RESUMO
The accumulation of photosensitizers (PSs) in lesion sites but not in other organs is an important challenge for efficient image guiding in photodynamic therapy. Cancer cells are known to express a significant number of albumin-binding proteins that take up albumin as a nutrient source. Here, we converted albumin to a novel BODIPY-like PS by generating a tetrahedral boron environment via a flick reaction. The formed albumin PS has almost the same 3-dimensional structural feature as free albumin because binding occurs at Sudlow Site 1, which is located in the interior space of albumin. An i.v. injection experiment in tumor-bearing mice demonstrated that the human serum albumin PS effectively accumulated in cancer tissue and, more surprisingly, albumin PS accumulated much more in the cancer tissue than in the liver and kidneys. The albumin PS was effective at killing tumor cells through the generation of reactive oxygen species under light irradiation. The crystal structure of the albumin PS was fully elucidated by X-ray crystallography; thus, further tuning of the structure will lead to novel physicochemical properties of the albumin PS, suggesting its potential in biological and clinical applications.
Assuntos
Compostos de Boro , Fotoquimioterapia , Fármacos Fotossensibilizantes , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fotoquimioterapia/métodos , Animais , Compostos de Boro/química , Humanos , Camundongos , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB C , Espécies Reativas de Oxigênio/metabolismo , Camundongos Nus , Albuminas/química , Albuminas/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/metabolismoRESUMO
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
The notorious tumor microenvironment (TME) usually becomes more deteriorative during phototherapeutic progress that hampers the antitumor efficacy. To overcome this issue, we herein report the ameliorative and adaptive nanoparticles (TPASIC-PFH@PLGA NPs) that simultaneously reverse hypoxia TME and switch photoactivities from photothermal-dominated state to photodynamic-dominated state to maximize phototherapeutic effect. TPASIC-PFH@PLGA NPs are designed by incorporating oxygen-rich liquid perfluorohexane (PFH) into the intraparticle microenvironment to regulate the intramolecular motions of AIE photosensitizer TPASIC. TPASIC exhibits a unique aggregation-enhanced reactive oxygen species (ROS) generation feature. PFH incorporation affords TPASIC the initially dispersed state, thus promoting active intramolecular motions and photothermal conversion efficiency. While PFH volatilization leads to nanoparticle collapse and the formation of tight TPASIC aggregates with largely enhanced ROS generation efficiency. As a consequence, PFH incorporation not only currently promotes both photothermal and photodynamic efficacies of TPASIC and increases the intratumoral oxygen level, but also enables the smart photothermal-to-photodynamic switch to maximize the phototherapeutic performance. The integration of PFH and AIE photosensitizer eventually delivers more excellent antitumor effect over conventional phototherapeutic agents with fixed photothermal and photodynamic efficacies. This study proposes a new nanoengineering strategy to ameliorate TME and adapt the treatment modality to fit the changed TME for advanced antitumor applications.
Assuntos
Fluorocarbonos , Nanopartículas , Fotoquimioterapia , Fármacos Fotossensibilizantes , Espécies Reativas de Oxigênio , Microambiente Tumoral , Nanopartículas/química , Microambiente Tumoral/efeitos dos fármacos , Animais , Fotoquimioterapia/métodos , Espécies Reativas de Oxigênio/metabolismo , Fluorocarbonos/química , Fluorocarbonos/farmacologia , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Humanos , Camundongos , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Camundongos Endogâmicos BALB C , Terapia Fototérmica/métodos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Fototerapia/métodos , FemininoRESUMO
Immunosuppressive tumor microenvironment (ITM) severely limited the efficacy of immunotherapy against triple-negative breast cancer (TNBC). Herein, Apt-LPR, a light-activatable photodynamic therapy (PDT)/RNAi immune synergy-enhancer was constructed by co-loading miR-34a and photosensitizers in cationic liposomes (in phase III clinical trial). Interestingly, the introduction of tumor-specific aptamers creates a special "Liposome-Aptamer-Target" interface, where the aptamers are initially in a "lying down" state but transform to "standing up" after target binding. The interfacing mechanism was elaborately revealed by computational and practical experiments. This unique interface endowed Apt-LPR with neutralized surface potential of cationic liposomes to reduce non-specific cytotoxicity, enhanced DNase resistance to protect aptamers, and preserved target-binding ability for selective drug delivery. Upon near-infrared irradiation, the generated reactive oxygen species would oxidize unsaturated phospholipids to destabilize both liposomes and lysosomes, realizing stepwise lysosomal escape of miR-34a for tumor cell apoptosis and downregulation of PD-L1 to suppress immune escape. Together, tumor-associated antigens released from PDT-damaged mitochondria and endoplasmic reticulum could activate the suppressive immune cells to establish an "immune hot" milieu. The collaborative immune-enhancing strategy effectively aroused systemic antitumor immunity and inhibited primary and distal tumor progression as well as lung metastasis in 4T1 xenografted mouse models. The photo-controlled drug release and specific tumor-targeting capabilities of Apt-LPR were also visualized in MDA-MB-231 xenografted zebrafish models. Therefore, this photoswitchable PDT/RNAi immune stimulator offered a powerful approach to reprogramming ITM and reinforcing cancer immunotherapy efficacy.
Assuntos
Lipossomos , MicroRNAs , Fotoquimioterapia , Fármacos Fotossensibilizantes , Neoplasias de Mama Triplo Negativas , Microambiente Tumoral , Animais , Humanos , Lipossomos/química , MicroRNAs/genética , MicroRNAs/metabolismo , Fotoquimioterapia/métodos , Microambiente Tumoral/efeitos dos fármacos , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Feminino , Neoplasias de Mama Triplo Negativas/terapia , Neoplasias de Mama Triplo Negativas/patologia , Camundongos , Aptâmeros de Nucleotídeos/química , Preparações de Ação Retardada/química , Interferência de RNA , Peixe-ZebraRESUMO
Stimulator of interferon genes (STING) agonists have shown promise in cancer treatment by stimulating the innate immune response, yet their clinical potential has been limited by inefficient cytosolic entry and unsatisfactory pharmacological activities. Moreover, aggressive tumors with "cold" and immunosuppressive microenvironments may not be effectively suppressed solely through innate immunotherapy. Herein, we propose a multifaceted immunostimulating nanoparticle (Mn-MC NP), which integrates manganese II (Mn2+) coordinated photosensitizers (chlorin e6, Ce6) and STING agonists (MSA-2) within a PEGylated nanostructure. In Mn-MC NPs, Ce6 exerts potent phototherapeutic effects, facilitating tumor ablation and inducing immunogenic cell death to elicit robust adaptive antitumor immunity. MSA-2 activates the STING pathway powered by Mn2+, thereby promoting innate antitumor immunity. The Mn-MC NPs feature a high drug-loading capacity (63.42 %) and directly ablate tumor tissue while synergistically boosting both adaptive and innate immune responses. In subsutaneous tumor mouse models, the Mn-MC NPs exhibit remarkable efficacy in not only eradicating primary tumors but also impeding the progression of distal and metastatic tumors through synergistic immunotherapy. Additionally, they contribute to preventing tumor recurrence by fostering long-term immunological memory. Our multifaceted immunostimulating nanoparticle holds significant potential for overcoming limitations associated with insufficient antitumor immunity and ineffective cancer treatment.
Assuntos
Imunoterapia , Manganês , Nanopartículas , Animais , Imunoterapia/métodos , Manganês/química , Nanopartículas/química , Camundongos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Linhagem Celular Tumoral , Humanos , Porfirinas/química , Porfirinas/farmacologia , Clorofilídeos , Neoplasias/terapia , Neoplasias/imunologia , Fotoquimioterapia/métodos , Imunidade Inata/efeitos dos fármacos , Feminino , Camundongos Endogâmicos C57BL , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/químicaRESUMO
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
The biofilm-induced "relatively immune-compromised zone" creates an immunosuppressive microenvironment that is a significant contributor to refractory infections in orthopedic endophytes. Consequently, the manipulation of immune cells to co-inhibit or co-activate signaling represents a crucial strategy for the management of biofilm. This study reports the incorporation of Mn2+ into mesoporous dopamine nanoparticles (Mnp) containing the stimulator of interferon genes (STING) pathway activator cGAMP (Mncp), and outer wrapping by M1-like macrophage cell membrane (m-Mncp). The cell membrane enhances the material's targeting ability for biofilm, allowing it to accumulate locally at the infectious focus. Furthermore, m-Mncp mechanically disrupts the biofilm through photothermal therapy and induces antigen exposure through photodynamic therapy-generated reactive oxygen species (ROS). Importantly, the modulation of immunosuppression and immune activation results in the augmentation of antigen-presenting cells (APCs) and the commencement of antigen presentation, thereby inducing biofilm-specific humoral immunity and memory responses. Additionally, this approach effectively suppresses the activation of myeloid-derived suppressor cells (MDSCs) while simultaneously boosting the activity of T cells. Our study showcases the efficacy of utilizing m-Mncp immunotherapy in conjunction with photothermal and photodynamic therapy to effectively mitigate residual and recurrent infections following the extraction of infected implants. As such, this research presents a viable alternative to traditional antibiotic treatments for biofilm that are challenging to manage.
Assuntos
Biofilmes , Indóis , Proteínas de Membrana , Polímeros , Biofilmes/efeitos dos fármacos , Polímeros/química , Animais , Indóis/química , Indóis/farmacologia , Camundongos , Proteínas de Membrana/metabolismo , Nanopartículas/química , Fotoquimioterapia/métodos , Porosidade , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Feminino , Transdução de Sinais/efeitos dos fármacos , Terapia Fototérmica , Células Supressoras Mieloides/metabolismo , Células Supressoras Mieloides/efeitos dos fármacos , Camundongos Endogâmicos C57BLRESUMO
Human papillomavirus (HPV) infection can cause condyloma acuminatum (CA), which is characterized by a high incidence and a propensity for recurrence after treatment. Angiogenesis plays an important role in the occurrence and development of CA. Seryl-tRNA synthetase (SerRS) is a newly identified, potent anti-angiogenic factor that directly binds to the vascular endothelial growth factor (VEGFA) promoter, thereby suppressing its transcription. Emodin is a natural anthraquinone derivative that can promote SerRS expression. This study aimed to investigate the effects of emodin on CA and explore combined treatment strategies. The HPV-infected cell line SiHa was treated with either DMSO, emodin, ALA-PDT or a combination of emodin and ALA-PDT. We observed the effects on cell proliferation, apoptosis and the SerRS-VEGFA pathway. Our findings demonstrated that emodin targets angiogenesis through the SerRS-VEGFA pathway, resulting in the inhibition of SiHa cell proliferation and promotion of apoptosis (p < 0.001). To verify the therapeutic effect of emodin combined with ALA-PDT on HPV-associated tumours in vivo, we established an animal xenograft model by subcutaneously inoculating mice with SiHa cells (n = 4). The results showed that the combination of emodin and ALA-PDT significantly inhibited the expression of VEGFA to inhibit angiogenesis (p < 0.001), thus showing an inhibitory effect on tumour (p < 0.001). Furthermore, we determined that the mechanism underlying the decrease in VEGFA expression after emodin combined with ALA-PDT in CA may be attributed to the promotion of SerRS expression (p < 0.001). The combination of emodin and ALA-PDT holds promise as a novel therapeutic target for CA by targeting neovascularization in condyloma tissues.
Assuntos
Ácido Aminolevulínico , Apoptose , Proliferação de Células , Condiloma Acuminado , Emodina , Neovascularização Patológica , Fotoquimioterapia , Fator A de Crescimento do Endotélio Vascular , Emodina/farmacologia , Emodina/uso terapêutico , Humanos , Animais , Condiloma Acuminado/tratamento farmacológico , Condiloma Acuminado/virologia , Condiloma Acuminado/patologia , Proliferação de Células/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/metabolismo , Fotoquimioterapia/métodos , Camundongos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Ácido Aminolevulínico/farmacologia , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Nus , Camundongos Endogâmicos BALB C , Feminino , AngiogêneseRESUMO
BACKGROUND: Therapeutic approaches that combine conventional photodynamic therapy (PDT) with gas therapy (GT) to sensitize PDT are an attractive strategy, but the molecular structure design of the complex lacks effective guiding strategies. RESULTS: Herein, we have developed a nanoplatforms Cy-NMNO@SiO2 based on mesoporous silica materials loaded NIR-activatable small-molecule fluorescent probe Cy-NMNO for the synergistic treatment of photodynamic therapy/gas therapy (PDT/GT) in antibacterial and skin cancer. The theoretical calculation results showed that the low dissociation of N-NO in Cy-NMNO enabled it to dissociate effectively under NIR light irradiation, which is conducive to produce Cy and NO. Cy showed better 1O2 generation performance than Cy-NMNO. The cytotoxicity of Cy-NMNO obtained via the synergistic effect of GT and PDT synergistically enhances the effect of photodynamic therapy, thus achieving more effective tumor treatment and sterilization than conventional PDT. Moreover, the nanoplatforms Cy-NMNO@SiO2 realized efficient drug loading and drug delivery. CONCLUSIONS: This work not only offers a promising approach for PDT-GT synergistic drug delivery system, but also provides a valuable reference for the design of its drug molecules.
Assuntos
Nanopartículas , Óxido Nítrico , Fotoquimioterapia , Fármacos Fotossensibilizantes , Dióxido de Silício , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Nanopartículas/química , Óxido Nítrico/química , Óxido Nítrico/metabolismo , Humanos , Dióxido de Silício/química , Animais , Camundongos , Linhagem Celular Tumoral , Raios Infravermelhos , Sistemas de Liberação de Medicamentos/métodos , Neoplasias Cutâneas/tratamento farmacológico , Antibacterianos/farmacologia , Antibacterianos/química , Sobrevivência Celular/efeitos dos fármacos , Camundongos Endogâmicos BALB CRESUMO
Breast cancer therapy has significantly advanced by targeting the programmed cell death-ligand 1/programmed cell death-1 (PD-L1/PD-1) pathway. BMS-202 (a smallmolecule PD-L1 inhibitor) induces PD-L1 dimerization to block PD-1/PD-L1 interactions, allowing the T-cell-mediated immune response to kill tumor cells. However, immunotherapy alone has limited effects. Clinically approved photodynamic therapy (PDT) activates immunity and selectively targets malignant cells. However, PDT aggravates hypoxia, which may compromise its therapeutic efficacy and promote tumor metastasis. We designed a tumor-specific delivery nanoplatform of liposomes that encapsulate the hypoxia-sensitive antitumor drug tirapazamine (TPZ) and the small-molecule immunosuppressant BMS. New indocyanine green (IR820)-loaded polyethylenimine-folic acid (PEI-FA) was complexed with TPZ and BMS-loaded liposomes via electrostatic interactions to form lipid nanocomposites. This nanoplatform can be triggered by near-infrared irradiation to induce PDT, resulting in a hypoxic tumor environment and activation of the prodrug TPZ to achieve efficient chemotherapy. The in vitro and in vivo studies demonstrated excellent combined PDT, chemotherapy, and immunotherapy effects on the regression of distant tumors and lung metastases, providing a reference method for the preparation of targeted agents for treating breast cancer.
Assuntos
Neoplasias da Mama , Imunoterapia , Lipossomos , Lipossomos/química , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/terapia , Imunoterapia/métodos , Animais , Camundongos , Humanos , Linhagem Celular Tumoral , Fotoquimioterapia/métodos , Verde de Indocianina/química , Verde de Indocianina/uso terapêutico , Verde de Indocianina/análogos & derivados , Camundongos Endogâmicos BALB C , Tirapazamina/química , Tirapazamina/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Fototerapia/métodosRESUMO
Phototherapy is a promising antitumor modality, which consists of photothermal therapy (PTT) and photodynamic therapy (PDT). However, the efficacy of phototherapy is dramatically hampered by local hypoxia in tumors, overexpression of indoleamine 2,3-dioxygenase (IDO) and programmed cell death ligand-1 (PD-L1) on tumor cells. To address these issues, self-assembled multifunctional polymeric micelles (RIMNA) were developed to co-deliver photosensitizer indocyanine green (ICG), oxygenator MnO2, IDO inhibitor NLG919, and toll-like receptor 4 agonist monophosphoryl lipid A (MPLA). It is worth noting that RIMNA polymeric micelles had good stability, uniform morphology, superior biocompatibility, and intensified PTT/PDT effect. What's more, RIMNA-mediated IDO inhibition combined with programmed death receptor-1 (PD-1)/PD-L1 blockade considerably improved immunosuppression and promoted immune activation. RIMNA-based photoimmunotherapy synergized with PD-1 antibody could remarkably inhibit primary tumor proliferation, as well as stimulate the immunity to greatly suppress lung metastasis and distant tumor growth. This study offers an efficient method to reinforce the efficacy of phototherapy and alleviate immunosuppression, thereby bringing clinical benefits to cancer treatment.
Assuntos
Neoplasias do Colo , Imunoterapia , Micelas , Fototerapia , Polímeros , Receptor de Morte Celular Programada 1 , Animais , Neoplasias do Colo/terapia , Neoplasias do Colo/imunologia , Neoplasias do Colo/tratamento farmacológico , Camundongos , Imunoterapia/métodos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Polímeros/química , Linhagem Celular Tumoral , Fototerapia/métodos , Verde de Indocianina/química , Verde de Indocianina/uso terapêutico , Verde de Indocianina/farmacologia , Camundongos Endogâmicos BALB C , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fotoquimioterapia/métodos , Feminino , Humanos , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Lipídeo A/análogos & derivadosRESUMO
Introduction: Photodynamic therapy (PDT) has attracted increasing attention in the clinical treatment of epidermal and luminal tumors. However, the PDT efficacy in practice is severely impeded by tumor hypoxia and the adverse factors associated with hydrophobic photosensitizers (PSs), including low delivery capacity, poor photoactivity and limited ROS diffusion. In this study, Pt nanozymes decorated two-dimensional (2D) porphyrin metal-organic framework (MOF) nanosheets (PMOF@HA) were fabricated and investigated to conquer the obstacles of PDT against hypoxic tumors. Materials and Methods: PMOF@HA was synthesized by the coordination of transition metal iron (Zr4+) and PS (TCPP), in situ generation of Pt nanozyme and surface modification with hyaluronic acid (HA). The abilities of hypoxic relief and ROS generation were evaluated by detecting the changes of O2 and 1O2 concentration. The cellular uptake was investigated using flow cytometry and confocal laser scanning microscopy. The SMMC-7721 cells and the subcutaneous tumor-bearing mice were used to demonstrate the PDT efficacy of PMOF@HA in vitro and in vivo, respectively. Results: Benefiting from the 2D structure and inherent properties of MOF materials, the prepared PMOF@HA could not only serve as nano-PS with high PS loading but also ensure the rational distance between PS molecules to avoid aggregation-induced quenching, enhance the photosensitive activity and promote the rapid diffusion of generated radical oxide species (ROS). Meanwhile, Pt nanozymes with catalase-like activity effectively catalyzed intratumoral overproduced H2O2 into O2 to alleviate tumor hypoxia. Additionally, PMOF@HA, with the help of externally coated HA, significantly improved the stability and increased the cell uptake by CD44 overexpressed tumor cells to strengthen O2 self-supply and PDT efficacy. Conclusion: This study provided a new strategy of integrating 2D porphyrin MOF nanosheets with nanozymes to conquer the obstacles of PDT against hypoxic tumors.
Assuntos
Ácido Hialurônico , Estruturas Metalorgânicas , Fotoquimioterapia , Fármacos Fotossensibilizantes , Porfirinas , Hipóxia Tumoral , Fotoquimioterapia/métodos , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Animais , Camundongos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/administração & dosagem , Linhagem Celular Tumoral , Humanos , Hipóxia Tumoral/efeitos dos fármacos , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Porfirinas/química , Porfirinas/farmacologia , Porfirinas/farmacocinética , Porfirinas/administração & dosagem , Espécies Reativas de Oxigênio/metabolismo , Platina/química , Platina/farmacologia , Nanoestruturas/química , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias/tratamento farmacológico , Sobrevivência Celular/efeitos dos fármacosAssuntos
Colágeno , Reagentes de Ligações Cruzadas , Pressão Intraocular , Ceratocone , Ceratectomia Fotorrefrativa , Ceratocone/cirurgia , Ceratocone/fisiopatologia , Ceratocone/diagnóstico , Humanos , Ceratectomia Fotorrefrativa/métodos , Pressão Intraocular/fisiologia , Colágeno/metabolismo , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Crosslinking CorneanoRESUMO
PURPOSE: This study aimed to identify preoperative factors that predict visual acuity and Kmax 3 years after corneal cross-linking (CXL) in patients with keratoconus (KC), and to develop a prediction model. METHODS: We enrolled 68 patients with KC and followed up on 100 eyes that received CXL for at least 3 years. Preoperative data, including age, UDVA, CDVA, cylinder, SE, and the parameters of tomography including Kmax were collected as predictors. The primary outcomes were changes in CDVA (Delta CDVA) and Kmax (Delta Kmax) postoperatively. Univariate and multivariate linear regression were used to identify the correlation between the primary outcomes and predictors and establish prediction models. RESULTS: Both CDVA and Kmax remained stable from baseline to 3 years after CXL: from 0.25 ± 0.18 to 0.22 ± 0.20 (P = 0.308) and from 58.70 ± 9.52 D to 57.02 ± 8.83 D (P = 0.187), respectively. Multivariate analysis showed that worse preoperative CDVA (ß coefficient - 0.668, P < 0.001) and lower preoperative Kmean (ß coefficient 0.018,P < 0.001) were associated with greater improvement in CDVA after CXL. A smaller preoperative eccentricity (ß coefficient 8.896, P = 0.01) and a higher preoperative Kmean (ß coefficient - 1.264, P < 0.001) predicted a more flattening of postoperative Kmax. The prediction model for CDVA (R2 = 0.43) and Kmax (R2 = 0.37) could accurately estimate treatment outcomes. CONCLUSIONS: CXL is highly effective in halting or preventing further progression of KC. The preoperative factors CDVA and Kmean were able to predict visual acuity changes 3 years after CXL. And preoperative eccentricity and Kmean could predict Kmax changes 3 years after CXL.
Assuntos
Colágeno , Topografia da Córnea , Reagentes de Ligações Cruzadas , Ceratocone , Fotoquimioterapia , Fármacos Fotossensibilizantes , Riboflavina , Raios Ultravioleta , Acuidade Visual , Humanos , Ceratocone/tratamento farmacológico , Ceratocone/diagnóstico , Ceratocone/metabolismo , Reagentes de Ligações Cruzadas/uso terapêutico , Feminino , Masculino , Fármacos Fotossensibilizantes/uso terapêutico , Adulto , Colágeno/metabolismo , Riboflavina/uso terapêutico , Fotoquimioterapia/métodos , Adulto Jovem , Seguimentos , Estudos Retrospectivos , Resultado do Tratamento , Adolescente , Refração Ocular/fisiologia , Córnea/patologia , Córnea/diagnóstico por imagem , Fatores de Tempo , Substância Própria/metabolismo , Substância Própria/efeitos dos fármacos , Crosslinking CorneanoRESUMO
The poor 5-year survival rate for bladder cancers is associated with the lack of efficient diagnostic and treatment techniques. Despite cystoscopy-assisted photomedicine and external radiation being promising modalities to supplement or replace surgery, they remain invasive or fail to provide real-time navigation. Here, we report non-invasive fractionated photodynamic therapy of bladder cancer with full-course real-time near-infrared-II imaging based on engineered X-ray-activated nanotransducers that contain lanthanide-doped nanoscintillators with concurrent emissions in visible and the second near-infrared regions and conjugated photosensitizers. Following intravesical instillation in mice with carcinogen-induced autochthonous bladder tumours, tumour-homing peptide-labelled nanotransducers realize enhanced tumour regression, robust recurrence inhibition, improved survival rates, and restored immune homeostasis under X-ray irradiation with accompanied near-infrared-II imaging. On-demand fractionated photodynamic therapy with customized doses is further achieved based on quantifiable near-infrared-II imaging signal-to-background ratios. Our study presents a promising non-invasive strategy to confront the current bladder cancer dilemma from diagnosis to treatment and prognosis.
Assuntos
Fotoquimioterapia , Fármacos Fotossensibilizantes , Neoplasias da Bexiga Urinária , Animais , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Fotoquimioterapia/métodos , Camundongos , Fármacos Fotossensibilizantes/uso terapêutico , Raios X , Linhagem Celular Tumoral , Feminino , Humanos , Raios InfravermelhosRESUMO
At present, chemotherapy combined with photodynamic therapy is exerting satisfactory therapeutic effects in the treatment of tumors. Chlorin e6 (Ce6) is a photosensitizer with high efficiency and low dark toxicity. At the same time, elemene (ELE) contains high-efficiency and low-toxicity anti-cancer active ingredients, which can effectively penetrate tumor tissue and inhibit its recovery and proliferation. Due to the poor water solubility of these two drugs, we prepared ELE/Ce6 co-loaded liposomes (Lipo-ELE/Ce6) to improve their water solubility, thereby enhancing the anti-tumor effect. The characterization of Lipo-ELE/Ce6 showed that Lipo-ELE/Ce6 had suitable encapsulation efficiency (EE), particle size, polydispersity (PDI), zeta potential, and good photo-controlled release properties. In vitro, Lipo-ELE/Ce6 effectively inhibited the growth of T24 cells and induced apoptosis, and more importantly, in vivo experiments showed that Lipo-ELE/Ce6 had significant anti-tumor effects, which was significantly better than free drugs. The above results suggest that Lipo-ELE/Ce6 can significantly enhance the induction of apoptosis of non-muscle invasive bladder cancer (NMIBC) by light-controlled release and ROS response.
Assuntos
Apoptose , Clorofilídeos , Preparações de Ação Retardada , Lipossomos , Fármacos Fotossensibilizantes , Porfirinas , Espécies Reativas de Oxigênio , Apoptose/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Animais , Humanos , Linhagem Celular Tumoral , Porfirinas/farmacologia , Porfirinas/química , Porfirinas/administração & dosagem , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/química , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Fotoquimioterapia/métodos , Camundongos Nus , Camundongos , Liberação Controlada de Fármacos , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Solubilidade , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/administração & dosagem , Proliferação de Células/efeitos dos fármacos , Neoplasias não Músculo Invasivas da BexigaRESUMO
AIM: The aim of our study was to explore the factors influencing cerebral edema and intracranial pressure in glioblastoma multiforme (GBM) patients who undergo photodynamic therapy (PDT) after resection. APPROACH: This was a retrospective controlled study of GBM patients treated with PDT-assisted resections of varying scope from May 2021 to August 2023. The baseline clinical data, cerebral edema volumes, intracranial pressure values, and imaging data of the GBM patients were collected for statistical analysis. RESULTS: A total of 56 GBM patients were included. Thirty of the patients underwent gross total resection (GTR), and the other 26 patients underwent subtotal resection (STR). We found that the cerebral edema volume and the mean intracranial pressure in patients who underwent GTR were lower than those in patients who underwent STR. Moreover, univariate analysis showed that the scope of tumor resection was an independent factor affecting cerebral edema and intracranial pressure after PDT. CONCLUSIONS: Compared with STR, PDT combined with GTR significantly reduced postoperative brain edema volume and intracranial pressure in GBM patients.
Assuntos
Edema Encefálico , Neoplasias Encefálicas , Glioblastoma , Pressão Intracraniana , Fotoquimioterapia , Humanos , Estudos Retrospectivos , Edema Encefálico/etiologia , Edema Encefálico/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Masculino , Feminino , Fotoquimioterapia/métodos , Pessoa de Meia-Idade , Adulto , Pressão Intracraniana/efeitos dos fármacos , Glioblastoma/cirurgia , Glioblastoma/tratamento farmacológico , Complicações Pós-Operatórias , Idoso , Resultado do Tratamento , Fármacos Fotossensibilizantes/uso terapêutico , Procedimentos NeurocirúrgicosRESUMO
Darier disease and Hailey-Hailey disease are rare autosomal dominant genodermatoses that negatively impact patient quality of life. In addition, they pose challenges to dermatologists who manage these diseases. There is currently no treatment that reliably induces remission for either disease, leaving patients dependent on symptom management. Oral and topical retinoids are the most commonly used therapies but have numerous side effects that often lead to discontinuation or inability to tolerate long-term treatment (Burge and Wilkinson in J Am Acad Dermatol 27:40-50, 1992). Due to the rarity of these diseases, there are no clinical trials investigating treatment options for the persistent flares patients experience. In light of this, dermatologists have tried various methods used in the management of other inflammatory disorders including photodynamic therapy (PDT). A systematic review was conducted to investigate this treatment option which yielded a total of 12 studies that had reported the use of photodynamic therapy (PDT) as a treatment option for Darier or Hailey-Hailey disease. Though results showed that PDT can induce disease remission for up to several months or years, there are many unanswered questions that need to be addressed before adopting PDT as a leading treatment option for those genodermatoses. In particular, cost, tolerability, and efficacy and safety in patients who are skin of color need to be further studied. Lastly, recommendations on treatment duration, number of sessions, photosensitizing agents, lasers, and continuation or discontinuation of topical and systemic medications need to be appraised before formal recommendations can be made.
Assuntos
Doença de Darier , Pênfigo Familiar Benigno , Fotoquimioterapia , Fármacos Fotossensibilizantes , Humanos , Doença de Darier/tratamento farmacológico , Doença de Darier/psicologia , Pênfigo Familiar Benigno/tratamento farmacológico , Pênfigo Familiar Benigno/psicologia , Fotoquimioterapia/métodos , Fotoquimioterapia/efeitos adversos , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/efeitos adversos , Qualidade de Vida , Resultado do TratamentoRESUMO
The combination of chemotherapy and photodynamic therapy (PDT), enabled by core-shell nano-platforms, is a promising method to improve cancer therapy by overcoming hypoxia and boosting drug penetration in breast tumor. Core-shell magnetic (iron oxide: Fe3O4)@platinum-metal organic framework/epirubicin (abbreviated as M@Pt-MOF/EPI) nano-platform is considered an effective cancer therapeutic agent. Relatively small particle size, round shape, and specific response to pH, are the key features of these nanomaterials to be used as promising therapeutic agents. Chemotherapy and photodynamic therapy, when applied in addition to the anticancer effects of nanomaterials, further enhance the therapeutic efficacy. The extensive use, utilization, and efficacy of Core-Shell Magnetic@Platinium-Metal Organic Framework/epirubicin Nano-Platforms for chemo-photodynamic combination therapy in the treatment of several cancers, including triple-negative breast cancer, are examined in this in-depth investigation.