RESUMEN

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.

Asunto(s)

Fluorocarburos , Nanopartículas , Fotoquimioterapia , Fármacos Fotosensibilizantes , Especies Reactivas de Oxígeno , Microambiente Tumoral , Nanopartículas/química , Microambiente Tumoral/efectos de los fármacos , Animales , Fotoquimioterapia/métodos , Especies Reactivas de Oxígeno/metabolismo , Fluorocarburos/química , Fluorocarburos/farmacología , Línea Celular Tumoral , Fármacos Fotosensibilizantes/uso terapéutico , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Humanos , Ratones , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Ratones Endogámicos BALB C , Terapia Fototérmica/métodos , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Fototerapia/métodos , Femenino

RESUMEN

Sonodynamic therapy (SDT) relies heavily on the presence of oxygen to induce cell death. Its effectiveness is thus diminished in the hypoxic regions of tumor tissue. To address this issue, the exploration of ultrasound-based synergistic treatment modalities has become a significant research focus. Here, we report an ultrasonic cavitation effect enhanced sonodynamic and 1208 nm photo-induced cancer treatment strategy based on thermoelectric/piezoelectric oxygen-defect bismuth oxychloride nanosheets (BNs) to realize the high-performance eradication of tumors. Upon ultrasonic irradiation, the local high temperature and high pressure generated by the ultrasonic cavitation effect combined with the thermoelectric and piezoelectric effects of BNs create a built-in electric field. This facilitates the separation of carriers, increasing their mobility and extending their lifetimes, thereby greatly improving the effectiveness of SDT and NIR-Ⅱ phototherapy on hypoxia. The Tween-20 modified BNs (TBNs) demonstrate ∼88.6 % elimination rate against deep-seated tumor cells under hypoxic conditions. In vivo experiments confirm the excellent antitumor efficacy of TBNs, achieving complete tumor elimination within 10 days with no recurrences. Furthermore, due to the high X-ray attenuation of Bi and excellent NIR-Ⅱ absorption, TBNs enable precise cancer diagnosis through photoacoustic (PA) imaging and computed tomography (CT).

Asunto(s)

Bismuto , Neoplasias de la Mama , Oxígeno , Terapia por Ultrasonido , Bismuto/química , Femenino , Animales , Neoplasias de la Mama/terapia , Terapia por Ultrasonido/métodos , Oxígeno/química , Ratones , Ratones Endogámicos BALB C , Humanos , Línea Celular Tumoral , Rayos Infrarrojos , Nanoestructuras/química , Fototerapia/métodos

RESUMEN

Background: Effective innate immunity activation could dramatically improve the anti-tumor efficacy and increase the beneficiary population of immunotherapy. However, the anti-tumor effect of unimodal immunotherapy is still not satisfactory. Methods: Herein, a novel relay-type innate immunity activation strategy based on photo-immunotherapy mediated by a water-soluble aggregation-induced emission luminogen, PEG420-TQ, with the assistant of toll-like receptor 7 (TLR-7) agonist, imiquimod (R837), was developed and constructed. Results: The strategy could promote tumor cells to undergo immunogenic cell death (ICD) induced by the well-designed PEG420-TQ@R837 (PTQ@R) nanoplatform under light irradiation, which in turn enhanced the infiltration of immune cells and the activation of innate immune cells to achieve the first innate immunity activation. The second innate immunity activation was subsequently achieved by drug delivery of R837 via apoptotic bodies (ApoBDs), further enhancing the anti-tumor activity of infiltrated immune cells. Conclusion: The strategy ultimately demonstrated robust innate immunity activation and achieved excellent performance against tumor growth and metastasis. The construction of the relay-type innate immunity activation strategy could provide a new idea for the application of immunotherapy in clinical trials.

Asunto(s)

Imiquimod , Inmunidad Innata , Inmunoterapia , Inmunidad Innata/efectos de los fármacos , Animales , Inmunoterapia/métodos , Ratones , Imiquimod/uso terapéutico , Imiquimod/farmacología , Línea Celular Tumoral , Humanos , Neoplasias/inmunología , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Agua/química , Receptor Toll-Like 7/agonistas , Femenino , Fototerapia/métodos , Nanopartículas/química , Ratones Endogámicos BALB C , Muerte Celular Inmunogénica/efectos de los fármacos , Rayos Infrarrojos

RESUMEN

Breast cancer is a malignant tumor that poses a significant threat to women's health and single therapy fails to play a good oncological therapeutic effect. Synergistic treatment with multiple strategies may make up for the deficiencies and has gained widespread attention. In this study, sulfhydryl-modified hyaluronic acid (HA-SH) was covalently crosslinked with polydopamine (PDA) via a Michael addition reaction to develop an injectable hydrogel, in which PDA can be used not only as a matrix but also as a photothermal agent. After HSA and paclitaxel were spontaneously organized into nanoparticles via hydrophobic interaction, hyaluronic acid with low molecular weight was covalently linked to HSA, thus conferring effectively delivery. This photothermal injectable hydrogel incorporates PTX@HSA-HA nanoparticles, thereby initiating a thermochemotherapeutic response to target malignancy. Our results demonstrated that this injectable hydrogel possesses consistent drug delivery capability in a murine breast cancer model, collaborating with photothermal therapy to effectively suppress tumor growth, represented by low expression of Ki-67 and increasing apoptosis. Photothermal therapy (PTT) can effectively stimulate immune response by increasing IL-6 and TNF-α. Notably, the treatment did not elicit any indications of toxicity. This injectable hydrogel holds significant promise as a multifaceted therapeutic agent that integrates photothermal and chemotherapeutic modalities.

Asunto(s)

Neoplasias de la Mama , Ácido Hialurónico , Hidrogeles , Paclitaxel , Terapia Fototérmica , Animales , Ácido Hialurónico/química , Hidrogeles/química , Hidrogeles/farmacología , Femenino , Neoplasias de la Mama/terapia , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Ratones , Terapia Fototérmica/métodos , Paclitaxel/farmacología , Paclitaxel/química , Paclitaxel/administración & dosificación , Humanos , Indoles/química , Indoles/farmacología , Ratones Endogámicos BALB C , Polímeros/química , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Nanopartículas/química , Portadores de Fármacos/química , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Fototerapia/métodos

RESUMEN

OBJECTIVE: Vulvovaginal Candidiasis (VVC) is a prevalent genital infection in women of reproductive age and requires effective non-drug therapies. Therefore, this study aimed to investigate the effect of blue light emitting diode (LED) therapy as an alternative treatment for recurrent VVC due to its proven antimicrobial properties. The safety and non-invasiveness of LED therapy make it a promising option for sensitive tissue applications. MATERIALS AND METHODS: This randomized controlled trial recruited 60 women with culture-confirmed VVC. Participants were randomly allocated to two groups. Group A (control group) received standard antifungal treatment with Gynoconazol 0.8% vaginal cream for three consecutive nights (n = 30). Group B (study group) received the same antifungal treatment plus two 60-min sessions of blue LED therapy directed at the vagina and vulva, with the sessions separated by two days (n = 30). Candida count (via CHROMagar™ Candida) and vaginal pH (via AD110-AD111 m) were assessed at baseline and one week after initiating treatment. RESULTS: Post-treatment, group (B) demonstrated a significantly greater reduction in Candida count compared to group (A) (mean difference (MD) 8.267; 95% Confidence Interval (CI) 6.723-9.811; p = 0.0001). However, there was no statistically significant difference in vaginal pH between the groups (MD -0.03; 95% CI -0.244-0.178; p = 0.749). CONCLUSION: Blue LED therapy effectively reduces Candida count in women with recurrent VVC without adversely affecting the vaginal pH, highlighting its safety and efficacy as a treatment modality.

Asunto(s)

Candidiasis Vulvovaginal , Humanos , Femenino , Candidiasis Vulvovaginal/terapia , Candidiasis Vulvovaginal/tratamiento farmacológico , Adulto , Fototerapia/métodos , Antifúngicos/uso terapéutico , Recurrencia , Adulto Joven , Método Simple Ciego , Resultado del Tratamiento , Luz Azul

RESUMEN

Rationale: Optogenetically engineered facultative anaerobic bacteria exhibit a favorable tendency to colonize at solid tumor sites and spatiotemporally-programmable therapeutics release abilities, attracting extensive attention in precision tumor therapy. However, their therapeutic efficacy is moderate. Conventional photothermal agents with high tumor ablation capabilities exhibit low tumor targeting efficiency, resulting in significant off-target side effects. The combination of optogenetics and photothermal therapy may offer both tumor-targeting and excellent tumor-elimination capabilities, which unfortunately has rarely been investigated. Herein, we construct a bacteria-based cascade near-infrared optogentical-photothermal system (EcNαHL-UCNPs) for enhanced tumor therapy. Methods: EcNαHL-UCNPs consists of an optogenetically engineered Escherichia coli Nissle 1917 (EcN) conjugated with lanthanide-doped upconversion nanoparticles (UCNPs), which are capable of locally secreting α-hemolysin (αHL), a pore-forming protein, in responsive to NIR irradiation. Anti-tumor effects of EcNαHL-UCNPs were determined in both H22 and 4T1 tumors. Results: The αHL not only eliminates tumor cells, but more importantly disrupts endothelium to form thrombosis as an in situ photothermal agent in tumors. The in situ formed thrombosis significantly potentiates the photothermic ablation of H22 tumors upon subsequent NIR light irradiation. Besides, αHL secreted by EcNαHL-UCNPs under NIR light irradiation not only inhibits 4T1 tumor growth, but also suppresses metastasis of 4T1 tumor via inducing the immune response. Conclusion: Our studies highlight bacteria-based cascade optogenetical-photothermal system for precise and effective tumor therapy.

Asunto(s)

Escherichia coli , Nanopartículas , Optogenética , Terapia Fototérmica , Animales , Ratones , Terapia Fototérmica/métodos , Escherichia coli/genética , Línea Celular Tumoral , Nanopartículas/química , Optogenética/métodos , Ratones Endogámicos BALB C , Rayos Infrarrojos , Femenino , Neoplasias/terapia , Humanos , Fototerapia/métodos

RESUMEN

Hepatocellular carcinoma (HCC) is a serious health issue due to its low early diagnosis rate, resistance to chemotherapy, and poor five-year survival rate. Therefore, it is crucial to explore novel diagnostic and therapeutic approaches tailored to the characteristics of HCC. Aggregation-induced emission (AIE) is a phenomenon where the luminescence of certain molecules, typically non-luminescent or weakly luminescent in solution, is significantly enhanced upon aggregation. AIE has been extensively applied in bioimaging, biosensors, and therapy. Fluorophore materials based on AIE (AIEgens) have a wide range of application scenarios and potential for clinical translation. This review focuses on recent advances in AIE-based strategies for diagnosing and treating HCC. First, the specific functional mechanism of AIE is described. Next, we summarize recent progress in the application of AIE for multimodal imaging, biosensor detection, and phototherapy. Finally, prospects and challenges for the AIE-based application in the diagnosis and therapy of HCC are discussed.

Asunto(s)

Técnicas Biosensibles , Carcinoma Hepatocelular , Neoplasias Hepáticas , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/terapia , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/diagnóstico por imagen , Humanos , Técnicas Biosensibles/métodos , Colorantes Fluorescentes/química , Animales , Fototerapia , Imagen Óptica/métodos , Imagen Multimodal/métodos

RESUMEN

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.

Asunto(s)

Neoplasias del Colon , Inmunoterapia , Micelas , Fototerapia , Polímeros , Receptor de Muerte Celular Programada 1 , Animales , Neoplasias del Colon/terapia , Neoplasias del Colon/inmunología , Neoplasias del Colon/tratamiento farmacológico , Ratones , Inmunoterapia/métodos , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Polímeros/química , Línea Celular Tumoral , Fototerapia/métodos , Verde de Indocianina/química , Verde de Indocianina/uso terapéutico , Verde de Indocianina/farmacología , Ratones Endogámicos BALB C , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Fotoquimioterapia/métodos , Femenino , Humanos , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/metabolismo , Lípido A/análogos & derivados

RESUMEN

For many of the complementary and alternative (CAM) medicine methods, it is biologically plausible to expect that they could provide additional benefits in the treatment of major depressive disorder (e.g., enhanced initial response, augmentation, and tolerability) when combined with conventional treatments. Although most likely not comprehensively, herein we critically review current explicit clinical data pertaining to the most extensively evaluated CAMs in this setting: physical activity/exercise, mind and body methods, acupuncture, light therapy, diet, probiotics, various nutrients, and herbal preparations. While the absolute amount of data is enormous, the number of reliable primary studies (randomized controlled trials) and, particularly, meaningful meta-analyses of such studies are very limited. Consequently, the certainty of evidence about benefit or no benefit is very low for each of the addressed CAMs.

Asunto(s)

Terapias Complementarias , Trastorno Depresivo Mayor , Humanos , Trastorno Depresivo Mayor/terapia , Terapias Complementarias/métodos , Terapia Combinada , Probióticos/uso terapéutico , Terapia por Acupuntura/métodos , Fototerapia/métodos , Resultado del Tratamiento , Terapias Mente-Cuerpo/métodos , Ejercicio Físico

RESUMEN

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.

Asunto(s)

Neoplasias de la Mama , Inmunoterapia , Liposomas , Liposomas/química , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/terapia , Inmunoterapia/métodos , Animales , Ratones , Humanos , Línea Celular Tumoral , Fotoquimioterapia/métodos , Verde de Indocianina/química , Verde de Indocianina/uso terapéutico , Verde de Indocianina/análogos & derivados , Ratones Endogámicos BALB C , Tirapazamina/química , Tirapazamina/farmacología , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Fototerapia/métodos

RESUMEN

Purpose: Our study seeks to develop dual-modal organic-nanoagents for cancer therapy and real-time fluorescence imaging, followed by their pre-clinical evaluation on a murine model. Integrating NIR molecular imaging with nanotechnology, our aim is to improve outcomes for early-stage cutaneous melanoma by offering more effective and less invasive methods. This approach has the potential to enhance both photothermal therapy (PTT) and Sentinel Lymph Node Biopsy (SLNB) procedures for melanoma patients. Methods: NIR-797-isothiocyanate was encapsulated in poly(D,L-lactide-co-glycolide) acid (PLGA) nanoparticles (NPs) using a two-step protocol, followed by thorough characterization, including assessing loading efficiency, fluorescence stability, and photothermal conversion. Biocompatibility and cellular uptake were tested in vitro on melanoma cells, while PTT assay, with real-time thermal monitoring, was performed in vivo on tumor-bearing mice under irradiation with an 808 nm laser. Finally, ex vivo fluorescence microscopy, histopathological assay, and TEM imaging were performed. Results: Our PLGA NPs, with a diameter of 270 nm, negative charge, and 60% NIR-797 loading efficiency, demonstrated excellent stability and fluorescence properties, as well as efficient light-to-heat conversion. In vitro studies confirmed their biocompatibility and cellular internalization. In vivo experiments demonstrated their efficacy as photothermal agents, inducing mild hyperthermia with temperatures reaching up to 43.8 °C. Ex vivo microscopy of tumor tissue confirmed persistent NIR fluorescence and uniform distribution of the NPs. Histopathological and TEM assays revealed early apoptosis, immune cell response, ultrastructural damage, and intracellular material debris resulting from combined NP treatment and irradiation. Additionally, TEM analyses of irradiated zone margins showed attenuated cellular damage, highlighting the precision and effectiveness of our targeted treatment approach. Conclusion: Specifically tailored for dual-modal NIR functionality, our NPs offer a novel approach in cancer PTT and real-time fluorescence monitoring, signaling a promising avenue toward clinical translation.

Asunto(s)

Hipertermia Inducida , Nanopartículas , Imagen Óptica , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Animales , Nanopartículas/química , Ratones , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Línea Celular Tumoral , Hipertermia Inducida/métodos , Humanos , Terapia Fototérmica/métodos , Neoplasias Cutáneas/terapia , Neoplasias Cutáneas/diagnóstico por imagen , Neoplasias Cutáneas/patología , Melanoma/terapia , Melanoma/diagnóstico por imagen , Fototerapia/métodos

RESUMEN

Chemodynamic therapy is an appealing modality in cancer treatment. However, its therapeutic effectiveness is impeded by insufficient catalytic efficiency and overexpression of glutathione (GSH) at the tumor site. In this study, a poly(o-phenylenediamine) (PoPD)@copper sulfide (CuS) nanoplatform was developed as dual-level reactive oxygen species (ROS) amplifier for enhanced photothermal-chemodynamic therapy. The PoPD@CuS nanoplatform exhibited photothermal performance, chemodynamic performance, and GSH-depleting capability. Alongside its improved photothermal conversion efficiency with tumor pH-responsiveness, the photothermal behavior of PoPD@CuS could elevate chemodynamic activity by regulating the temperature spatiotemporally, leading to increased ROS production. Moreover, GSH depletion of PoPD@CuS could suppress ROS scavenging, further enhancing oxidative stress in the tumor region. Consequently, functioning as a dual-level ROS amplifier, PoPD@CuS showcased remarkable effectiveness in photothermal-chemodynamic combination therapy.

Asunto(s)

Cobre , Especies Reactivas de Oxígeno , Especies Reactivas de Oxígeno/metabolismo , Cobre/química , Cobre/farmacología , Humanos , Animales , Fenilendiaminas/química , Fenilendiaminas/farmacología , Glutatión/metabolismo , Glutatión/química , Ratones , Terapia Fototérmica , Fototerapia/métodos , Línea Celular Tumoral , Antineoplásicos/química , Antineoplásicos/farmacología

RESUMEN

Near-infrared II (NIR-II) imaging and photothermal therapy hold tremendous potential in precision diagnosis and treatment within biological organisms. However, a significant challenge is the shortage of NIR-II fluorescent probes with both high photothermal conversion coefficient (PCE) and fluorescence quantum yield (ΦF). Herein, we address this issue by integrating a large conjugated electron-withdrawing core, multiple rotors, and multiple alkyl chains into a molecule to successfully generate a NIR-II agent 4THTPB with excellent PCE (87.6%) and high ΦF (3.2%). 4THTPB shows a maximum emission peak at 1058 nm, and the emission tail could extend to as long as 1700 nm. These characteristics make its nanoparticles (NPs) perform well in NIR-II high-resolution angiography, thereby allowing for precise diagnosis of thrombus through NIR-II imaging and enabling efficient photothermal thrombolysis. This work not only furnishes a NIR-II agent with excellent overall performance but also provides valuable guidance for the design of high-performance NIR-II agents.

Asunto(s)

Colorantes Fluorescentes , Rayos Infrarrojos , Colorantes Fluorescentes/química , Humanos , Nanopartículas/química , Terapia Fototérmica , Animales , Imagen Óptica , Ratones , Trombosis/diagnóstico por imagen , Terapia Trombolítica , Fototerapia

RESUMEN

ConspectusDue to the advantages of spatiotemporal selectivity and inherent noninvasiveness, cancer phototherapy, which includes both photodynamic therapy (PDT) and photothermal therapy (PTT), has garnered significant attention in recent years as a promising cancer treatment. Despite the commendable progress in this field, persistent challenges remain. In PDT, limitations in dyes manifest as low intersystem crossing (ISC) efficiency and oxygen-dependent photoactivity, resulting in unsatisfactory performance, particularly under hypoxic conditions. Similarly, PTT encounters consistent insufficiencies in the photothermal conversion efficiency (PCE) of dyes. Additionally, the suboptimal phototherapeutic efficacy often exhibits a limited immune response. These factors collectively impose significant constraints on phototherapy in oncological applications, leading to limited tumor inhibition, tumor recurrence, and even metastasis.Unlike strategies that rely on external assistance with complicated systems, manipulating excited-state deactivation pathways in biocompatible dyes offers a universal way to systematically address these challenges. Our group has devoted considerable effort to achieving this goal. In this Account, we present and discuss our journey in optimizing excited-state energy-release pathways through regulating molecular charge transfer based on cyanine dyes, which are renowned for their exceptional photophysical properties and harmonious biocompatibility. The investigation begins with the introduction of amino groups in the meso position of a heptamethine cyanine dye, where the intramolecular charge transfer (ICT) effect causes a significant enlargement of the Stokes shift. Subsequently, ICT induced by introducing functional electron-deficient groups in cyanines is found to decrease the overlap of electron distribution or narrow the energy gaps of molecular frontier orbitals. Such modifications result in a reduction of the energy gaps between singlet and triplet states or an improvement in internal conversion, ultimately promoting phototherapy efficacy in both primary and distant tumors. Furthermore, with the intensification of the charge transfer effect aided by light, photoinduced intramolecular electron transfer occurs in some cyanines, leading to complete charge separation in the excited state. This process enhances the transition to the ground or triplet states, improving tumor phototherapy and inhibiting metastasis by increasing the PCE or the yield of reactive oxygen species, respectively. Shifting focus from intramolecular to intermolecular interactions, we successfully constructed and explored cyanines based on intermolecular charge transfer. These dyes, with excited-state dynamics mimicking natural photosynthesis, generate radicals and facilitate oxygen-independent hypoxic tumor PDT. Finally, we outlined the existing challenges and future directions for optimizing phototherapeutic efficacy by regulating molecular charge transfer. This Account provides molecular-level insights into improving phototherapeutic performance, offering valuable perspectives, and inspiring the development of functional dyes in other application fields.

Asunto(s)

Carbocianinas , Neoplasias , Carbocianinas/química , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Colorantes/química , Colorantes/farmacología , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/uso terapéutico , Fármacos Fotosensibilizantes/farmacología , Fotoquimioterapia , Animales , Fototerapia/métodos

RESUMEN

Vitamin D plays a role in inflammatory skin disease, but the exact mechanisms and the clinical significance remain unclear. According to the free hormone hypothesis, it is the free concentration of 25-hydroxy vitamin D (25(OH)D) that is biologically active. Vitamin D-binding protein (DBP) acts as the major transporter of vitamin D in the circulation, and DBP concentration defines the free 25(OH)D levels. DBP levels are elevated in various inflammatory conditions, including psoriasis. Narrowband-ultraviolet B (NB-UVB) is the most widely used phototherapy and is an established first-line treatment for psoriasis and atopic dermatitis (AD), often used before proceeding to systemic treatment. The aim of this study was to investigate the influence of NB-UVB phototherapy on DBP and high-sensitivity C-reactive protein (hsCRP) levels, as markers of systemic inflammation, in inflammatory skin disease. Thirty adults (psoriasis (n = 20) and AD (n = 10)) were treated with NB-UVB. Serum DBP, hsCRP, total and free 25(OH)D, and 1,25-dihydroxy vitamin D (1,25(OH)2D) were measured before and after NB-UVB. Disease severity was assessed with Psoriasis Area and Severity Index (PASI), SCORing Atopic Dermatitis (SCORAD), and Visual Analogue Scale (VAS). DBP decreased in psoriasis patients and varied with no clear trend in AD patients. HsCRP decreased in both groups, but this did not reach statistical significance. PASI, SCORAD, and VAS improved, and vitamin D levels increased after NB-UVB. Sub-analysis indicated a better response to NB-UVB for patients with vitamin D deficiency and insufficiency compared to vitamin D-sufficient patients. The decrease in DBP after NB-UVB in psoriasis patients suggests a potential systemic anti-inflammatory effect of phototherapy. Measurement of vitamin D levels may potentially serve as a tool to identify patients who would derive the greatest benefit from NB-UVB phototherapy.

Asunto(s)

Proteína C-Reactiva , Dermatitis Atópica , Psoriasis , Terapia Ultravioleta , Proteína de Unión a Vitamina D , Vitamina D , Humanos , Proteína de Unión a Vitamina D/sangre , Femenino , Masculino , Psoriasis/sangre , Psoriasis/terapia , Psoriasis/radioterapia , Adulto , Persona de Mediana Edad , Proteína C-Reactiva/metabolismo , Proteína C-Reactiva/análisis , Dermatitis Atópica/sangre , Dermatitis Atópica/terapia , Vitamina D/sangre , Vitamina D/análogos & derivados , Terapia Ultravioleta/métodos , Inflamación/sangre , Biomarcadores/sangre , Fototerapia/métodos , Anciano , Índice de Severidad de la Enfermedad

RESUMEN

PURPOSE: The management of pressure ulcers (PUs) poses challenges due to their chronic nature and the lack of established conservative treatment methods. In this clinical trial, our objective was to examine the validity and safety of using a light-emitting diode device contained four wavelengths in the treatment of grade 2 sacral PUs. METHOD: A total of 38 patients were randomly assigned to two groups: sham device (Sham) and experimental device (LED) group. The treatment sessions were conducted over a period of four weeks, with a frequency of three times per week. The study was conducted in a double-blinded manner. The study assessed the primary validity by measuring wound size and re-epithelialization after 0 and 4 weeks. Secondary evaluations included epidermal regeneration, collagen density, and immunological markers. Safety was evaluated by monitoring adverse reactions throughout the trial. RESULT: The presence of eschar was found to have a significant impact on wound healing. Sham consisted of 15 wounds without eschar, while LED had nine. After treatment in without eschar situation, the post-treatment size of wounds in Sham was 13.80 ± 20.29%, while it was 3.52 ± 6.68% in LED. However, there was no significant difference (p = 0.070). And analysis of epidermal thickness showed a significant increase in LED (495.62 ± 327.09 µm) compared to Sham (195.36 ± 263.04 µm) (p < 0.0001). CONCLUSION: While LED treatment had a potential for wound reduction in PUs without eschar, we could not uncover evidence to support the efficacy of LED treatment in grade 2 PUs.

Asunto(s)

Úlcera por Presión , Cicatrización de Heridas , Humanos , Úlcera por Presión/terapia , Femenino , Masculino , Método Doble Ciego , Persona de Mediana Edad , Anciano , Fototerapia/métodos , Fototerapia/instrumentación , Fototerapia/efectos adversos , Adulto , Resultado del Tratamiento , Repitelización

RESUMEN

An innovative organic small molecule with a D-A structure was synthesized by connecting triphenylamine to BODIPY via a thiophene bridge. Triphenylamine and thiophene units ingeniously modulate the balance between steric hindrance and π-π interactions around the flat aza-BODIPY core. The molecule exhibits near-infrared fluorescence absorption and emits at roughly 1100 nm, featuring a significant Stokes shift. Both the molecule and its nanoparticles demonstrate high stability and achieve a remarkable 35 % photothermal conversion efficiency when conjugated with the P(OEGMA)20-P(Asp)14 copolymer. In vitro assessments show low dark toxicity and outstanding biocompatibility. Moreover, in vivo studies and photothermal therapy in mice indicate substantial tumor shrinkage and reduced recurrence, confirming its potential in cancer treatment. These results highlight the promise of this organic molecule and its nanoparticles for NIR-II imaging-guided photothermal therapy, introducing a novel approach to phototheranostic applications for cancer management.

Asunto(s)

Compuestos de Boro , Colorantes Fluorescentes , Rayos Infrarrojos , Nanopartículas , Péptidos , Nanopartículas/química , Compuestos de Boro/química , Animales , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Ratones , Humanos , Péptidos/química , Nanomedicina Teranóstica/métodos , Terapia Fototérmica , Ratones Endogámicos BALB C , Fototerapia

RESUMEN

The importance of copper homeostasis in mitochondria and copper-triggered modality of mitochondrial cell death have been confirmed. However, the existing copper-based nanoplatforms are focused on synergistic therapies while the intracellular therapeutic targets are relatively scattered. Effective integration of all targets within mitochondria to generate power coalescence remains a challenge. Herein, we developed a novel copper-based delivery system to trigger power coalescence and death vortex within tumor cell mitochondria. Specifically, a mitochondrial targeting "copper missile" loaded with curcumin (termed as Cur@CuS-TPP-HA, CCTH) was designed for cuproptosis/phototherapy/chemotherapy synergistic anti-tumor therapy. Once the CCTH NPs are shuttled to the mitochondria, near-infrared (NIR) irradiation initiates the release of copper ions and curcumin for in situ drug accumulation in cancer cell mitochondria. An excess of copper ions and curcumin can activate cuproptosis and mitochondrial apoptosis pathways, respectively. When combined, they can cause an increase in reactive oxygen species (ROS), damage to mitochondrial DNA (mt-DNA), and a decrease in energy supply, thereby leading to a "vicious circle" of mitochondrial damage that further enhances the tumor-killing efficacy. As a consequence, this "copper missile" exhibits advanced anti-tumor effects as verified through in vitro assessments and in vivo evaluations using the 4T1 breast tumor model, providing a promising approach for cuproptosis-based synergistic anti-tumor therapy.

Asunto(s)

Apoptosis , Cobre , Curcumina , Mitocondrias , Especies Reactivas de Oxígeno , Cobre/química , Cobre/farmacología , Curcumina/química , Curcumina/farmacología , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Animales , Humanos , Ratones , Especies Reactivas de Oxígeno/metabolismo , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Femenino , Fototerapia , Antineoplásicos/farmacología , Antineoplásicos/química , Ratones Endogámicos BALB C

RESUMEN

The aim of this study was to investigate the overall effects of phototherapy on biopterin (BH4), neopterin (BH2), tryptophan (Trp), and behavioral neuroinflammatory reaction in patients with post-stroke depression. There involved a total of 100 hospitalized patients with post-stroke depression at our hospital from February 2021 to December 2022. The participants enrolled were randomly assigned to either the control group or the experimental group. The control group received routine treatment, including medication and psychological support, while the experimental group received 30 min of phototherapy daily for 8 weeks. All participantsvoluntarily participated in the study and provided informed consent. Baseline characteristics of the patients were statistically analyzed. The severity of depressive symptoms was evaluated using the hamilton depression scale (HAMD) and the beck depression inventory (BDI). Levels of amino acid neurotransmitters, including gamma-aminobutyric acid (GABA), aspartic acid (Asp), and glutamic acid (Glu), were measured using radioimmunoassay. Plasma levels of neuroinflammatory factors, such as TNF-α, IL-6, and IL-1ß were, determined using ELISA. Plasma levels of BH4, BH2, and Trp were detected by HPLC. Levels of SOD, GPx, CAT, and MDA in plasma were measured using corresponding kits and colorimetry. Quality of life was assessed using the SF-36 scale. There were no differences in baseline characteristic between the two groups (P > 0.05). The HAMD and BDI scores in the experimental group were lower than those in the control group (P < 0.05), indicating phototherapy could reduce the severity of post-stroke depression. The levels of GABA, Glu, and Asp in both groups significantly increased after treatment compared to their respective levels before treatment (P < 0.01).The levels of GABA in the experimental group were higher than those in the control group (P < 0.01),while the levels of Glu, and Asp were lower than those in the control group (P < 0.01). The plasma levels of TNF-α, IL-6, and IL-1ß in the experimental group were evidently lower than those in the control group (P < 0.05). Moreover, the levels of BH4 and Trp in experimental group were significantly higher than those in the control group (P < 0.05), while the levelsof BH2 in the experimental group were significantly lower than the control group (P < 0.05). Additionally, the levels of SOD, GPx, and CAT in the experimental group were evidently higher than those in the control group (P < 0.05), whereas the levels of MDA in the experimental group were significantly lower than control group (P < 0.05). The experimental group showed higher scores in physical function, mental health, social function, and overall health compared to the control group (P < 0.05). Phototherapy exerted a profound impact on the metabolism of BH4, BH2, and Trp, as well as on behavioral neuroinflammatory reactions and the quality of life in patients suffering from post-stroke depression. Through its ability to optimize the secretion and synthesis of neurotransmitters, phototherapy effectively regulated neuroinflammatory reactions, improved biochemical parameters, enhancedantioxidant capacity, and alleviated depressive symptoms. As a result, phototherapy was considered a valuable adjuvant therapeutic approach for patients with post-stroke depression.

Asunto(s)

Biopterinas , Depresión , Neopterin , Fototerapia , Accidente Cerebrovascular , Triptófano , Humanos , Neopterin/sangre , Triptófano/sangre , Triptófano/metabolismo , Femenino , Masculino , Persona de Mediana Edad , Depresión/terapia , Depresión/etiología , Depresión/sangre , Anciano , Fototerapia/métodos , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/psicología , Biopterinas/análogos & derivados , Enfermedades Neuroinflamatorias/terapia , Enfermedades Neuroinflamatorias/etiología

RESUMEN

Phototherapy has demonstrated substantial development because in the second near-infrared (NIR-II) window it has a larger tissue penetration and fewer adverse consequences. In this work, a particular kind of NIR-II responsive Fe-doped carbon nanoparticles (FDCNs) is synthesized using a one-pot hydrothermal method for combined photothermal and chemodynamic therapy. The mesoporous nanostructure of FDCN, which has a size distribution that exceeds 225 nm, allows for effective acidification. The iron ions released from these nanoparticles can catalyze the decomposition of hydrogen peroxide (H2O2) into hydroxyl radical (•OH) for chemodynamic therapy (CDT). In addition to their CDT utility, FDCN can effectively adsorb and transform 1064 nm light into local heat, achieving a photothermal conversion efficacy (PCE) of 36.3%. This dual functionality not only allows for the direct eradication of cancer cells through photothermal therapy (PTT) but also enhances the chemodynamic reaction, creating a synergistic effect that amplifies the therapeutic outcome. The FDCN has demonstrated remarkable anticancer activity in both cellular and animal tests without incurring major systemic toxicity. This suggests that the compound has great promise for use in clinical cancer therapy.

Asunto(s)

Carbono , Hierro , Nanopartículas , Carbono/química , Humanos , Animales , Hierro/química , Nanopartículas/química , Ratones , Rayos Infrarrojos , Antineoplásicos/química , Antineoplásicos/farmacología , Terapia Fototérmica , Peróxido de Hidrógeno/química , Peróxido de Hidrógeno/farmacología , Neoplasias/tratamiento farmacológico , Neoplasias/terapia , Neoplasias/patología , Fototerapia , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Ratones Endogámicos BALB C