RESUMEN
Black phosphorus (BP) nanosheet is easily oxidized by oxygen and water under ambient environment, thus, reliable BP passivation techniques for biomedical applications is urgently needed. A simple and applicable passivation strategy for biomedical applications was established by encapsulating BP nanosheet into zeolitic imidazole framework-8 (ZIF-8). The resulted BP nanosheet in ZIF-8 (BP@ZIF-8) shows not only satisfied chemical stability in both water and phosphate buffered saline (PBS), but also excellent biocompatibility. Notably, BP nanosheet endows the prepared BP@ZIF-8 with prominent photothermal conversion efficiency (31.90%). Besides passivation BP, ZIF-8 provides the BP@ZIF-8 with high drug loading amount (1353.3 mg g-1). Moreover, the loaded drug can be controlled release by pH stimuli. Both in vitro and in vivo researches verified the resulted BP@ZIF-8 an ideal candidate for tumor multimodal treatments.
Asunto(s)
Antineoplásicos/uso terapéutico , Portadores de Fármacos/química , Estructuras Metalorgánicas/química , Nanoestructuras/química , Neoplasias/tratamiento farmacológico , Fósforo/química , Animales , Antineoplásicos/química , Línea Celular Tumoral , Terapia Combinada , Doxorrubicina/química , Doxorrubicina/uso terapéutico , Portadores de Fármacos/efectos de la radiación , Portadores de Fármacos/toxicidad , Liberación de Fármacos , Quimioterapia , Femenino , Humanos , Concentración de Iones de Hidrógeno , Rayos Infrarrojos , Estructuras Metalorgánicas/efectos de la radiación , Estructuras Metalorgánicas/toxicidad , Ratones , Nanoestructuras/efectos de la radiación , Nanoestructuras/toxicidad , Fósforo/efectos de la radiación , Fósforo/toxicidad , Terapia FototérmicaRESUMEN
The synergistic nanotheranostics of reactive oxygen species (ROS) augment or phototherapy has been a promising method within synergistic oncotherapy. However, it is still hindered by sophisticated design and fabrication, lack of a multimodal synergistic effect, and hypoxia-associated poor photodynamic therapy (PDT) efficacy. Herein, a kind of porous shuttle-shape platinum (IV) methylene blue (Mb) coordination polymer nanotheranostics-loaded 10-hydroxycamptothecin (CPT) is fabricated to address the abovementioned limitations. Our nanoreactors possess spatiotemporally controlled O2 self-supply, self-sufficient singlet oxygen (1O2), and outstanding photothermal effect. Once they are taken up by tumor cells, nanoreactors as a cascade catalyst can efficiently catalyze degradation of the endogenous hydrogen peroxide (H2O2) into O2 to alleviate tumor hypoxia. The production of O2 can ensure enhanced PDT. Subsequently, under both stimuli of external red light irradiation and internal lysosomal acidity, nanoreactors can achieve the on-demand release of CPT to augment in situ mitochondrial ROS and highly efficient tumor ablation via phototherapy. Moreover, under the guidance of near-infrared (NIR) fluorescent imaging, our nanoreactors exhibit strongly synergistic potency for treatment of hypoxic tumors while reducing damages against normal tissues and organs. Collectively, shuttle-shape platinum-coordinated nanoreactors with augmented ROS capacity and enhanced phototherapy efficiency can be regarded as a novel tumor theranostic agent and further promote the research of synergistic oncotherapy.
Asunto(s)
Antineoplásicos/uso terapéutico , Camptotecina/análogos & derivados , Portadores de Fármacos/química , Nanoestructuras/química , Neoplasias/tratamiento farmacológico , Hipoxia Tumoral/efectos de los fármacos , Animales , Antineoplásicos/química , Camptotecina/química , Camptotecina/uso terapéutico , Catálisis/efectos de la radiación , Línea Celular Tumoral , Portadores de Fármacos/efectos de la radiación , Liberación de Fármacos , Femenino , Humanos , Peróxido de Hidrógeno/química , Peróxido de Hidrógeno/metabolismo , Luz , Azul de Metileno/análogos & derivados , Azul de Metileno/efectos de la radiación , Ratones Endogámicos BALB C , Nanoestructuras/efectos de la radiación , Neoplasias/metabolismo , Oxígeno/metabolismo , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/uso terapéutico , Terapia Fototérmica , Platino (Metal)/química , Platino (Metal)/efectos de la radiación , Polímeros/síntesis química , Polímeros/química , Polímeros/efectos de la radiación , Porosidad , Oxígeno Singlete/metabolismo , Nanomedicina TeranósticaRESUMEN
Cyclodextrins (CDs), as pharmaceutical excipients with excellent biocompatibility, non-immunogenicity, and low toxicity in vivo, are widely used to carry drugs by forming inclusion complexes for improving the solubility and stability of drugs. However, the limited space of CDs' lipophilic central cavity affects the loading of many drugs, especially with larger molecules. In this study, ß-CDs were modified by acetonization to improve the affinity for the chemotherapy drug doxorubicin (DOX), and doxorubicin-adsorbing acetalated ß-CDs (Ac-CD:DOX) self-assembled to nanoparticles, followed by coating with the amphiphilic zinc phthalocyanine photosensitizer ZnPc-(PEG)5 for antitumor therapy. The final product ZnPc-(PEG)5:Ac-CD:DOX was demonstrated to have excellent stability and pH-sensitive drug release characteristics. The cell viability and apoptosis assay showed synergistic cytotoxic effects of chemotherapy and phototherapy. The mechanism of cytotoxicity was analyzed in terms of intracellular reactive oxygen species, mitochondrial membrane potential, and subcellular localization. More importantly, in vivo experiments indicated that ZnPc-(PEG)5:Ac-CD:DOX possessed significant tumor targeting, prominent antitumor activity, and less side effects. Our strategy expands the application of CDs as drug carriers and provides new insights into the development of CD chemistry.
Asunto(s)
Antineoplásicos/uso terapéutico , Doxorrubicina/uso terapéutico , Portadores de Fármacos/uso terapéutico , Nanopartículas/uso terapéutico , Neoplasias/tratamiento farmacológico , Animales , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Doxorrubicina/química , Portadores de Fármacos/síntesis química , Portadores de Fármacos/efectos de la radiación , Liberación de Fármacos , Sinergismo Farmacológico , Células Hep G2 , Humanos , Concentración de Iones de Hidrógeno , Indoles/síntesis química , Indoles/efectos de la radiación , Indoles/uso terapéutico , Isoindoles , Luz , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones , Mitocondrias/efectos de los fármacos , Nanopartículas/química , Nanopartículas/efectos de la radiación , Compuestos Organometálicos/síntesis química , Compuestos Organometálicos/efectos de la radiación , Compuestos Organometálicos/uso terapéutico , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/efectos de la radiación , Fármacos Fotosensibilizantes/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo , Compuestos de Zinc , beta-Ciclodextrinas/síntesis química , beta-Ciclodextrinas/efectos de la radiación , beta-Ciclodextrinas/uso terapéuticoRESUMEN
Rationale: Insufficient penetration and accumulation of theranostic payloads in solid tumors greatly challenge the clinical translation of cancer nanomedicines. To address this challenge, we synthesized natural melanin-cored and doxorubicin-loaded perfluoropentane nanodroplets with good biocompatibility and self-assembling ability. Methods: We used an opto-acoustic synergistic irradiation (OASI) method that was effective at lower energy levels than ultrasound- or laser-only irradiation to safely vaporize the nanodroplets and to cavitate the generated microbubbles for mechanically enhancing intratumoral delivery. The delivered melanin and doxorubicin inside the tumors mediated secondary chemo-photothermal therapy under laser irradiation to fully kill cancer cells. Results:In vivo animal experiments demonstrated direct mechanical disruption of tumor structures (H&E staining), enhanced intratumoral penetration of melanin (photoacoustic imaging), and efficient intratumoral accumulation of doxorubicin (fluorescent imaging). Anti-tumor experiments demonstrated that the nanodroplets combined with OASI treatment and subsequent laser irradiation could efficiently eliminate melanoma tumors. Conclusion: Melanin-cored and doxorubicin-loaded perfluoropentane nanodroplets hold great promise for translational sono-chemo-photothermal cancer therapy.
Asunto(s)
Doxorrubicina/administración & dosificación , Portadores de Fármacos/efectos de la radiación , Microburbujas/uso terapéutico , Neoplasias/terapia , Nanomedicina Teranóstica/métodos , Animales , Línea Celular Tumoral , Portadores de Fármacos/química , Femenino , Fluorocarburos/química , Humanos , Hipertermia Inducida/métodos , Terapia por Láser/métodos , Melaninas/química , Melaninas/efectos de la radiación , Ratones , Nanopartículas/química , Nanopartículas/efectos de la radiación , Neoplasias/diagnóstico por imagen , Neoplasias/patología , Técnicas Fotoacústicas/métodos , Fotoquimioterapia/métodos , Terapia por Ultrasonido/métodos , Volatilización/efectos de la radiación , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Erythrocyte-derived particles activated by near-infrared (NIR) light present a platform for various phototheranostic applications. We have engineered such a platform with indocyanine green as the NIR-activated agent. A particular feature of these particles is that their diameters can be tuned from micro- to nanoscale, providing a potential capability for broad clinical utility ranging from vascular to cancer-related applications. An important issue related to clinical translation of these particles is their immunogenic effects. Herein, we have evaluated the early-induced innate immune response of these particles in healthy Swiss Webster mice following tail vein injection by measurements of specific cytokines in blood serum, the liver, and the spleen following euthanasia. In particular, we have investigated the effects of particle size and relative dose, time-dependent cytokine response for up to 6 h postinjection, functionalization of the nanosized particles with folate or Herceptin, and dual injections of the particles 1 week apart. Mean concentrations of interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α, and monocyte chemoattractant protein (MCP)-1 in response to injection of microsized particles at the investigated relative doses were significantly lower than the corresponding mean concentrations induced by lipopolysaccharide (positive control) at 2 h. All investigated doses of the nanosized particles induced significantly higher concentrations of MCP-1 in the liver and the spleen as compared to phosphate buffer saline (PBS) (negative control) at 2 h. In response to micro- and nanosized particles at the highest investigated dose, there were significantly higher levels of TNF-α in blood serum at 2 and 6 h postinjection as compared to the levels associated with PBS treatment at these times. Whereas the mean concentration of TNF-α in the liver significantly increased between 2 and 6 h postinjection in response to the injection of the microsized particles, it was significantly reduced during this time interval in response to the injection of the nanosized particles. In general, functionalization of the nanosized particles was associated with a reduction of IL-6 and MCP-1 in blood serum, the liver, and the spleen, and TNF-α in blood serum. With the exception of IL-10 in the spleen in response to nanosized particles, the second injection of micro- or nanosized particles did not lead to significantly higher concentrations of other cytokines at the investigated dose as compared to a single injection.
Asunto(s)
Portadores de Fármacos/efectos adversos , Eritrocitos/química , Inmunidad/efectos de los fármacos , Fototerapia/métodos , Nanomedicina Teranóstica/métodos , Animales , Citocinas/análisis , Citocinas/metabolismo , Relación Dosis-Respuesta Inmunológica , Esquema de Medicación , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/química , Portadores de Fármacos/efectos de la radiación , Eritrocitos/inmunología , Femenino , Rayos Infrarrojos , Inyecciones Intravenosas , Lipopolisacáridos/administración & dosificación , Lipopolisacáridos/inmunología , Hígado/efectos de los fármacos , Hígado/inmunología , Hígado/metabolismo , Ratones , Modelos Animales , Nanopartículas/administración & dosificación , Nanopartículas/efectos adversos , Nanopartículas/química , Nanopartículas/efectos de la radiación , Tamaño de la Partícula , Fototerapia/efectos adversos , Bazo/efectos de los fármacos , Bazo/inmunología , Bazo/metabolismoRESUMEN
The limited tumor tissue penetration of many nanoparticles remains a formidable challenge to their therapeutic efficacy. Although several photonanomedicines have been applied to improve tumor penetration, the first near-infrared window mediated by the low optical tissue penetration depth severely limits their anticancer effectiveness. To achieve deep optical tissue and drug delivery penetration, a near-infrared second window (NIR-II)-excited and pH-responsive ultrasmall drug delivery nanoplatform was fabricated based on BSA-stabilized CuS nanoparticles (BSA@CuS NPs). The BSA@CuS NPs effectively encapsulated doxorubicin (DOX) via strong electrostatic interactions to form multifunctional nanoparticles (BSA@CuS@DOX NPs). The BSA@CuS@DOX NPs had an ultrasmall size, which allowed them to achieve deeper tumor penetration. They also displayed stronger NIR II absorbance-mediated deep optical tissue penetration than that of the NIR I window. Moreover, the multifunctional nanoplatform preferentially accumulated in tumor sites, induced tumor hyperthermia, and generated remarkably high ROS levels in tumor sites upon NIR-II laser (1064 nm) irradiation. More importantly, our strategy achieved excellent synergistic effects of chemotherapy and phototherapy (chemophototherapy) under the guidance of photothermal imaging. The developed nanoparticles also showed good biocompatibility and bioclearance properties. Therefore, our work demonstrated a facile strategy for fabricating a multifunctional nanoplatform that is a promising candidate for deep tumor penetration as an effective antitumor therapy.
Asunto(s)
Doxorrubicina/administración & dosificación , Portadores de Fármacos/efectos de la radiación , Nanopartículas/efectos de la radiación , Neoplasias/tratamiento farmacológico , Fototerapia/métodos , Animales , Línea Celular Tumoral/trasplante , Supervivencia Celular , Modelos Animales de Enfermedad , Doxorrubicina/farmacocinética , Portadores de Fármacos/química , Liberación de Fármacos/efectos de la radiación , Humanos , Concentración de Iones de Hidrógeno , Rayos Infrarrojos , Rayos Láser , Ratones , Nanopartículas/química , Neoplasias/patología , Fototerapia/instrumentación , Distribución TisularRESUMEN
With the development of nanotechnology, Tumor Physical Stimuli-Responsive Therapies (TPSRTs) have reached a new stage because of the remarkable characteristics of nanocarriers. The nanocarriers enable such therapies to overcome the drawbacks of traditional therapies, such as radiotherapy or chemotherapy. To further explore the possibility of the nanocarrier-assisted TPSRTs, scientists have combined different TPSRTs via; the platform of nanocarriers into combination TPSRTs, which include Photothermal Therapy (PTT) with Magnetic Hyperthermia Therapy (MHT), PTT with Sonodynamic Therapy (SDT), MHT with Photodynamic Therapy (PDT), and PDT with PTT. To achieve such therapies, it requires to fully utilize the versatile functions of a specific nanocarrier, which depend on a pellucid understanding of the traits of those nanocarriers. This review covers the principles of different TPSRTs and their combinations, summarizes various types of combination TPSRTs nanocarriers and their therapeutic effects on tumors, and discusses the current disadvantages and future developments of these nanocarriers in the application of combination TPSRTs.
Asunto(s)
Antineoplásicos/administración & dosificación , Portadores de Fármacos/efectos de la radiación , Nanopartículas/efectos de la radiación , Neoplasias/terapia , Nanomedicina Teranóstica/métodos , Animales , Antineoplásicos/farmacocinética , Línea Celular Tumoral , Portadores de Fármacos/química , Liberación de Fármacos/efectos de la radiación , Humanos , Luz , Magnetoterapia/métodos , Magnetoterapia/tendencias , Ratones , Nanopartículas/química , Neoplasias/patología , Fotoquimioterapia/métodos , Fotoquimioterapia/tendencias , Terapia Fototérmica/métodos , Nanomedicina Teranóstica/tendencias , Terapia por Ultrasonido/métodos , Terapia por Ultrasonido/tendencias , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Small interfering RNA (siRNA)-induced gene therapy has been recognized as a promising avenue for effective cancer treatment, while easy enzymatic degradation, poor transfection efficiency, nonspecific biodistribution, and uncontrolled release hinder its extensive clinical applications. Zeolitic imidazolate frameworks-8 (ZIF-8) have emerged as promising drug carriers without an in-depth exploration in programmable siRNA delivery. Herein, we report a multifunctional PDAs-ZIF-8 (PZ) nanoplatform for delivering siRNA with combined photothermal therapy (PTT) and gene therapy (GT) via the noninvasive guidance of photoacoustic (PA)/near-infrared (IR) dual-modal imaging. The ingenious PZ nanocarriers mediated the tumor-specific accumulation of therapeutic siRNA without undesired degradation and preleakage. The pH-responsive ZIF-8 decomposed in an acidic tumor microenvironment that was accompanied by the release of siRNA payloads for cleaving target mRNA in gene silencing therapy. Meanwhile, the polydopamine nanoparticles (PDAs) could simultaneously serve as a powerful noninvasive PA/IR imaging contrast agent and versatile photothermal agent for diagnosis-guided photogenetherapy. The systematic in vitro and in vivo experimental explorations demonstrated that our PDAs-siRNA-ZIF-8 (PSZ) could greatly enhance the therapeutic efficiency as compared with the corresponding PTT or GT monotherapy. This work holds great potential to advance the development of more intelligent diagnosis and therapeutic strategies, thus supplying promising smart nanomedicines in the near future.
Asunto(s)
Antineoplásicos/uso terapéutico , Medios de Contraste/química , Portadores de Fármacos/química , Nanopartículas/química , Neoplasias/tratamiento farmacológico , ARN Interferente Pequeño/uso terapéutico , Animales , Terapia Combinada/métodos , Medios de Contraste/efectos de la radiación , Portadores de Fármacos/efectos de la radiación , Silenciador del Gen/efectos de los fármacos , Terapia Genética , Hipertermia Inducida/métodos , Indoles/química , Indoles/efectos de la radiación , Rayos Infrarrojos , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/efectos de la radiación , Ratones Endogámicos BALB C , Nanopartículas/efectos de la radiación , Fototerapia/métodos , Polímeros/química , Polímeros/efectos de la radiación , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
PURPOSE: The aim of the present study was to develop a new strategy for combined thermo-chemotherapy of cancer. For this purpose, we used ultrasound waves [1 MHz; 1 W/cm2; 10 min] in combination with a sonosensitizing nanoplatform, named ACA, made of alginate co-loaded with cisplatin and gold nanoparticles (AuNPs). METHODS: Various combinatorial treatment regimens consisting of ultrasound, AuNPs, cisplatin, and ACA nanoplatform were studied in vivo. The CT26 colon adenocarcinoma cell line was used for tumor induction in BALB/c mice. During the ultrasound exposure, we monitored the temperature variations in each treatment group using infrared thermal imaging. Furthermore, tumor metabolism was assessed by [18F]FDG (2-deoxy-2-[18F]fluoro-D-glucose)-positron emission tomography (PET) imaging. RESULTS: The combination of ultrasound with nanoplatform showed an improved therapeutic efficacy than free cisplatin or ultrasound alone. It was revealed that the examined thermo-chemotherapy protocol has the potential to intensively decrease the metabolic activity of CT26 tumors. CONCLUSIONS: The data obtained in this study confirmed a potent anti-tumor efficacy caused by the ACA nanoplatform and ultrasound combination. It may provide a beneficial cancer therapy strategy in which the thermal and mechanical effects of ultrasound can intensify the therapeutic ratio of conventional chemotherapy methods.
Asunto(s)
Cisplatino/administración & dosificación , Portadores de Fármacos/efectos de la radiación , Hipertermia Inducida/métodos , Neoplasias/terapia , Terapia por Ultrasonido/métodos , Alginatos/química , Animales , Línea Celular Tumoral , Terapia Combinada/métodos , Portadores de Fármacos/química , Composición de Medicamentos/métodos , Fluorodesoxiglucosa F18/administración & dosificación , Oro/química , Humanos , Masculino , Nanopartículas del Metal/química , Ratones , Ratones Endogámicos BALB C , Neoplasias/diagnóstico por imagen , Neoplasias/patología , Tomografía de Emisión de Positrones/métodos , Resultado del Tratamiento , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
A novel coreshell type thermonanoparticle (CSTNP) coloaded with temozolomide (TMZ) and the fluorescein new indocyanine green dye IR820 (termed ITCSTNPs) was designed and combined with a nearinfrared (NIR) laser to realize its photothermal conversion. The ITCSTNPs were prepared using a twostep synthesis method and comprised a thermosensitive shell and a biodegradable core. IR820 and TMZ were entrapped in the shell and the core, respectively. Dynamic light scattering results demonstrated that the average hydrodynamic size of the ITCSTNPs was 196.4±3.1 nm with a ζ potential of 24.9±1.3 mV. The encapsulation efficiencies of TMZ and IR820 were 6.1 and 16.6%, respectively. Temperature increase curves under NIR laser irradiation indicated that the ITCSTNPs exhibited the desired photothermal conversion efï¬ciency. The in vitro drug release curves revealed a suitable release capability of ITCSTNP under physiological conditions, whereas NIR laser irradiation accelerated the drug release. Inverted fluorescence microscopy and flow cytometry results revealed that the uptake of ITCSTNPs by A375 melanoma cells occurred in a concentrationdependent manner. Confocal laser scanning microscopy results indicated that ITCSTNPs entered tumour cells via endocytosis and were located in intercellular lysosomes. In summary, the present study explored the photothermal conversion capability, cellular uptake, and intracellular localization of ITCSTNPs.
Asunto(s)
Antineoplásicos Alquilantes/administración & dosificación , Portadores de Fármacos/química , Hipertermia Inducida/métodos , Melanoma/terapia , Neoplasias Cutáneas/terapia , Temozolomida/administración & dosificación , Antineoplásicos Alquilantes/farmacocinética , Línea Celular Tumoral , Terapia Combinada/métodos , Portadores de Fármacos/efectos de la radiación , Liberación de Fármacos/efectos de la radiación , Dispersión Dinámica de Luz , Endocitosis/efectos de la radiación , Humanos , Hipertermia Inducida/instrumentación , Verde de Indocianina/administración & dosificación , Verde de Indocianina/análogos & derivados , Rayos Láser , Melanoma/patología , Nanopartículas/química , Nanopartículas/efectos de la radiación , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Neoplasias Cutáneas/patología , Temozolomida/farmacocinéticaRESUMEN
The near-infrared dye, IR780 iodide, has been utilized in photodynamic therapy (PDT) and photothermal therapy (PTT). However, the hydrophobicity and photosensitivity of IR780 limit its further applications in biomedical fields. Herein, the hydrophilic sericin was modified with hydrophobic cholesterol to form an amphiphilic macromolecular conjugate (Ser-Chol). The tumor-targeting agent, folic acid (FA), was further linked to the conjugate (FA-Ser-Chol). The IR780 could be encapsulated into such amphiphilic macromolecule to form stable micelles (FA-Ser-Chol/IR780) by self-assembly, and the solubility and photo-stability of IR780 were greatly improved. The FA-Ser-Chol/IR780 micelles could be efficiently absorbed by FA-positive gastric cancer cells (BGC-823) through FA receptors, while the uptake micelles showed remarkable PDT and PTT cytotoxicity towards BGC-823 cells under laser irradiation of 808â¯nm. Therefore, FA-Ser-Chol micelles may serve as a promising IR780 carrier for PDT and PTT therapy.
Asunto(s)
Antineoplásicos/administración & dosificación , Portadores de Fármacos/administración & dosificación , Micelas , Nanopartículas/administración & dosificación , Fototerapia , Sericinas/administración & dosificación , Antineoplásicos/efectos de la radiación , Línea Celular Tumoral , Portadores de Fármacos/efectos de la radiación , Ácido Fólico/administración & dosificación , Humanos , Indoles/administración & dosificación , Rayos Láser , Nanopartículas/efectos de la radiación , Sericinas/efectos de la radiación , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/metabolismoRESUMEN
Bacterial biofilms are widely associated with persistent infections and food contamination. High resistance to conventional antimicrobial agents resulted in an urgent need for novel formulation to eliminate these bacterial communities. Herein we fabricated light controllable chitosan micelles loading with thymol (T-TCP) for elimination of biofilm. Due to the exterior chitosan, T-TCP micelles easily bind to negative biofilm through electrostatic interaction and efficiently deliver the essential oil payloads. Under irradiation, T-TCP micelles generated ROS, which triggered simultaneous thymol release and also resulted in additional ROS-inducing bactericidal effects, both effectively eradicating biofilms of Listeria monocytogenes and Staphylococcus aureus. This formulation provided a platform for other water-insoluble antimicrobials and might be used as a potent and controllable solution to biofilm fighting.
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Biopelículas/efectos de los fármacos , Quitosano/análogos & derivados , Quitosano/química , Portadores de Fármacos/química , Micelas , Timol/farmacología , Quitosano/síntesis química , Quitosano/efectos de la radiación , Portadores de Fármacos/síntesis química , Portadores de Fármacos/efectos de la radiación , Liberación de Fármacos/efectos de la radiación , Interacciones Hidrofóbicas e Hidrofílicas , Luz , Listeria monocytogenes/fisiología , Aceites Volátiles/farmacología , Polímeros/síntesis química , Polímeros/química , Polímeros/efectos de la radiación , Especies Reactivas de Oxígeno , Staphylococcus aureus/fisiología , Sulfuros/síntesis química , Sulfuros/química , Sulfuros/efectos de la radiación , Cloruro de Tolonio/síntesis química , Cloruro de Tolonio/química , Cloruro de Tolonio/efectos de la radiaciónRESUMEN
Ascribe to the unique two-dimensional planar nanostructure with exceptional physical and chemical properties, black phosphorous (BP) as the emerging inorganic twodimensional nanomaterial with high biocompatibility and degradability has been becoming one of the most promising materials of great potentials in biomedicine. The exfoliated BP sheets possess ultra-high surface area available for valid bio-conjugation and molecular loading for chemotherapy. Utilizing the intrinsic near-infrared optical absorbance, BPbased photothermal therapy in vivo, photodynamic therapy and biomedical imaging has been realized, achieving unprecedented anti-tumor therapeutic efficacy in animal experiments. Additionally, the BP nanosheets can strongly react with oxygen and water, and finally degrade to non-toxic phosphate and phosphonate in the aqueous solution. This manuscript aimed to summarize the preliminary progresses on theranostic application of BP and its derivatives black phosphorus quantum dots (BPQDs), and discussed the prospects and the state-of-art unsolved critical issues of using BP-based material for theranostic applications.
Asunto(s)
Fósforo/uso terapéutico , Puntos Cuánticos/uso terapéutico , Animales , Técnicas Biosensibles/métodos , Línea Celular Tumoral , Portadores de Fármacos/química , Portadores de Fármacos/efectos de la radiación , Portadores de Fármacos/uso terapéutico , Portadores de Fármacos/toxicidad , Humanos , Luz , Neoplasias/tratamiento farmacológico , Neoplasias/terapia , Imagen Óptica/métodos , Fósforo/química , Fósforo/efectos de la radiación , Fósforo/toxicidad , Puntos Cuánticos/química , Puntos Cuánticos/efectos de la radiación , Puntos Cuánticos/toxicidad , Nanomedicina Teranóstica/métodosRESUMEN
In this Article, we show that the surface of the bacteriophage Qß is equipped with natural ligands for the synthesis of small gold nanoparticles (AuNPs). By exploiting disulfides in the protein secondary structure and the geometry formed from the capsid quaternary structure, we find that we can produce regularly arrayed patterns of â¼6 nm AuNPs across the surface of the virus-like particle. Experimental and computational analyses provide insight into the formation and stability of this composite. We further show that the entrapped genetic material can hold upward of 500 molecules of the anticancer drug Doxorubicin without leaking and without interfering with the synthesis of the AuNPs. This direct nucleation of nanoparticles on the capsid allows for exceptional conduction of photothermal energy upon nanosecond laser irradiation. As a proof of principle, we demonstrate that this energy is capable of rapidly releasing the drug from the capsid without heating the bulk solution, allowing for highly targeted cell killing in vitro.
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Allolevivirus/química , Antineoplásicos/farmacología , Doxorrubicina/farmacología , Portadores de Fármacos/química , Oro/química , Nanopartículas del Metal/química , Células A549 , Animales , Antineoplásicos/química , Cápside/química , Proteínas de la Cápside/química , Doxorrubicina/química , Portadores de Fármacos/efectos de la radiación , Portadores de Fármacos/toxicidad , Liberación de Fármacos , Oro/efectos de la radiación , Oro/toxicidad , Humanos , Hipertermia Inducida/métodos , Luz , Nanopartículas del Metal/efectos de la radiación , Nanopartículas del Metal/toxicidad , Ratones , Tamaño de la Partícula , Fototerapia/métodos , Porosidad , Prueba de Estudio Conceptual , Células RAW 264.7 , ARN/química , ARN/toxicidadRESUMEN
Two-dimensional (2D) MXenes have emerged as a promising planar theranostic nanoplatform for versatile biomedical applications; but their in vivo behavior and performance has been severely influenced and hindered by a lack of necessary surface chemistry for adequate surface engineering. To solve this critical issue, this work employs versatile sol-gel chemistry for the construction of a unique "therapeutic mesopore" layer onto the surface of 2D niobium carbide (Nb2C) MXene. Methods: The in situ self-assembled mesopore-making agent (cetanecyltrimethylammonium chloride, in this case) was kept within the mesopores for efficient chemotherapy. The abundant surface saline chemistry of mesoporous silica-coated Nb2C MXene was further adopted for stepwise surface engineering including PEGylation and conjugation with cyclic arginine-glycine-aspartic pentapeptide c(RGDyC) for targeted tumor accumulation. Results: 2D Nb2C MXenes were chosen based on their photothermal conversion capability (28.6%) in the near infrared (NIR)-II biowindow (1064 nm) for enhanced photothermal hyperthermia. Systematic in vitro and in vivo assessments demonstrate targeted and enhanced chemotherapy and photothermal hyperthermia of cancer (U87 cancer cell line and corresponding tumor xenograft; inhibition efficiency: 92.37%) in the NIR-II biowindow by these mesopore-coated 2D Nb2C MXenes. Conclusion: This work not only significantly broadens the biomedical applications of 2D Nb2C MXene for enhanced cancer therapy, but also provides an efficient strategy for surface engineering of 2D MXenes to satisfy versatile application requirements.
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Portadores de Fármacos/farmacocinética , Radiación Electromagnética , Glioblastoma/terapia , Hipertermia Inducida/métodos , Terapia Molecular Dirigida/métodos , Niobio/farmacocinética , Fototerapia/métodos , Animales , Línea Celular Tumoral , Portadores de Fármacos/síntesis química , Portadores de Fármacos/efectos de la radiación , Xenoinjertos , Ratones , Trasplante de Neoplasias , Neoplasias Experimentales/terapia , Niobio/efectos de la radiación , Propiedades de Superficie , Resultado del TratamientoRESUMEN
Chemo-photothermal therapy shows great potential for inhibiting tumor growth. However, achieving maximal chemo-photothermal synergistic efficacy is challenging because of the low efficiency of controllable chemo-drug release in response to external or internal triggers. Thus, a nano-delivery system that could effectively achieve photothermal therapy and dual stimuli-responsive (heat and pH) drug release to inhibit both primary breast tumor growth and metastases is required. Methods: Herein, a thermo- and pH-responsive polymer (mPEG-PAAV) with an upper critical solution temperature (UCST) was synthesized to fabricate a DOX- and IR780-loaded micellar system. After systematic studies of the photothermal performance and controllable drug release of mPEG-PAAV micelles/IR780+DOX under NIR irradiation at different pH values, their chemo-photothermal synergetic therapy efficacies were also estimated both in in vitro and in vivo. Results: Because of the photothermal conversion of mPEG-PAAV micelle/IR780+DOX (~200 nm, 3.82 mV), high local temperature could be induced at the tumor site under NIR laser irradiation. This hyperthermia not only produced an enhanced tumor necrosis, but also broke down the micelles under the decreased pH environment, resulting in rapid DOX release and enhanced intracellular drug accumulation after NIR laser irradiation. In addition, photoacoustic imaging (PAI) of mPEG-PAAV/IR780+DOX micelle was adopted to monitor the morphology and micro-vascular distribution of the tumor tissue, which could also guide the chemo-photothermal therapy. Most importantly, the systemic administration of mPEG-PAAV micelles/IR780+DOX combined with NIR laser irradiation could simultaneously eliminate the 4T1 breast tumor and thoroughly suppress lung metastasis without any obvious adverse effects. Conclusion: Herein, a pH- and thermo-dual responsive UCST micelle system was developed for delivering IR780 and DOX, which could achieve NIR laser-controlled drug release and PA imaging guidance for chemo-photothermal synergistic therapy of both primary breast tumors and their metastases.
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Neoplasias de la Mama/terapia , Portadores de Fármacos/administración & dosificación , Quimioterapia/métodos , Hipertermia Inducida/métodos , Nanoestructuras/administración & dosificación , Técnicas Fotoacústicas/métodos , Fototerapia/métodos , Animales , Neoplasias de la Mama/secundario , Terapia Combinada/métodos , Modelos Animales de Enfermedad , Doxorrubicina/administración & dosificación , Portadores de Fármacos/efectos de la radiación , Concentración de Iones de Hidrógeno , Indoles/administración & dosificación , Rayos Infrarrojos , Ratones Endogámicos BALB C , Micelas , Nanoestructuras/efectos de la radiación , Polímeros/administración & dosificación , Polímeros/efectos de la radiación , TemperaturaRESUMEN
A biodegradable drug delivery system (DDS) is one the most promising therapeutic strategies for cancer therapy. Here, we propose a unique concept of light activation of black phosphorus (BP) at hydrogel nanostructures for cancer therapy. A photosensitizer converts light into heat that softens and melts drug-loaded hydrogel-based nanostructures. Drug release rates can be accurately controlled by light intensity, exposure duration, BP concentration, and hydrogel composition. Owing to sufficiently deep penetration of near-infrared (NIR) light through tissues, our BP-based system shows high therapeutic efficacy for treatment of s.c. cancers. Importantly, our drug delivery system is completely harmless and degradable in vivo. Together, our work proposes a unique concept for precision cancer therapy by external light excitation to release cancer drugs. If these findings are successfully translated into the clinic, millions of patients with cancer will benefit from our work.
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Antineoplásicos/administración & dosificación , Preparaciones de Acción Retardada/administración & dosificación , Portadores de Fármacos/efectos de la radiación , Sistemas de Liberación de Medicamentos/métodos , Nanoestructuras/efectos de la radiación , Neoplasias/tratamiento farmacológico , Animales , Antineoplásicos/química , Línea Celular Tumoral , Preparaciones de Acción Retardada/química , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos/instrumentación , Humanos , Hidrogeles/química , Hidrogeles/efectos de la radiación , Rayos Infrarrojos , Ratones , Ratones Desnudos , Nanoestructuras/química , Fósforo/químicaRESUMEN
Cancer metastasis is responsible for over 90% of breast cancer-related deaths, and inhibiting lymph node metastasis is an option to treat metastatic disease. Herein, we report the use of IR-780-loaded polymeric micelles (IPMs) for effective photothermal therapy (PTT) of breast cancer lymphatic metastasis. The IPMs were nanometer-sized micelles with a mean diameter of 25.6 nm and had good stability in simulated physiological solutions. Under 808-nm laser irradiation, IPMs exhibited high heat-generating capability in both in vitro and in vivo experiments. After intravenous injection, IPMs specifically accumulated in the tumor and metastatic lymph nodes and penetrated into these tissues. Moreover, a single IPMs treatment plus laser irradiation significantly inhibited primary tumor growth and suppressed lymphatic metastasis by 88.2%. Therefore, IPMs are an encouraging platform for PTT applications in treatment of metastatic breast cancer.
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Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Indoles/uso terapéutico , Metástasis Linfática/prevención & control , Animales , Antineoplásicos/efectos de la radiación , Línea Celular Tumoral , Portadores de Fármacos/química , Portadores de Fármacos/efectos de la radiación , Portadores de Fármacos/uso terapéutico , Femenino , Calefacción , Indoles/efectos de la radiación , Terapia por Láser/métodos , Ratones Desnudos , Micelas , Tamaño de la Partícula , Fosfatidiletanolaminas/química , Fosfatidiletanolaminas/efectos de la radiación , Fosfatidiletanolaminas/uso terapéutico , Fototerapia/métodos , Polietilenglicoles/química , Polietilenglicoles/efectos de la radiación , Polietilenglicoles/uso terapéuticoRESUMEN
How to encapsulate and transport the payload of multiple therapeutic compounds avoiding premature leakage, and simultaneously co-release them rapidly at specific lesions still remains the major concern in clinic. Herein, we designed the UCN@mSiO2-(Azo+RB) (azobenzene groups and Rose Bengal) nanoimpellers, which used the multicolor-emission capability of the core-shell upconverting nanoparticles (UCNs) at a single excitation wavelength to co-release anticarcinogen doxorubicin (Dox) and reactive oxygen species (ROS) for combined chemotherapy and photodynamic therapy (PDT). The nanoimpeller was formed from UCN inner core, mesoporous silica shell, and light triggers Azo and RB molecules. The UCNs emitting UV/blue and green/red multiband light were used to activate the photoresponsive Azo and photosensitizer RB molecules; The mesoporous silica shell offered the possibilities to load anticancer drug and conjugate the light triggers; As there are strong charge interaction and hydrogen bonds between Dox and surface silanols of mesoporous silica, the azobenzene molecules worked as "gatekeeper" and "molecular stirrer" to precisely trap and propel the release of Dox under the external stimuli. The time-dependent drug release analysis, ROS production test and PDT test suggested that the nanoparticles may serve as a useful multifunctional nanoplatform for synergistic therapy and cancer diagnostic.
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Doxorrubicina/química , Portadores de Fármacos/química , Rayos Infrarrojos , Nanopartículas/química , Especies Reactivas de Oxígeno/metabolismo , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/metabolismo , Antibióticos Antineoplásicos/toxicidad , Compuestos Azo/química , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/metabolismo , Doxorrubicina/toxicidad , Portadores de Fármacos/efectos de la radiación , Liberación de Fármacos , Sinergismo Farmacológico , Células HeLa , Humanos , Nanopartículas/efectos de la radiación , Nanopartículas/toxicidad , Fármacos Fotosensibilizantes/química , Rosa Bengala/química , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
A medical nanoplatform with small size, low cost, biocompatibility, good biodegradability, and, in particular, multifunctionality has attracted much attention in the exploration of novel therapeutic methodologies. As an emerging material of self-assembled porous structure, metal-organic frameworks (MOFs) have high expectations because of their special properties compared to traditional porous materials. Therefore, integration of MOFs and functional materials is leading to the creation of new multifunctional composites/hybrids. Photothermal therapy (PTT), using near-IR (NIR) laser-absorbing nanomaterials as PTT agents, has shown encouraging therapeutic effects to photothermally ablate tumors. However, the most of widely used PTT agents are inorganic materials and nonbiodegradable. Herein, uniform polypyrrole (PPy) nanoparticles (NPs) with good biodegradability were synthesized by a microemulsion method. The PPy NPs were further coated with the mesoporous iron-based MOF structure MIL-100 by interaction between PPy NPs and MIL-100 precursors at room temperature. As a multifunctional nanoplatform, an anticancer drug could easily be loaded into the mesopores of the MIL-100 shell. The PPy core, as an organic photothermal agent, is able to photothermally ablate cancer cells and improve the efficacy of chemotherapy under NIR irradiation. The composites showed an outstanding in vivo synergistic anticancer capacity. Our work could encourage further study in the construction of a synergetic system using MOFs and organic PTT agents.