anti-tumor therapy.

Novel anthraquinone photosensitizers: Synthesis, photoactivity, and 3D-QSAR studies

In this study, three-dimensional quantitative conformational relationship (3D-QSAR) analysis was conducted on 38 known anthraquinone derivatives. Additionally, five pH-responsive anthraquinone photosensitizers (A1 to A5) were designed and synthesized through addition, elimination, and substitution mechanisms using the anthraquinone derivative chrysophanol as the raw material. The structures of the products were characterized using 1HNMR, 13CNMR , LCMS, and the UV–Vis absorption spectra and fluorescent spectra at different pH values were obtained. To investigate the photodynamic antibacterial activity of the compounds, their inhibitory activities against Pseudomonas aeruginosa and Staphylococcus aureus were tested in vitro under different light and pH conditions. The results showed that the compounds exhibited good photodynamic antibacterial activity and selectivity in light and weak acid environments. MTT experiments were conducted to evaluate the cytotoxicity of the compounds on the human cancer cell line HeLa. It was found that the phototoxicity and dark toxicity effects of compound A3 at concentrations of 0.625 μM and lower were similar to those of the reference photosensitizer Chlorin e6 (Ce6). However, the amount of singlet oxygen produced by A3 was approximately 7.6 times that produced by Ce6, indicating its potential for application in the photodynamic therapy of tumours and providing a reference for research on anthraquinone photosensitizers.

Integration of Activation by Hypoxia and Inhibition Resistance of Tumor Cells to Apoptosis for Precise and Augmented Photodynamic Therapy.

Photodynamic therapy (PDT) uses photosensitizers to convert oxygen (O2 ) to reactive oxygen species (ROS) under irradiation to induce DNA damage and kill cancer cells. However, the effect of PDT is usually alleviated by apoptosis resistance mechanism of tumor living cells. MTH1 enzyme is known to be such an apoptosis-resistance enzyme which is over expressed as a scavenger to repair the damaged DNA. In this work, a hypoxia-activated nanosystem FTPA, which can be degraded to release the encapsulated PDT photosensitizer 4-DCF-MPYM and an inhibitor TH588 is proposed. The inhibitor TH588 can inhibit the DNA repair process by reducing the activity of MTH1 enzyme, and achieve the purpose of amplifying the therapeutic effect of PDT. This work demonstrates that a precise and augmented tumor PDT is achieved by integration of hypoxia-activation and inhibition resistance of tumor cells to apoptosis.

Bimetallic Ions Functionalized Metal-Organic-Framework Nanozyme for Tumor Microenvironment Regulating and Enhanced Photodynamic Therapy for Hypoxic Tumor.

Photodynamic therapy (PDT), as a light irradiation inducing reactive oxygen species (ROS) generation for cancer treatment, offers facile and promising solutions with respect to spatiotemporal control of ROS generation, and minimizes the systemic toxicity and side effects for highly precise tumor therapy. However, the PDT efficiency is often severely compromised by the complex tumor microenvironment (TME), such as the hypoxic condition and overexpressed antioxidants. Here, for the first time, a bimetallic ion-modified metal-organic framework nanozyme (Zr4+ -MOF-Ru3+ /Pt4+ -Ce6@HA, ZMRPC@HA) is designed. ZMRPC@HA with catalase (CAT) and glutathione oxidase (GSHOx) mimetic activities, can efficiently regulate TME by generation of O2 and deplete the GSH synergistically for enhancing the long-term PDT efficacy toward the hypoxic tumor. The in vitro cell inhibition and in vivo on tumor xenograft evaluations demonstrate the PDT strategy by using ZMRPC@HA can successfully inhibit the differentiation and proliferation of tumor cells under a 660nm laser irradiation in deep tissues. These findings open a new avenue for the design of multimetallic ions functionalized MOF-based nanozymes with multienzyme mimetic activities toward the antitumor and various other biological applications.

SIRIUS, Ultra-Scintillating Upconversion Breast Implant for Remote Orthotopic Photodynamic Therapy.

Present day strategies for delivery of wireless photodynamic therapy (PDT) to deep-seated targets are limited by the inadequacy of irradiance and insufficient therapeutic depth. Here we report the design and preclinical validation of a flexible wireless upconversion nanoparticle (UCNP) implant (SIRIUS) that is capable of large field, high intensity illumination for PDT of deep-seated tumors. The implant achieves this by incorporating submicrometer core-shell-shell NaYF4 UCNPs into its design, which significantly enhances upconversion efficiency and mitigates light loss from surface quenching. We demonstrate the efficacy of SIRIUS UCNP implant mediated PDT in preclinical breast cancer disease models. In our in vitro experiments, SIRIUS directed 5-Aminolevulinic Acid (5-ALA) based wireless PDT leads to significant reactive oxygen species (ROS) generation and tumor apoptosis in hormonal receptor+/HER2+ (MCF7) and triple-negative (MDA-MB-231) breast cancer cell lines. In our in vivo rodent model, SIRIUS-driven PDT is shown to be significant in regressing tumors when applied to orthotopically inoculated breast tumors. Following successful preclinical validation, we also describe a clinical prototype of UCNP breast implant with potential dual cosmetic and onco-therapeutic functions. SIRIUS is an upconversion breast implant for wireless PDT that fulfils all the design prerequisites necessary for seamless clinical translation.

Drug induced mitochondria dysfunction to enhance photodynamic therapy of hypoxic tumors.

As most solid tumors are characterized by a hypoxic microenvironment, enormous efforts have been made to develop strategies to fight hypoxia. This study shows that ivermectin (IVM), an antiparasitic drug, is able to alleviate tumor hypoxia by inhibiting mitochondrial respiration. We explore this to strengthen oxygen-dependent photodynamic therapy (PDT) using chlorin e6 (Ce6) as a photosensitizer. To synergize their pharmacological behaviors, Ce6 and IVM are encapsulated into stable Pluronic F127 micelles. The micelles are uniform in size and seem well-suited for the co-delivery of Ce6 and IVM. The micelles could passively target the drugs into tumors and enhance their cellular internalization. Most importantly, through mitochondrial dysfunction, the micelles reduce the oxygen consumption (making the tumor less hypoxic). Consequently, the production of reactive oxygen species would be increase which, in turn, improves the efficacy of PDT against hypoxic tumors.

A viscosity-sensitive and mitochondria-targeted AIEgen effectuated fatty liver imaging and cancer photodynamic therapy

The mitochondrial targeting and viscosity-sensitive near-infrared fluorescence probe TQS-OH was an aggregation induced emission luminogen constructed by regulating the receptor structure and hydroxylating its terminal. TQS-OH presented more than 27.35-fold fluorescence enhancement at the maximum emission peak when the viscosity level increased from 0.49 to 1048 cP. It also appeared excellent reactive oxygen species production ability under white light irradiation and appeared strong photodynamic therapied effect on HepG2 cells. In addition, cellular co-location analysis implied that TQS-OH had accurate mitochondrial targeting ability, with co-location coefficient up to 0.95 in human hepatocellular carcinoma HepG2 cells and it also successfully achieved fatty liver imaging. Meanwhile, we found that TQS-OH induced cancer cell apoptosis by activating mitochondrial apoptosis pathway. Furthermore, TQS-OH ultimately has implemented the tumor photodynamic therapy with high efficiency in vivo, with a tumor inhibition rate as high as 50.77%. The above results made it a promising aggregation induced emission material for the diagnosis of fatty liver and tumor phototherapy.

Light-Elicited and Oxygen-Saved Iridium Nanocapsule for Oxidative Damage Intensified Oncotherapy.

Regulating redox homeostasis in tumor cells and exploiting oxidative stress to damage tumors is an efficacious strategy for cancer therapy. However, the strengths of organic nanomaterials within this strategy are often ignored. In this work, a light-triggered reactive oxygen species (ROS) damaging nanoamplifier (IrP-T) was developed for enhanced photodynamic therapy (PDT). The IrP-T was fabricated with an amphiphilic iridium complex and a MTH1 inhibitor (TH287). Under green light stimulation, IrP-T catalyzed the oxygen in cells to generate ROS for realizing oxidative damage; meanwhile, TH287 increased the accumulation of 8-oxo-dGTP, further strengthening oxidative stress and inducing cell death. IrP-T could maximize the use of a small amount of oxygen, thus further boosting the efficacy of PDT in hypoxic tumors. The construction of nanocapsules provided a valuable therapeutic strategy for oxidative damage and synergizing PDT.

Dual-Photosensitizer Nanoplatform Based on Near-Infrared Excitation Orthogonal Emission Nanomaterials for Enhanced Photodynamic Therapy of Tumors.

Photodynamic therapy (PDT) is considered as a promising therapeutic approach for clinical cancer treatment. However, the hypoxia of the tumor microenvironment leads to the low effect of single PDT. Here, a dual-photosensitizer nanoplatform based on near-infrared excitation orthogonal emission nanomaterials is constructed by introducing two kinds of photosensitizers into the nanosystem. Orthogonal emission upconversion nanoparticles (OE-UCNPs) were used as light conversion reagents to generate red emission under 980 nm irradiation and green emission under 808 nm irradiation. On the one hand, merocyanine 540 (MC540) is introduced as a photosensitizer (PS), which can absorb green light to generate reactive oxygen species (ROS) and trigger PDT for tumor treatment. On the other hand, another photosensitizer, chlorophyll a (Chla), which can be excited by red light, has also been introduced into the system to build a dual PDT nanotherapeutic platform. The introduction of photosensitizer Chla can synergistically increase ROS concentration to accelerate cancer cell apoptosis. Our research shows that this dual PDT nanotherapeutic platform combined with Chla has better therapeutic effects and effectively destroys cancer.

5-ALA photodynamic ablation of fibroblastic soft-tissue tumors

Background: Fibroblastic soft-tissue tumors share enzymatic anomalies that result in excessive intracellular conversion of 5-aminolevulinic acid (5-ALA) to protoporphyrin IX, a photosensitizer which induces cellular apoptosis upon exposure to visible red light at a wavelength of 635 nm. We hypothesized that red light illumination of the surgical bed remaining after resection of fibroblastic tumors will result in destruction of microscopic tumor residua and may decrease the likelihood of local tumor recurrence. Methods: Twenty-four patients with desmoid tumors, solitary fibrous tumors (SFT), and dermatofibrosarcoma protuberans (DFSP) received oral 5-ALA prior to resection of their tumors. Following tumor resection, the exposed surgical bed was illuminated with red light at a wave length of 635 nm at a dose of 150 J/cm2 for 33 min. Results: Treatment with 5-ALA was associated with minor side effects that included nausea and transient elevation of transaminases. Local tumor recurrence was detected in 1 of the 10 patients with desmoid tumors who had not undergone any previous surgery, none in the 6 patients who had SFT and 1 of the 5 patients who had DFSP. Conclusions: 5-ALA photodynamic therapy of fibroblastic soft-tissue tumors may result in decreased likelihood of local tumor recurrence. It is associated with minimal side effects and should be considered as adjuvant to tumor resection in these cases.

Perovskite-derived pro-photosensitizer enables sustainable photodynamic therapy in hypoxia tumors

Perovskite of superior photocatalysis renders attractive potential in photodynamic therapy (PDT), but compromise in biomedical applications due to intrinsic susceptible hydrolysis and safety concerns. Here, a trilaminar-structured, hyaluronidase-responsive pro-photosensitizer (HMT) is fabricated by perovskite (MASnI3)-titanium dioxide (TiO2)-hyaluronic acid (HA) ploygel passivator for advanced cytoplasm-specific sustainable PDT. Structurally, an efficient electron-hole transfer medium of TiO2 was deposited onto MASnI3 for hydrolysis-resistance, which could give robust hydroxyl radical production in hypoxia. The HMT is passivated by HA-gel clicking for bio-stabilization, tumor-specific penetration and cellular internalization. The HA-corona detachment by hyaluronidase in tumor triggers revitalization of photoinduced-hydrogen-abstraction, promising instant ROS generation. After topical administration, HMT induces complete tumor elimination via mitochondria damage upon multi-cycle NIR irradiation. Moreover, no side-effect is noted in toxicity study, potentially profiting from topical application, tumor targeting and minimized dosage by multi-cycle irradiation. Collectively, we herein propose a pioneering perovskite photosensitizer for non-oxygen dependent PDT.

Solvothermal synthesis of rhombic shape GdF&lt;sub&gt;3&lt;/sub&gt;:Tb&lt;sup&gt;3+&lt;/sup&gt; nanoparticles for biomedical applications

Purpose of the study. In this work, we have investigated the mechanism of structure formation of GdF3:Tb3+(15 %) nanocrystals synthesized by solvothermal synthesis in the temperature range from RT to 200 °C with a step of 50 °C.Materials and methods. Nanocrystals of GdF3:Tb3+(15 %) were synthesized by the solvothermal method using a high-pressure reactor (autoclave) designed for temperatures up to 250 °C. The structure, size and morphology were determined by transmission electron microscopy (TEM), the type of crystal lattice and the size of crystallites of nanoparticles were studied by X-ray diffraction (XRD), hydrodynamic size of nanoparticles, particle size distribution, ζ-potential, agglomeration of nanoparticles in colloidal solutions were determined by dynamic light scattering (DLS), the chemical composition of the nanocrystals surface was studied by Fourier-t ransform infra-red spectroscopy (FT-IR), the nanoparticles ability to absorb UV radiation was analyzed by UV-visible spectroscopy (UV-vis) and X-ray excited optical luminescence (XEOL).Results. With an increase in the temperature of the synthesis reaction, a structural change in the crystallites phase occurs from hexagonal to orthorhombic. At low temperatures, agglomerated particles consisting of hexagonal nanocrystals are formed, while at a temperature higher than the boiling point of the solvent, monodisperse rhombic- shaped nanoparticles with orthorhombic phase are formed. At mild temperatures, agglomerated particles with different morphology and with mixed hexagonal and orthorhombic phases are formed. Based on the analysis of X-ray spectrum, it was found that the size of GdF3:Tb3+(15 %) nanocrystals varies from 10 to 50 nm for different synthesis temperature conditions (T = RT, 50 °C, 100 °C, 150 °C, 200 °C). The hydrodynamic size of nanoparticles decreases with increasing synthesis temperature. All GdF3:Tb3+(15 %) nanocrystals obtained at different temperatures are transparent to visible light and absorb UV radiation. Absorption in the UV region increases with an increase in the size of particle crystallites. Upon X-ray irradiation of the colloidal GdF3:Tb3+(15 %) solution, X-ray excited optical luminescence spectra showed emission peaks at 490 nm, 543 nm, 585 nm and 620 nm.Conclusion. The mechanism of structure formation of rhombic‑ shaped GdF3:Tb3+(15 %) nanocrystals has been investigated. These monodisperse rhombic- shaped nanoparticles can be used for X-ray induced photodynamic therapy (X-PDT) of superficial, solid and deep-seated tumors.

Fe(III)-coordination-driven fabrication of self-supplying oxygen and charge-convertible nanoplatform for enhanced photodynamic therapy of tumor

The hypoxic microenvironment of tumors severely limits the effect of oxygen-dependent photodynamic therapy. Coordination-induced self-assemblies fabricate from metal ions and polymer ligands present potential advantages in catalytic reaction-mediated O2 production, high drug loading efficiency and system stability, as well as enhanced tumor targeting. In this work, self-supplying O2 and pH-induced charge-convertible nanoplatforms (termed as Sp-NPs) were fabricated through coordination-induced self-assembly of meso-tetrakis(4-carboxyphenyl)porphyrin (TCPP) modified and carboxylated pH sensitive polymeric ligand, poly (isobutylene-alt-maleic anhydride-conjugated-methoxy-poly(ethyleneglycol)-conjugated-imidazole-conjugated-ethylenediamine-grafted-TCPP) [PIMA-mPEG-API-EDA-TCPP], and ferric ions (Fe3+) for enhanced photodynamic therapy of cancer. The Sp-NPs displays uniform elliptic nanoparticles with size of around 90 nm and excellent stability in a variety of biomimetic biological media. Moreover, Sp-NPs bearing charge-convertible feature can flip the surface charge from negative to positive in the weakly acidic tumor extracellular condition, resulting in enhanced the cellular internalization. After entering more acidity tumor cells by endocytosis, Sp-NPs can be detonated to activate photosensitizers and release Fe3+ that can catalyze endogenous hydrogen peroxide (H2O2) to produce O2, leading to a prominent enhancement of fluorescence imaging and reactive oxygen species (ROS) generation in the tumor. Importantly, this nanoplatform exhibits a more potent cancer cell killing efficiency with good biosafety compared to that were treated with free TCPP. Therefore, incorporation self-oxygenation-boosted ROS strategy and pH-induced charge-convertible mechanism into this platform offered a great promise for cancer therapy.

Mitochondria-targeted Janus mesoporous nanoplatform for tumor photodynamic therapy

Photodynamic therapy (PDT) is an effective treatment method for tumors. But the specifically accumulated of photosensitizer was very difficult in the tumor site, which greatly limited the efficacy of PDT. Here, mitochondria-targeted Janus mesoporous nanoplatform (JPMO-Pt-CTPP-ZnPc) for PDT was prepared, the nanoplatform has uniform size (275 nm) and good dispersion and biocompatibility. The confocal laser scanning microscopy (CLSM) revealed the signal of ZnPc of JPMO-Pt-CTPP-ZnPc were higher than JPMO-Pt-ZnPc in tumor cells, and flow cytometry results showed the cell uptake efficiency of JPMO-Pt-CTPP-ZnPc was 2.5-fold higher than that of JPMO-Pt-ZnPc. This revealed the modification of CTPP significantly improves the targeting ability of the nanoplatform. In vitro anti-tumor experiment showed the JPMO-Pt-CTPP-ZnPc significantly inhibited the growth of tumor cells upon the irradiation of low-power laser, and the survival rate of cells incubated with 60 µg/mL JPMO-Pt-CTPP-ZnPc was only 3%. Simultaneously, compared with JPMO-Pt-ZnPc (not modified with mitochondria targeting molecules CTPP), the PDT efficacy of JPMO-Pt-CTPP-ZnPc was significantly better, as it has targeted mitochondria in cells.

Cytotoxicity Evaluation of Photosensitizer-Conjugated Hexagonal Upconverting Nanoparticles.

In this report, we synthesized hexagonal NaYF4:Yb,Er upconverting nanoparticles (UCNPs) of 171 nm in size with a narrow particle size distribution. To address their colloidal stabi-lity in aqueous media and to incorporate a photosensitizer that can produce reactive singlet oxygen (1O2) to kill tumor cells, UCNPs were conjugated with 6-bromohexanoic acid-functionalized Rose Bengal (RB) and coated with PEG-alendronate (PEG-Ale). The particles were thoroughly characterized by transmission electron microscopy, dynamic light scattering, ATR FTIR, X-ray photoelectron spectroscopy, thermogravimetric analysis, and spectrofluorometry, and 1O2 formation was detected using a 9,10-diphenylanthracene spectrophotometric probe. Cytotoxicity determination on rat mesenchymal stem cells by using the MTT assay showed that neutralization of the large positive surface charge of neat UCNPs with PEG-Ale and the bound RB sensitizer significantly reduced the concentration-dependent cytotoxicity. The presented strategy shows great potential for the use of these particles as a novel agent for the photodynamic therapy of tumors.

Photomodulation Approaches to Overcome Antimicrobial Resistance.

Photopharmacology is an approach that aims to be an alternative to classical chemotherapy. Herein, the different classes of photoswitches and photocleavage compounds and their biological applications are described. Proteolysis targeting chimeras (PROTACs) containing azobenzene moieties (PHOTACs) and photocleavable protecting groups (photocaged PROTACs) are also mentioned. Furthermore, porphyrins are referenced as successful photoactive compounds in a clinical context, such as in the photodynamic therapy of tumours as well as preventing antimicrobial resistance, namely in bacteria. Porphyrins combining photoswitches and photocleavage systems are highlighted, taking advantage of both photopharmacology and photodynamic action. Finally, porphyrins with antibacterial activity are described, taking advantage of the synergistic effect of photodynamic treatment and antibiotic therapy to overcome bacterial resistance.