RESUMO
Nanocatalysts with photodynamic therapy (PDT) and chemodynamic therapy (CDT) are excellent for tumor therapy. However, it is still challenging to achieve complete tumor eradication due to the drawbacks of limited penetration depth of intratumoural tissues, hypoxia and complexity of the tumor microenvironment (TME). Herein, we fabricated an integrated multifunctional nanoreactor (LuAG:Tb/Ce-RB@ZIF-8-Au2Pt-HA, LRZAPH) combining scintillating nanoparticles (SCNPs, LuAG:Tb/Ce), a metal-organic framework (ZIF-8), and bimetallic Au2Pt for X-ray-triggered PDT and dual noble-metal nanozyme catalyzed CDT. Such a nanoreactor not only significantly enhanced the PDT effect under X-ray irradiation through full resonance energy transfer from LuAG:Tb/Ce scintillator to Ross Bengal (RB), but also facilitated the reactive oxygen species (ROS) and oxygen (O2) production through the excellent peroxidase-like (POD-like) and catalase-like (CAT-like) catalytic properties of Au2Pt nanozymes. O2 also alleviates hypoxia in intratumoural tissues during coordinated PDT. In addition, the dissociation behavior of ZIF-8 with pH-responsive and targeted of hyaluronic acid (HA) in acidic TME significantly enhanced the therapeutic efficacy of LRZAPH nanocatalysts. Significantly, the high tumor growth inhibition rate of 93 % was revealed due to radiotherapy (RT)/PDT/CDT synergetic therapy in vivo, which minimized the toxic and side effects of conventional clinical radiotherapy/chemotherapy on human. The synergistic effect of LRZAPH nanocatalysts on PDT and catalytically induced CDT is expected to provide new pathways for effective treatment of deep tumors.
Assuntos
Fotoquimioterapia , Animais , Camundongos , Humanos , Catálise , Raios X , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Camundongos Endogâmicos BALB C , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Ouro/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Nanopartículas/química , FemininoRESUMO
Nanoparticles have become versatile assets in the medical field, providing notable benefits across diverse medical arenas including controlled drug delivery, imaging, and immunological assays. Among these, non-lamellar lipid nanoparticles, notably cubosomes and hexosomes, showcase remarkable biocompatibility and stability, rendering them as optimal choices for theranostic applications. Particularly, incorporating edge activators like sodium taurocholate enhances the potential of these nanoparticles for dermal and transdermal drug delivery, overcoming the stratum corneum, a first line of defense in our skin. This study reports on the formulation of monoolein-based cubosomes and hexosomes incorporating taurocholate and stabilized by Span 80 and co-encapsulating Chlorin e6 and coenzyme QH for photodynamic therapy in skin metastatic melanoma. The formulations were optimized using small-angle X-ray scattering, and cryo-transmission electron microscopy confirmed the presence of cubosomes or hexosomes, depending on the ratio between taurocholate and Span 80. Furthermore, the co-loaded nanoparticles exhibited high encapsulation efficiencies for both Ce6 and the coenzyme QH. In vitro studies on human melanoma cells (Me45) demonstrated the biocompatibility and photodynamic activity of the loaded formulations. These findings show the possibility of formulating more biocompatible cubosomes and hexosomes for photodynamic therapy in skin cancer treatment.
Assuntos
Melanoma , Nanopartículas , Neoplasias Cutâneas , Humanos , Melanoma/tratamento farmacológico , Melanoma/patologia , Nanopartículas/química , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Hexoses/química , Hexoses/farmacologia , Tamanho da Partícula , Clorofilídeos , Glicerídeos/química , Porfirinas/química , Porfirinas/farmacologia , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fotoquimioterapia , Sobrevivência Celular/efeitos dos fármacos , Ubiquinona/análogos & derivados , Ubiquinona/química , Ubiquinona/farmacologia , Ubiquinona/administração & dosagem , Linhagem Celular Tumoral , Propriedades de Superfície , Antineoplásicos/química , Antineoplásicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Ácido Taurocólico/químicaRESUMO
Transition metal-coordinated porphyrin metal-organic frameworks (MOFs) were perspective in photodynamic therapy (PDT) and catalytic therapy. However, the tumor hypoxia and the insufficient endogenous hydrogen peroxide (H2O2) seriously limited their efficacies. Herein, by encapsulating ultrasmall iridium (Ir) and modifying glucose oxidase (GOx), an iron-coordinated porphyrin MOF (Fe-MOF) nanoplatform (Fe-MOF@Ir/GOx) was designed to strengthen PDT/catalytic therapy by producing reactive oxygen species (ROS) storm. In this nanoplatform, Fe-MOF showed glutathione (GSH)-responsive degradation, by which porphyrin, GOx and ultrasmall Ir were released. Moreover, ultrasmall Ir possessed dual-activities of catalase (CAT)-like and peroxidase (POD)-like, which provided sufficient oxygen (O2) to enhance PDT efficacy, and hydroxyl radical (·OH) production was also improved by combining Fenton reaction of Fe2+. Further, GOx catalyzed endogenous glucose produced H2O2, also reduced pH value, which accelerated Fenton reaction and resulted in generation of ROS storm. Therefore, the developed Fe-MOF@Ir/GOx nanoplatform demonstrated enhanced PDT/catalytic therapy by producing ROS storm, and also provided a promising strategy to promote degradation/metabolism of inorganic nanoplatforms.
Assuntos
Glucose Oxidase , Irídio , Estruturas Metalorgânicas , Fotoquimioterapia , Porfirinas , Espécies Reativas de Oxigênio , Estruturas Metalorgânicas/química , Irídio/química , Espécies Reativas de Oxigênio/metabolismo , Catálise , Porfirinas/química , Humanos , Glucose Oxidase/química , Glucose Oxidase/metabolismo , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/metabolismo , Tamanho da Partícula , Propriedades de Superfície , Sobrevivência Celular/efeitos dos fármacosRESUMO
5-aminolevulinic acid photodynamic therapy (ALA-PDT) is an emerging therapeutic strategy for skin cancer due to its noninvasiveness and high spatiotemporal selectivity. However, poor skin penetration, poor intratumoral delivery, the instability of aqueous ALA, and the tumor's inherent hypoxia microenvironment are major hurdles hindering the efficacy of ALA-PDT. Herein, we aim to address these challenges by using microneedles (MNs) to assist in delivering nanoparticles based on natural polymeric tea polyphenols (TP NPs) to self-assemble and load ALA (ALA@TP NPs). The TP NPs specifically increase cellular uptake of ALA by A375 and A431 cells and reduce mitochondrial membrane potential. Subsequently, the photosensitizer protoporphyrin IX derived from ALA accumulates in the tumor cells in a dose-dependent manner with TP NPs, generating reactive oxygen species to promote apoptosis and necrosis of A375 and A431 cells. Interestingly, TP NPs can ameliorate the tumor's inherent hypoxia microenvironment and rapid oxygen consumption during PDT by inhibiting hypoxia inducible factor-1α, thereby boosting reactive oxygen species (ROS) generation and enhancing ALA-PDT efficacy through a positive feedback loop. After ALA@TP NPs are loaded into MNs to fabricate ALA@TP NPs@MNs, the MNs enhance skin penetration and storage stability of ALA. Importantly, they exhibit remarkable antitumor efficacy in A375-induced melanoma and A431-induced squamous cell carcinoma with a reduced dose of ALA and reverse hypoxia in vivo. This study provides a facile and novel strategy that integrates MNs and green NPs of TP for addressing the bottlenecks of ALA-PDT and enhancing the ALA-PDT efficacy against skin cancers for future clinical translation.
Assuntos
Ácido Aminolevulínico , Nanopartículas , Agulhas , Fotoquimioterapia , Fármacos Fotossensibilizantes , Polifenóis , Neoplasias Cutâneas , Chá , Ácido Aminolevulínico/química , Ácido Aminolevulínico/farmacologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Polifenóis/química , Polifenóis/farmacologia , Humanos , Nanopartículas/química , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Animais , Chá/química , Camundongos , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/administração & dosagem , Espécies Reativas de Oxigênio/metabolismo , Tamanho da Partícula , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Proliferação de Células/efeitos dos fármacos , Camundongos Nus , Propriedades de Superfície , Camundongos Endogâmicos BALB CRESUMO
While numerous methods exist for diagnosing tumors through the detection of miRNA within tumor cells, few can simultaneously achieve both tumor diagnosis and treatment. In this study, a novel graphene oxide (GO)-based DNA nanodevice (DND), initiated by miRNA, was developed for fluorescence signal amplification imaging and photodynamic therapy in tumor cells. After entering the cells, tumor-associated miRNA drives DND to Catalyzed hairpin self-assembly (CHA). The CHA reaction generated a multitude of DNA Y-type structures, resulting in a substantial amplification of Ce6 fluorescence release and the generation of numerous singlet oxygen (1O2) species induced by laser irradiation, consequently inducing cell apoptosis. In solution, DND exhibited high selectivity and sensitivity to miRNA-21, with a detection limit of 11.47 pM. Furthermore, DND discriminated between normal and tumor cells via fluorescence imaging and specifically generated O21 species in tumor cells upon laser irradiation, resulting in tumor cells apoptosis. The DND offer a new approach for the early diagnosis and timely treatment of malignant tumors.
Assuntos
DNA , Grafite , MicroRNAs , Fotoquimioterapia , Nanomedicina Teranóstica , Fotoquimioterapia/métodos , Humanos , MicroRNAs/análise , Grafite/química , Nanomedicina Teranóstica/métodos , DNA/química , Apoptose/efeitos dos fármacos , Imagem Óptica , Linhagem Celular Tumoral , Oxigênio Singlete/metabolismo , Oxigênio Singlete/química , Neoplasias/tratamento farmacológico , Neoplasias/diagnóstico por imagemRESUMO
Photodynamic therapy (PDT) is an appealing modality for cancer treatments. However, the limited tissue penetration depth of external-excitation light makes PDT impossible in treating deep-seated tumors. Meanwhile, tumor hypoxia and intracellular reductive microenvironment restrain the generation of reactive oxygen species (ROS). To overcome these limitations, a tumor-targeted self-illuminating supramolecular nanoparticle T-NPCe6-L-N is proposed by integrating photosensitizer Ce6 with luminol and nitric oxide (NO) for chemiluminescence resonance energy transfer (CRET)-activated PDT. The high H2O2 level in tumor can trigger chemiluminescence of luminol to realize CRET-activated PDT without exposure of external light. Meanwhile, the released NO significantly relieves tumor hypoxia via vascular normalization and reduces intracellular reductive GSH level, further enhancing ROS abundance. Importantly, due to the different ROS levels between cancer cells and normal cells, T-NPCe6-L-N can selectively trigger PDT in cancer cells while sparing normal cells, which ensured low side effect. The combination of CRET-based photosensitizer-activation and tumor microenvironment modulation overcomes the innate challenges of conventional PDT, demonstrating efficient inhibition of orthotopic and metastatic tumors on mice. It also provoked potent immunogenic cell death to ensure long-term suppression effects. The proof-of-concept research proved as a new strategy to solve the dilemma of PDT in treatment of deep-seated tumors.
Assuntos
Nanopartículas , Fotoquimioterapia , Fármacos Fotossensibilizantes , Microambiente Tumoral , Fotoquimioterapia/métodos , Microambiente Tumoral/efeitos dos fármacos , Animais , Nanopartículas/química , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Humanos , Camundongos , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo , Transferência de Energia , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Camundongos Endogâmicos BALB C , Luz , Camundongos Nus , Óxido Nítrico/metabolismoRESUMO
Photothermal therapy combined with chemotherapy has shown great promise in the treatment of cancer. In this synergistic system, a safe, stable, and efficient photothermal agent is desired. Herein, an effective photothermal agent, carbon quantum dots (CQDs), was initially synthesized and then rationally constructed a folic acid (FA)-targeted photothermal multifunctional nanoplatform by encapsulating CQDs and the anticancer drug doxorubicin (DOX) in the liposomes. Indocyanine green (ICG), a near infrared (NIR) photothermal agent, approved by the U.S. Food and Drug Administration, was embedded in the bilayer membrane to further enhance the photothermal effects and facilitate the rapid cleavage of liposomes for drug release. Triggered by the NIR laser, this engineered photothermal multifunctional nanoplatform, not only exhibited an excellent performance with the photothermal conversion efficiency of up to 47.14%, but also achieved controlled release of the payloads. In vitro, and in vivo experiments demonstrated that the photothermal multifunctional nanoplatform had excellent biocompatibility, enhanced tumor-specific targeting, stimuli-responsive drug release, effective cancer cell killing and tumor suppression through multi-modal synergistic therapy. The successful construction of this NIR light-triggered targeted photothermal multifunctional nanoplatform will provide a promising strategy for the design and development of synergistic chemo-photothermal combination therapy and improve the therapeutic efficacy of cancer treatment.
Assuntos
Carbono , Doxorrubicina , Terapia Fototérmica , Pontos Quânticos , Doxorrubicina/farmacologia , Doxorrubicina/química , Humanos , Pontos Quânticos/química , Animais , Camundongos , Carbono/química , Carbono/farmacologia , Verde de Indocianina/química , Verde de Indocianina/farmacologia , Ácido Fólico/química , Ácido Fólico/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Lipossomos/química , Tamanho da Partícula , Ensaios de Seleção de Medicamentos Antitumorais , Antineoplásicos/farmacologia , Antineoplásicos/química , Raios Infravermelhos , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/administração & dosagem , Propriedades de Superfície , Proliferação de Células/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Neoplasias Experimentais/patologia , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/terapia , Nanopartículas/químicaRESUMO
This study assessed the SARS-CoV-2 surrogate bacteriophage φ6 cross-contamination between high-density polyethylene or polyvinyl chloride gloves and fruits (tomato and cucumber) using different inoculum levels (6.0 and 4.0 log PFU/sample). Bacteriophage φ6 survival on contaminated gloves was assessed over 9 days at 25 °C. The effectiveness of photodynamic treatment using curcumin as a photosensitizer to inactivate φ6 on fruits was determined. The fruit type and the glove material influenced the φ6 transfer. Longer contact times resulted in greater φ6 transfer. The highest φ6 transfer occurred from tomato to HDPE glove (0.8% or -1.1 log % transfer) after 30 s of contact at the higher inoculum level. Bacteriophage φ6 was detected on cross-contaminated HDPE gloves for up to 6 days. Bacteriophage φ6 survived better on vinyl gloves cross-contaminated by cucumber vs. tomato (detected up to 6 vs 3 days). Photodynamic inactivation of φ6 was time-dependent and varied with the tested fruit but was not influenced by viral starting concentration. Photodynamic treatment decreased the φ6 titer by 3.0 and 2.2 log PFU/sample in tomato and cucumber, respectively. Transmission electronic microscopy showed that photodynamic treatment changed the structure of the φ6 capsid. These findings may help in the management of SARS-CoV-2 contamination risks in fruit handling. They may also help in the establishment of effective measures to manage cross-contamination risk.
Assuntos
Bacteriófago phi 6 , COVID-19 , Cucumis sativus , Frutas , Fármacos Fotossensibilizantes , SARS-CoV-2 , Solanum lycopersicum , SARS-CoV-2/efeitos dos fármacos , Frutas/virologia , Solanum lycopersicum/virologia , COVID-19/virologia , Bacteriófago phi 6/efeitos dos fármacos , Bacteriófago phi 6/fisiologia , Bacteriófago phi 6/crescimento & desenvolvimento , Cucumis sativus/virologia , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Inativação de Vírus/efeitos dos fármacos , Inativação de Vírus/efeitos da radiação , Luvas Protetoras , Humanos , Curcumina/farmacologia , Curcumina/químicaRESUMO
Photodynamic therapy (PDT) employs reactive oxygen species (ROS) from a photosensitizer (PS) under light, inhibiting multi-drug resistance in bacteria. However, hypoxic conditions in infection sites and biofilms challenge PDT efficiency. We developed fluorinated small molecular micelles (PF-CBMs) as PS carriers to address this, relieving hypoxia and enhancing PS penetration into biofilms. Perfluorocarbons in PF-CBMs transport more oxygen due to their excellent oxygen-dissolving capability. Fluorination enhances loading capacity and serum stability, reduces premature release, and improves cellular uptake, to improve PDT efficacy. PF-CBMs, with acid-induced surface charge transformation, exhibit superior biofilm penetration, resulting in increased antibiofilm activity of PDT. Compared to fluorine-free micelles (PC-CBMs), PF-CBMs demonstrate better serum stability, higher drug loading, and reduced premature release, leading to significantly improved antibacterial efficacy in vitro and in vivo. In conclusion, fluorinated micelles with surface charge reversal enhance PDT for antibacterial and antibiofilm applications.
Assuntos
Antibacterianos , Biofilmes , Halogenação , Micelas , Fotoquimioterapia , Fármacos Fotossensibilizantes , Propriedades de Superfície , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Antibacterianos/farmacologia , Antibacterianos/química , Biofilmes/efeitos dos fármacos , Animais , Camundongos , Testes de Sensibilidade Microbiana , Fluorocarbonos/química , Fluorocarbonos/farmacologia , Humanos , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Tamanho da Partícula , Infecções Bacterianas/tratamento farmacológicoRESUMO
Photodynamic therapy (PDT) and catalytic therapy were promising treatment modes, but tumor hypoxia and poor catalytic activity severely limited their efficacies. Herein, using a porphyrin metal-organic framework (PCN-224) as nanocarrier, a platinum/palladium (Pt/Pd) dual-modified PCN-224 nanoprobe (PCN-224-Pt@Pd) with strong peroxidase (POD)/catalase (CAT)-like activities was developed, achieving photothermal-promoted PDT/catalytic therapy. Compared with single ultrasmall Pt modifying, CAT-like activity of Pt/Pd dual-modifying increased oxygen concentration from 6.24 to 9.35 mg/L, which improved singlet oxygen (1O2) yield from 63.8 % to 82.9 %. Moreover, POD-like activity of Pt/Pd dual-modifying significantly accelerated hydroxyl radicals (·OH) generation. Importantly, PCN-224-Pt@Pd possessed near-infrared II (NIR-II) photothermal effect with a high efficiency (55.6 %), which further promoted ·OH production. Under combined therapy of PCN-224-Pt@Pd, the cell survival rate greatly reduced to 5.8 %, and the tumors were cured, suggesting NIR-II photothermal-enhanced PDT/catalytic therapy.
Assuntos
Raios Infravermelhos , Estruturas Metalorgânicas , Paládio , Fotoquimioterapia , Fármacos Fotossensibilizantes , Platina , Porfirinas , Paládio/química , Paládio/farmacologia , Platina/química , Platina/farmacologia , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Catálise , Porfirinas/química , Porfirinas/farmacologia , Humanos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Camundongos , Antineoplásicos/química , Antineoplásicos/farmacologia , Tamanho da Partícula , Propriedades de Superfície , Ensaios de Seleção de Medicamentos Antitumorais , Proliferação de Células/efeitos dos fármacosRESUMO
Photodynamic therapy (PDT) is an alternative to cancer treatment, demonstrating selectivity and significant cytotoxicity on malignant tissues. Such therapy involves two nontoxic components: photosensitizer (PS) and non-ionizing radiation. In optimal dosage combinations, PDT causes cellular and tissue effects by oxygen-dependent processes, leading tumor cells to regulated cell death pathways. Regulated necrosis, called necroptosis, can be triggered by PDT and is characterized by caspase-8 inhibition and RIPK1, RIPK3, and MLKL activities, leading to plasma membrane pores formation with subsequent cellular content release into the extracellular space. For this review, studies accessed by PubMed describing the relation between necroptosis and PDT were summarized. The results showed that PDT can trigger necroptosis mechanisms in different tumor cells. Moreover, a mix of different cell death types can co-occur. It is also important to highlight that necroptosis triggered by PDT is related to damage-associated molecular patterns (DAMPs) release, involving immunogenic cell death and vaccination. The cell death response is directly related to the photosensitizer chemical characteristics, concentration, incubation time, cellular location, and irradiation parameters. The synergism among all cell death types is an excellent advantage for avowing tumor resistance mechanisms and developing new solutions.
Assuntos
Necroptose , Neoplasias , Fotoquimioterapia , Fármacos Fotossensibilizantes , Fotoquimioterapia/métodos , Humanos , Necroptose/efeitos dos fármacos , Necroptose/efeitos da radiação , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , AnimaisRESUMO
The cyanine dyes represented by IR780 can achieve synergistic photodynamic therapy (PDT) and photothermal therapy (PTT) under the stimulation of near-infrared (NIR) light (commonly 808 nm). Unfortunately, the stability of NIR-excited cyanine dyes is not satisfactory. These cyanine dyes can be attacked by self-generated reactive oxygen species (ROS) during PDT processes, resulting in structural damage and rapid degradation, which is fatal for phototherapy. To address this issue, a novel non-cyanine dye (IR890) was elaborately designed and synthesized by our team. The maximum absorption wavelength of IR890 was located in the deep NIR region (ca. 890 nm), which was beneficial for further improving tissue penetration depth. Importantly, IR890 exhibited good stability when continuously illuminated by deep NIR light. To improve the hydrophilicity and biocompatibility, the hydrophobic IR890 dye was grafted onto the side chain of hydrophilic polymer (POEGMA-b-PGMA-g-C[bond, triple bond]CH) via click chemistry. Then, the synthesized POEGMA-b-PGMA-g-IR890 amphiphilic polymer was utilized to prepare P-IR890 nano-photosensitizer via self-assembly method. Under irradiation with deep NIR light (850 nm, 0.5 W/cm2, 10 min), the dye degradation rate of P-IR890 was less than 5%. However, IR780 was almost completely degraded with the same light output power density and irradiation duration. In addition, P-IR890 could stably generate a large number of ROS and heat at the same time. It was rarely reported that the stable synergistic combination therapy of PDT and PTT could be efficiently performed by a single photosensitizer via irradiation with deep NIR light. P-IR890 exhibited favorable anti-tumor outcomes through apoptosis pathway. Therefore, the P-IR890 could provide a new insight into the design of photosensitizers and new opportunities for synergistic combination therapy of PDT and PTT.
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Several reports are available on aggregation-induced emission and its applications in biomedical imaging and other material sciences. However, enhancement of singlet oxygen generation in nanoaggregates is rarely reported. Here, we report the synthesis of Naph-BODIPY Br2, which absorbs at 661 nm (monomer) with a high molar absorption coefficient. The presence of bromine promotes intersystem crossing, thereby enhancing the singlet oxygen quantum yield (ΦΔ â¼ 0.50 in methanol). In order to increase hydrophilicity, we developed Naph-BODIPY Br2 nanoaggregates (â¼100 nm), which demonstrated aggregation-induced properties and exhibited a bathochromic shift with an absorption maximum at 757 nm. The bathochromic shift in the UV-vis spectra due to aggregation is corroborated by TD-DFT analysis. The computational data also confirm the presence of a low-lying triplet state, which enhances the generation of singlet oxygen, making it effective for photodynamic therapy. These aggregates showed excellent singlet oxygen generation in aqueous media, compared to their monomeric form and standard methylene blue. Their hydrophilic nature and high singlet oxygen generation enabled significant phototoxicity against human carcinoma cells with IC50 values of 4.06 ± 0.01 and 4.09 ± 0.1 µM, respectively, for MCF-7 and A549 cells upon 5 min exposure to light. Moreover, their phototoxicity further increases with an increasing exposure time of light for both cell lines. Notably, Naph-BODIPY Br2 nanoaggregates exhibited nearly zero dark cell toxicity and effectively induced apoptosis in cancer cells upon light activation, highlighting their potential as powerful photosensitizers for photodynamic cancer therapy.
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Water pollution is a significant concern worldwide, and it includes contaminants such as antibiotic-resistant pathogens. Antimicrobial photodynamic therapy (aPDT) offers a non-invasive and non-toxic alternative for the inactivation of these microorganisms. So, this study reports the synthesis, structural characterisation, photophysical properties, and aPDT efficacy of cationic free-base and zinc(II) chlorin (Chl) derivatives bearing N,N-dimethylpyrrolydinium groups (H2Chl 1a and ZnChl 1b). The aPDT assays were performed against two bacterial models: Staphylococcus aureus (Gram-(+)) and Escherichia coli (Gram-(-)). The H2Chl 1a and ZnChl 1b distinct's solubility profile, coupled with their ability to generate singlet oxygen (1O2) under light exposure, (H2Chl 1a, Ð¤Δ = 0.58 < TPP, Ð¤Δ = 0.65 < ZnChl 1b, Ð¤Δ = 0.83) opens up their potential application as photosensitizers (PS) in aPDT. The effectiveness of H2Chl 1a and ZnChl 1b at 1.0 and 5.0 µM in aPDT against S. aureus and E. coli at 500 W m-2 (total exposure time: 60-120 min) showed a viability reduction >6.0 log10 CFU mL-1. Additionally, KI was used as a coadjuvant to potentiate the photoinactivation of E. coli, reaching the method's detection limit (>4.0 log10 RLU). As most of the PS developed to inactivate Gram-negative bacteria are cationic with three or more charges, the fact that the H2Chl 1a and ZnChl 1b with only one cationic charge photoinactivate E. coli at low concentrations and with a reduced light dose, it is an importing discovery that deserves further exploration. These monocharged chlorin dyes have the potential for water remediation.
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Photodynamic therapy (PDT) utilizing metal-organic frameworks (MOFs) has developed as a new and efficacious treatment for malignant tumors located on the surface of the human body. In order to achieve more effective PDT treatment outcomes, the traditional method has been to increase the intensity of the laser irradiation, but this approach can easily lead to tissue burns. In this study, we developed a new type of nanoparticle, F68-PKI@PCN224, aims to achieve effective PDT upon medullary thyroid carcinoma (MTC) which is an uncommon form of thyroid cancer that originates in the parafollicular cells of the thyroid and the therapeutic outlook for patients with MTC remains unsatisfactory. F68-PKI@PCN224 combines the antitumor features of PDT with mammalian target of rapamycin (mTOR) inhibitor PKI-587 (PKI). The tumor sensitization, slow release, and pH response features of F68-PKI@PCN224 was demonstrated by a series of in vitro and in vivo experiments / assays. F68-PKI@PCN224 achieved the long-term activation and slow releasing of PKI and TCPP in MTC tumor tissues. During the process of generating PDT effects, F68-PKI@PCN224 enhanced the tumor's sensitivity to PDT, direct laser irradiation of MTC cells or subcutaneous tumor tissues. As a result, low-dose phototherapy achieves a higher anti-tumor effect upon F68-PKI@PCN224 compared with TCPP. This study reveals the synergistic effect between tumor sensitization by mTOR inhibitor and PDT and initially unveils the mechanism of action of these nanoparticles.
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Background: Phototherapy based on photocatalytic semiconductor nanomaterials has received considerable attention for the cancer treatment. Nonetheless, intense efficacy for in vivo treatment is restricted by inadequate photocatalytic activity and visible light response. Methods: In this study, we designed a photocatalytic heterostructure using graphitic carbon nitride (g-C3N4) and tin disulfide (SnS2) to synthesize g-C3N4/SnS2 heterostructure through hydrothermal process. Furthermore, Au nanoparticles were decorated in situ deposition on the surface of the g-C3N4/SnS2 heterostructure to form g-C3N4/SnS2@Au nanoparticles. Results: The g-C3N4/SnS2@Au nanoparticles generated intense reactive oxygen species radicals under near-infrared (NIR) laser irradiation through photodynamic therapy (PDT) pathways (Type-I and Type-II). These nanoparticles exhibited enhanced photothermal therapy (PTT) efficacy with high photothermal conversion efficiency (41%) when subjected to 808 nm laser light, owing to the presence of Au nanoparticles. The in vitro studies have indicated that these nanoparticles can induce human liver carcinoma cancer cell (HepG2) apoptosis (approximately 80% cell death) through the synergistic therapeutic effects of PDT and PTT. The in vivo results demonstrated that these nanoparticles exhibited enhanced efficient antitumor effects based on the combined effects of PDT and PTT. Conclusion: The g-C3N4/SnS2@Au nanoparticles possessed enhanced photothermal properties and PDT effect, good biocompatibility and intense antitumor efficacy. Therefore, these nanoparticles could be considered promising candidates through synergistic PDT/PTT effects upon irradiation with NIR laser for cancer treatment.
Assuntos
Ouro , Grafite , Raios Infravermelhos , Nanopartículas Metálicas , Fotoquimioterapia , Terapia Fototérmica , Ouro/química , Humanos , Fotoquimioterapia/métodos , Terapia Fototérmica/métodos , Animais , Nanopartículas Metálicas/química , Células Hep G2 , Camundongos , Grafite/química , Compostos de Nitrogênio/química , Espécies Reativas de Oxigênio/metabolismo , Apoptose/efeitos dos fármacos , Neoplasias Hepáticas/terapia , Camundongos Endogâmicos BALB C , Sulfetos/química , Sulfetos/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Camundongos NusRESUMO
Graphite carbon nitride (CN) eliminates cancer cells by converting H2O2 to highly toxic â¢OH under visible light. However, its in vivo applications are constrained by insufficient endogenous H2O2, accumulation of OH- and finite photocarriers. We designed Fe/NV-CN, co-modified CN with nitrogen vacancies (NV) and ferric ions (Fe3+). NV and Fe3+, not only adjust the band structure of CN through quantum confinement effect and the altered coupled oscillations of atomic orbitals to facilitates â¢OH production by oxidizing OH-, but also construct dual carrier-transfer channels for electrons and holes to respective active sites by introducing stepped electrostatic potential and shortening three-electron bonds, thereby involving more carriers in â¢OH production. Fe/NV-CN, the novel reactor, effectually produces vast â¢OH under illumination by expanding OH- as the raw material of â¢OH and augmenting carriers at active sites, which induces cancer cell apoptosis by disrupting mitochondrial function for significant shrinkage of Cal27 cell-induced tumor under illumination. This work provides not only an effective photosensitizer avoiding the accumulation of OH- for cancer therapy but also a novel strategy by constructing dual carrier-transfer channels on semiconductor photosensitizers for improving the therapeutic effect of photodynamic therapy.
RESUMO
This study evaluates the efficacy of photodynamic therapy (PDT) in treating central serous chorioretinopathy (CSC) based on the number of engorged vortex vein draining macula visualized on ultra-widefield (UWF) indocyanine green angiography (ICGA). Thirty-six eyes of 36 patients with treatment-naïve CSC were included. Macula-draining vortex veins were assessed in each quadrant using UWF ICGA. The resolution of subretinal fluid (SRF), pigment epithelial detachment (PED), ellipsoid zone (EZ) disintegrity, and retinal pigment epithelium (RPE) irregularity were evaluated at 3 months after PDT. Visual and anatomical improvements were monitored for 12 months. Logistic regression analysis was performed to identify factors associated with poor visual outcomes. A higher number of macula-draining vortex vein was associated to persistent SRF (p = 0.004), PED (p = 0.001), EZ disintegrity (p = 0.011), and RPE irregularity (p = 0.001). Macula-draining vortex veins were also correlated with poor EZ restoration and limited best corrected visual acuity (BCVA) improvements. In multivariate analysis, the number of macula-draining vortex vein (B = 0.197, p = 0.047) was a risk factor for worse BCVA at 12 months. Increased macula-draining vortex vein was related with unfavorable anatomical and poor visual outcomes after PDT in CSC patients.
Assuntos
Coriorretinopatia Serosa Central , Fotoquimioterapia , Acuidade Visual , Humanos , Coriorretinopatia Serosa Central/tratamento farmacológico , Coriorretinopatia Serosa Central/diagnóstico por imagem , Fotoquimioterapia/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Acuidade Visual/efeitos dos fármacos , Angiofluoresceinografia , Resultado do Tratamento , Epitélio Pigmentado da Retina/diagnóstico por imagem , Epitélio Pigmentado da Retina/patologia , Epitélio Pigmentado da Retina/efeitos dos fármacos , Macula Lutea/irrigação sanguínea , Macula Lutea/diagnóstico por imagem , Tomografia de Coerência Óptica , Verde de Indocianina , Líquido Sub-Retiniano/efeitos dos fármacosRESUMO
Organic luminogens with dual-state emission (DSE) have garnered widespread attention due to their versatility in the forms of both dilute solutions and solids. Despite the growing interest, most research on DSE focuses primarily on molecule design and photophysical investigation, with limited exploration of their practical applications. In this study, we introduce a novel fluorescent molecule, PCT, featuring a distinct D-π(A)-D' electronic structure. PCT exhibited efficient DSE properties, with high quantum yields in both dilute solutions (ΦTHF = 52.3 %) and solid-state (Φsolid = 74.6 %). Taking advantage of PCT's lipophilicity, we demonstrated its potential for targeted lipid droplet (LD) imaging in living cells and its utility in monitoring LD depletion during cellular starvation. To further enhance its applicability in photodynamic therapy (PDT), PCT was encapsulated within the amphiphilic triblock copolymer Pluronic F127, forming PCT@F127 nanoparticles with improved colloidal stability. These nanoparticles efficiently generated singlet oxygen (1O2) under white light irradiation, achieving a 1O2 quantum yield of 57.2 %. In vitro studies on MCF-7 cells revealed significant 1O2 generation and potent phototoxicity, leading to marked cell apoptosis and necrosis. These results underscore PCT's multifunctionality as a DSEgen, with promising applications in both bioimaging and PDT.
RESUMO
Photodynamic Therapy (PDT) has emerged as a highly efficient and non-invasive cancer treatment, which is crucial considering the significant global mortality rates associated with cancer. The effectiveness of PDT primarily relies on the quality of the photosensitizers employed. When exposed to appropriate light irradiation, these photosensitizers absorb energy and transition to an excited state, eventually transferring energy to nearby molecules and generating Reactive Oxygen Species (ROS), including singlet oxygen [1O2]. The ability to absorb light in visible and nearinfrared wavelengths makes porphyrins and derivatives useful photosensitizers for PDT. Chemically, Porphyrins, composed of tetra-pyrrole structures connected by four methylene groups, represent the typical photosensitizers. The limited water solubility and bio-stability of porphyrin photosensitizers and their non-specific tumor-targeting properties hinder PDT effectiveness and clinical applications. Therefore, a wide range of modification and functionalization techniques have been used to maximize PDT efficiency and develop multidimensional porphyrin-based functional materials. Recent progress in porphyrin-based functional materials has been investigated in this review paper, focusing on two main aspects including the development of porphyrinic amphiphiles that improve water solubility and biocompatibility, and the design of porphyrin-based polymers, including block copolymers with covalent bonds and supramolecular polymers with noncovalent bonds, which provide versatile platforms for PDT applications. The development of porphyrin-based functional materials will allow researchers to significantly expand PDT applications for cancer therapy by opening up new opportunities. With these innovations, porphyrins will overcome their limitations and push PDT to the forefront of cancer treatment options.