RESUMEN
Stimuli-responsive drug delivery carriers, particularly those exhibiting pH sensitivity, have attracted significant scholarly interest due to their promising potential in anticancer therapeutic applications. This phenomenon can primarily be ascribed to the inherently acidic nature of tumor microenvironments. However, pH-responsive carriers frequently require the incorporation of functional groups or materials sensitive to pH changes. Given the pH-sensitive characteristics of metal coordination with natural small-molecule drugs, organometallic supramolecules present a facile and effective strategy for integrating pH-responsive behavior into these systems. Meanwhile, utilizing the natural compound luteolin in conjunction with iron ions (Fe3+) through the advanced engineering technique of flash nanoprecipitation (FNP) results in the synthesis of stable, highly loaded nanoparticles (NPs) exhibiting a supramolecular photothermal effect. Our experimental findings substantiate that the photothermal effect persists over time, even after the pH-responsive release phase has ended. Consequently, these polymeric pH-responsive metallic supramolecular nanoparticles integrate chemotherapy and photothermal therapy, creating a synergistic approach to cancer treatment. This bifunctional platform, which exhibits both pH-responsive and photothermal properties, presents a highly promising avenue for biomedical applications, particularly in the area of tumor therapies. Its dual function offers a potentially efficacious approach to tumor treatment.
Asunto(s)
Nanopartículas del Metal , Concentración de Iones de Hidrógeno , Humanos , Nanopartículas del Metal/química , Polímeros/química , Antineoplásicos/química , Antineoplásicos/farmacología , Terapia Fototérmica/métodos , Portadores de Fármacos/química , Portadores de Fármacos/efectos de la radiación , Hierro/químicaRESUMEN
The unprecedented navigation ability in micro/nanoscale and tailored functionality tunes micro/nanomotors as new target drug delivery systems, open up new horizons for biomedical applications. Herein, we designed a light-driven rGO/Cu2 + 1O tubular nanomotor for active targeting of cancer cells as a drug delivery system. The propulsion performance is greatly enhanced in real cell media (5% glucose cells isotonic solution), attributing to the introduction of oxygen vacancy and reduced graphene oxide (rGO) layer for separating photo-induced electron-hole pairs. The motion speed and direction can be readily modulated. Meanwhile, doxorubicin (DOX) can be loaded quickly on the rGO layer because of π-π bonding effect. The Cu2 + 1O matrix in the tiny robots not only serves as a photocatalyst to generate a chemical concentration gradient as the driving force but also acts as a nanomedicine to kill cancer cells as well. The strong propulsion of light-driven rGO/Cu2 + 1O nanomotors coupled with tiny size endow them with active transmembrane transport, assisting DOX and Cu2 + 1O breaking through the barrier of the cell membrane. Compared with non-powered nanocarrier and free DOX, light-propelled rGO/Cu2 + 1O nanomotors exhibit greater transmembrane transport efficiency and significant therapeutic efficacy. This proof-of-concept nanomotor design presents an innovative approach against tumor, enlarging the list of biomedical applications of light-driven micro/nanomotors to the superficial tissue treatment.
Asunto(s)
Cobre , Doxorrubicina , Grafito , Luz , Cobre/química , Humanos , Doxorrubicina/farmacología , Doxorrubicina/química , Grafito/química , Sistemas de Liberación de Medicamentos , Portadores de Fármacos/química , Portadores de Fármacos/efectos de la radiación , Supervivencia Celular/efectos de los fármacos , Liberación de Fármacos , Antibióticos Antineoplásicos/farmacología , Antibióticos Antineoplásicos/química , Línea Celular TumoralRESUMEN
BACKGROUND: The purpose of this study was to investigate the protective effect of Silibinin-loaded polymeric micelles from human hair against UV-B radiation. METHODS: Eight formulations with different concentrations of Silibinin, Pluronic F-127, and Labrasol-Labrafil were made by a solvent evaporation method, and the selected formulation was chosen by examining their properties like particle size and loading efficiency. Six groups of human hair, including a group that received the selected formulation, were exposed to UV-B radiation and by calculating its factors such as peak-to-valley roughness, RMS roughness, FTIR, and the amount of protein loss, the protective effect of the selected formulation was judged. RESULTS: According to the results, the loading efficiency and particle size of the selected formulation were 45.34% and 43.19 nm. The Silibinin release profile had two parts, fast and slow, which were suitable for creating a drug depot on hair. Its zeta potential also confirmed the minimum electrostatic interference between the formulation and hair surface. The zeta potential of selected formulation was -5.9 mv. Examination of AFM images showed that the selected formulation was able to prevent the increase in peak-to-valley roughness and RMS roughness caused by UV-B radiation. RMS roughness after 600 h of UV radiation in Groups 5 and 6 was significantly lower than the negative control group and the amount of this factor did not differ significantly between 0 and 600, so it can be concluded that the selected formulation containing Silibinin and the positive control group was able to prevent the increase of RMS roughness and hair destruction. In other hands, the two positive control groups and the selected formulation containing Silibinin were able to effectively reduce hair protein loss. CONCLUSION: Silibinin-loaded polymeric micelles were able to effectively protect hair from structural and chemical changes caused by UV-B radiation.
Asunto(s)
Cabello , Micelas , Tamaño de la Partícula , Silibina , Rayos Ultravioleta , Humanos , Rayos Ultravioleta/efectos adversos , Silibina/farmacología , Silibina/administración & dosificación , Silibina/química , Cabello/efectos de los fármacos , Cabello/efectos de la radiación , Silimarina/farmacología , Silimarina/administración & dosificación , Silimarina/química , Polímeros/química , Liberación de Fármacos/efectos de la radiación , Antioxidantes/farmacología , Antioxidantes/administración & dosificación , Portadores de Fármacos/química , Portadores de Fármacos/efectos de la radiaciónRESUMEN
Integrating chemodynamic therapy (CDT) and photodynamic therapy (PDT) into one nanoplatform can produce much more reactive oxygen species (ROS) for tumor therapy. Nevertheless, it is still a great challenge to selectively generate sufficient ROS in tumor regions. Meanwhile, CDT and PDT are restricted by insufficient H2O2 content in the tumor as well as by the limited tumor tissue penetration of the light source. In this study, a smart pH/ROS-responsive nanoplatform, Fe2+@UCM-BBD, is rationally designed for tumor combination therapy. The acidic microenvironment can induce the pH-responsive release of doxorubicin (DOX), which can induce tumor apoptosis through DNA damage. Beyond that, DOX can promote the production of H2O2, providing sufficient materials for CDT. Of note, upconversion nanoparticles at the core can convert the 980 nm light to red and green light, which are used to activate Ce6 to produce singlet oxygen (1O2) and achieve upconversion luminescence imaging, respectively. Then, the ROS-responsive linker bis-(alkylthio)alkene is cleaved by 1O2, resulting in the release of Fenton reagent (Fe2+) to realize CDT. Taken together, Fe2+@UCM-BBD exhibits on-demand therapeutic reagent release capability, excellent biocompatibility, and remarkable tumor inhibition ability via synergistic chemo/photodynamic/chemodynamic combination therapy.
Asunto(s)
Antineoplásicos/uso terapéutico , Doxorrubicina/uso terapéutico , Portadores de Fármacos/uso terapéutico , Nanopartículas del Metal/uso terapéutico , Fármacos Fotosensibilizantes/uso terapéutico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Animales , Antineoplásicos/química , Línea Celular Tumoral , Clorofilidas/química , Clorofilidas/efectos de la radiación , Clorofilidas/uso terapéutico , Terapia Combinada , Doxorrubicina/química , Portadores de Fármacos/química , Portadores de Fármacos/efectos de la radiación , Liberación de Fármacos , Quimioterapia , Erbio/química , Erbio/efectos de la radiación , Erbio/uso terapéutico , Femenino , Fluoruros/química , Fluoruros/efectos de la radiación , Fluoruros/uso terapéutico , Humanos , Hierro/química , Hierro/efectos de la radiación , Hierro/uso terapéutico , Nanopartículas del Metal/química , Nanopartículas del Metal/efectos de la radiación , Ratones Endogámicos BALB C , Fotoquimioterapia , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/efectos de la radiación , Especies Reactivas de Oxígeno/metabolismo , Neoplasias de la Mama Triple Negativas/diagnóstico por imagen , Iterbio/química , Iterbio/efectos de la radiación , Iterbio/uso terapéutico , Itrio/química , Itrio/efectos de la radiación , Itrio/uso terapéuticoRESUMEN
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
Although nanoparticles based on Group 8 elements such as Fe and Ru have been developed, not much is known about Os nanoparticles. However, Os-based nanostructures might have potential in various applications including biomedical fields. Therefore, in this study, we synthesized Os-Te nanorods (OsTeNRs) by solvothermal galvanic replacement with Te nanotemplates. We explored the nanozymatic activity of the synthesized OsTeNRs and found that they exhibited superior photothermal conversion and photocatalytic activity. Along with chemotherapy (regorafenib) and immunotherapy, the nanozymatic, photothermal, and photodynamic activities of OsTeNRs were harnessed to develop a pentamodal treatment for hepatocellular carcinoma (HCC); in vitro and in vivo studies demonstrated that the pentamodal therapy could alleviate hypoxia in HCC cells by generating oxygen and reduced unintended drug accumulation in organs. Moreover, bone-marrow toxicity due to regorafenib could be reduced as the drug was released in a sustained manner. Thus, OsTeNRs can be considered as suitable nanotemplates for combinatorial cancer therapy.
Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Portadores de Fármacos/química , Neoplasias Hepáticas/tratamiento farmacológico , Nanotubos/química , Animales , Catálisis , Línea Celular Tumoral , Portadores de Fármacos/síntesis química , Portadores de Fármacos/efectos de la radiación , Masculino , Ratones Endogámicos C57BL , Nanotubos/efectos de la radiación , Osmio/química , Osmio/efectos de la radiación , Compuestos de Fenilurea/uso terapéutico , Fotoquimioterapia , Piridinas/uso terapéutico , Telurio/química , Telurio/efectos de la radiación , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Smart response hydrogel has a broad application prospect in human health real-time monitoring due to its responses to a variety of stimuli. In this study, we developed a novel smart hydrogel dressing based on conductive MXene nanosheets and a temperature-sensitive PNIPAm polymer. γ-Methacryloxypropyltrimethoxysilane (KH570) was selected to functionalize the surface of MXene further to improve the interface compatibility between MXene and PNIPAm. Our prepared K-M/PNIPAm hydrogel was found to have a strain-sensitive property, as well as a respond to NIR phase change and volume change. When applied as a strain flexible sensor, this K-M/PNIPAm hydrogel exhibited a high strain sensitivity with a gauge factor (GF) of 4.491, a broad working strain range of ≈250%, a fast response of â¼160 ms, and good cycle stability (i.e., 3000 s at 20% strain). Besides, this K-M/PNIPAm hydrogel can be used as an efficient NIR light-controlled drug release carrier to achieve on-demand drug release. This work paved the way for the application of smart response hydrogel in human health real-time monitoring and NIR-controlled drug release functions.
Asunto(s)
Portadores de Fármacos/química , Hidrogeles/química , Materiales Inteligentes/química , Resinas Acrílicas/química , Resinas Acrílicas/farmacología , Resinas Acrílicas/efectos de la radiación , Resinas Acrílicas/toxicidad , Animales , Línea Celular , Portadores de Fármacos/farmacología , Portadores de Fármacos/efectos de la radiación , Portadores de Fármacos/toxicidad , Liberación de Fármacos/efectos de la radiación , Elasticidad , Hidrogeles/farmacología , Hidrogeles/efectos de la radiación , Hidrogeles/toxicidad , Rayos Infrarrojos , Masculino , Metacrilatos/química , Metacrilatos/farmacología , Metacrilatos/efectos de la radiación , Metacrilatos/toxicidad , Ratones , Ratas Sprague-Dawley , Silanos/química , Silanos/farmacología , Silanos/efectos de la radiación , Silanos/toxicidad , Piel/efectos de los fármacos , Materiales Inteligentes/farmacología , Materiales Inteligentes/efectos de la radiación , Materiales Inteligentes/toxicidad , Estrés Mecánico , Tetraciclina/química , Titanio/química , Titanio/farmacología , Titanio/efectos de la radiación , Titanio/toxicidad , Cicatrización de Heridas/efectos de los fármacosRESUMEN
We demonstrate a novel structure based on smart carbon nanocomposites intended for fabricating laser-triggered drug delivery devices (DDDs). The performance of the devices relies on nanocomposites' photothermal effects that are based on polydimethylsiloxane (PDMS) with carbon nanoparticles (CNPs). Upon evaluating the main features of the nanocomposites through physicochemical and photomechanical characterizations, we identified the main photomechanical features to be considered for selecting a nanocomposite for the DDDs. The capabilities of the PDMS/CNPs prototypes for drug delivery were tested using rhodamine-B (Rh-B) as a marker solution, allowing for visualizing and quantifying the release of the marker contained within the device. Our results showed that the DDDs readily expel the Rh-B from the reservoir upon laser irradiation and the amount of released Rh-B depends on the exposure time. Additionally, we identified two main Rh-B release mechanisms, the first one is based on the device elastic deformation and the second one is based on bubble generation and its expansion into the device. Both mechanisms were further elucidated through numerical simulations and compared with the experimental results. These promising results demonstrate that an inexpensive nanocomposite such as PDMS/CNPs can serve as a foundation for novel DDDs with spatial and temporal release control through laser irradiation.
Asunto(s)
Portadores de Fármacos/química , Nanocompuestos/química , Materiales Inteligentes/química , Carbono/química , Dimetilpolisiloxanos/química , Portadores de Fármacos/efectos de la radiación , Elasticidad , Rayos Láser , Luz , Fenómenos Mecánicos , Nanocompuestos/efectos de la radiación , Rodaminas/química , Materiales Inteligentes/efectos de la radiaciónRESUMEN
The development of modern agriculture has prompted the greater input of herbicides, insecticides, and fertilizers. However, precision release and targeted delivery of these agrochemicals still remain a challenge. Here, a pesticide-fertilizer all-in-one combination (PFAC) strategy and deep learning are employed to form a system for controlled and targeted delivery of agrochemicals. This system mainly consists of three components: (1) hollow mesoporous silica (HMS), to encapsulate herbicides and phase-change material; (2) polydopamine (PDA) coating, to provide a photothermal effect; and (3) a zeolitic imidazolate framework (ZIF8), to provide micronutrient Zn2+ and encapsulate insecticides. Results show that the PFAC at concentration of 5 mg mL-1 reaches the phase transition temperature of 1-tetradecanol (37.5 °C) after 5 min of near-infrared (NIR) irradiation (800 nm, 0.5 W cm-2). The data of corn and weed are collected and relayed to deep learning algorithms for model building to realize object detection and further targeted weeding. In-field treatment results indicated that the growth of chicory herb was significantly inhibited when treated with the PFAC compared with the blank group after 24 h under NIR irradiation for 2 h. This system combines agrochemical innovation and artificial intelligence technology, achieves synergistic effects of weeding and insecticide and nutrient supply, and will potentially achieve precision and sustainable agriculture.
Asunto(s)
Portadores de Fármacos/química , Fertilizantes , Herbicidas/química , Insecticidas/química , Nanopartículas/química , Ácido 2,4-Diclorofenoxiacético/química , Ácido 2,4-Diclorofenoxiacético/toxicidad , Animales , Cichorium intybus/efectos de los fármacos , Aprendizaje Profundo , Portadores de Fármacos/efectos de la radiación , Liberación de Fármacos , Alcoholes Grasos/química , Alcoholes Grasos/efectos de la radiación , Guanidinas/química , Guanidinas/toxicidad , Herbicidas/toxicidad , Indoles/química , Indoles/efectos de la radiación , Rayos Infrarrojos , Insectos/efectos de los fármacos , Insecticidas/toxicidad , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/efectos de la radiación , Nanopartículas/efectos de la radiación , Neonicotinoides/química , Neonicotinoides/toxicidad , Nitrocompuestos/química , Nitrocompuestos/toxicidad , Polímeros/química , Polímeros/efectos de la radiaciónRESUMEN
Despite its success against cancer, photothermal therapy (PTT) (>50 °C) suffers from several limitations such as triggering inflammation and facilitating immune escape and metastasis and also damage to the surrounding normal cells. Mild-temperature PTT has been proposed to override these shortcomings. We developed a nanosystem using HepG2 cancer cell membrane-cloaked zinc glutamate-modified Prussian blue nanoparticles with triphenylphosphine-conjugated lonidamine (HmPGTL NPs). This innovative approach achieved an efficient mild-temperature PTT effect by downregulating the production of intracellular ATP. This disrupts a section of heat shock proteins that cushion cancer cells against heat. The physicochemical properties, anti-tumor efficacy, and mechanisms of HmPGTL NPs both in vitro and in vivo were investigated. Moreover, the nanoparticles cloaked with the HepG2 cell membrane substantially prolonged the circulation time in vivo. Overall, the designed nanocomposites enhance the efficacy of mild-temperature PTT by disrupting the production of ATP in cancer cells. Thus, we anticipate that the mild-temperature PTT nanosystem will certainly present its enormous potential in various biomedical applications.
Asunto(s)
Antineoplásicos/uso terapéutico , Membrana Celular/química , Ferrocianuros/química , Mitocondrias/efectos de los fármacos , Nanopartículas/química , Neoplasias/tratamiento farmacológico , Animales , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Portadores de Fármacos/química , Portadores de Fármacos/efectos de la radiación , Portadores de Fármacos/toxicidad , Liberación de Fármacos , Femenino , Ferrocianuros/efectos de la radiación , Ferrocianuros/toxicidad , Células Hep G2 , Humanos , Indazoles/química , Indazoles/uso terapéutico , Rayos Infrarrojos , Ratones Desnudos , Nanocompuestos/química , Nanocompuestos/toxicidad , Nanopartículas/efectos de la radiación , Nanopartículas/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
Escorting therapeutics for malignancies by nano-encapsulation to ameliorate treatment effects and mitigate side effects has been pursued in precision medicine. However, the majority of drug delivery systems suffer from uncontrollable drug release kinetics and thus lead to unsatisfactory triggered-release efficiency along with severe side effects. Herein, we developed a unique nanovesicle delivery system that shows near-infrared (NIR) light-triggered drug release behavior and minimal premature drug release. By co-encapsulation of superparamagnetic iron oxide (SPIO) nanoparticles, the ultrasound contrast agent perfluorohexane (PFH), and cisplatin in a silicate-polyaniline vesicle, we achieved the controllable release of cisplatin in a thermal-responsive manner. Specifically, vaporization of PFH triggered by the heat generated from NIR irradiation imparts high inner vesicle pressure on the nanovesicles, leading to pressure-induced nanovesicle collapse and subsequent cisplatin release. Moreover, the multimodal imaging capability can track tumor engagement of the nanovesicles and assess their therapeutic effects. Due to its precise inherent NIR-triggered drug release, our system shows excellent tumor eradication efficacy and biocompatibility in vivo, empowering it with great prospects for future clinical translation.
Asunto(s)
Antineoplásicos/uso terapéutico , Cisplatino/uso terapéutico , Medios de Contraste/química , Portadores de Fármacos/química , Fluorocarburos/química , Neoplasias/tratamiento farmacológico , Células A549 , Compuestos de Anilina/química , Compuestos de Anilina/efectos de la radiación , Compuestos de Anilina/toxicidad , Animales , Antineoplásicos/química , Antineoplásicos/toxicidad , Cisplatino/química , Cisplatino/toxicidad , Medios de Contraste/toxicidad , Portadores de Fármacos/efectos de la radiación , Portadores de Fármacos/toxicidad , Liberación de Fármacos , Quimioterapia , Fluorocarburos/toxicidad , Humanos , Rayos Infrarrojos , Nanopartículas Magnéticas de Óxido de Hierro/química , Nanopartículas Magnéticas de Óxido de Hierro/efectos de la radiación , Nanopartículas Magnéticas de Óxido de Hierro/toxicidad , Ratones Desnudos , Terapia Fototérmica , Silicatos/química , Silicatos/toxicidad , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Photo-chemotherapy (PCT) reveals great potential in hepatocellular carcinoma (HCC) treatment, therefore the construct of smart PCT nano-agents with high photothermal conversion efficiency and accurate drug delivery is of great significant. Herein, a novel hybrid nanomaterial MGO-TCA-FA has been designed and constructed by grafting the triformyl cholic acid (TCA) and folic acid (FA) on the surface of Fe3O4 modified graphene oxide (MGO). The doxorubicin hydrochloride (DOX) as a model drug could be effectively loaded on the MGO-TCA-FA via hydrogen bonding and π-π stacking (the drug loading amount was 1040 mg/g). The formed MGO-TCA-FA@DOX has been developed to be an effective PCT nanoplatform with the advantages of multiple-targeted drug delivery, near-infrared light (NIR) and pH triggered drug release, and photothermal conversion efficiency. In vitro experiments showed that compared with other cancer cells and normal liver cells, MGO-TCA-FA@DOX could specifically target liver cancer cells and presented significant killing ability to liver cancer cells. More importantly, in vivo experiments indicated that PCT synergistic therapy (MGO-TCA-FA@DOX) revealed the best tumor inhibition (the tumor inhibition rate was about 85%) compared with chemotherapy and photothermal therapy alone. Thus, this study supplied a viable multiple-targeted PCT nano-agent for chemo-photothermal combination therapy of liver cancer.
Asunto(s)
Antineoplásicos/uso terapéutico , Portadores de Fármacos/uso terapéutico , Grafito/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Nanocompuestos/uso terapéutico , Animales , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/efectos de la radiación , Línea Celular Tumoral , Ácidos Cólicos/química , Terapia Combinada/métodos , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/uso terapéutico , Portadores de Fármacos/química , Portadores de Fármacos/efectos de la radiación , Liberación de Fármacos , Quimioterapia , Óxido Ferrosoférrico/química , Ácido Fólico/química , Grafito/química , Grafito/efectos de la radiación , Humanos , Rayos Infrarrojos , Fenómenos Magnéticos , Ratones Endogámicos BALB C , Nanocompuestos/química , Nanocompuestos/efectos de la radiación , Terapia FototérmicaRESUMEN
Herein, we demonstrate a novel UV-induced decomposable nanocapsule of natural polysaccharide (HA-azo/PDADMAC). The nanocapsules are fabricated based on layer-by-layer co-assembly of anionic azobenzene functionalized hyaluronic acid (HA-azo) and cationic poly diallyl dimethylammonium chloride (PDADMAC). When the nanocapsules are exposed to 365 nm light, ultraviolet photons can trigger the photo-isomerization of azobenzene groups in the framework. The nanocapsules could decompose from large-sized nanocapsules to small fragments. Due to their optimized original size (~180 nm), the nanocapsules can effectively avoid biological barriers, provide a long blood circulation and achieve high tumor accumulation. It can fast eliminate nanocapsules from tumor and release the loaded drugs for chemotherapy after UV-induced dissociation. Besides, HA is an endogenous polysaccharide that shows intrinsic targetability to CD44 receptors on surface of cancer cells. The intracellular experiment shows that the HA-azo/PDADMAC nanocapsules with CD44 targeting ability and UV-controlled intracellular drug release are promising for cancer chemotherapy.
Asunto(s)
Compuestos Azo/química , Portadores de Fármacos/química , Ácido Hialurónico/química , Nanocápsulas/química , Antineoplásicos/química , Compuestos Azo/metabolismo , Compuestos Azo/efectos de la radiación , Compuestos Azo/toxicidad , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/química , Portadores de Fármacos/metabolismo , Portadores de Fármacos/efectos de la radiación , Portadores de Fármacos/toxicidad , Liberación de Fármacos/efectos de la radiación , Endocitosis/fisiología , Células Hep G2 , Humanos , Receptores de Hialuranos/metabolismo , Ácido Hialurónico/síntesis química , Ácido Hialurónico/metabolismo , Ácido Hialurónico/toxicidad , Nanocápsulas/efectos de la radiación , Nanocápsulas/toxicidad , Nanopartículas/química , Nanopartículas/metabolismo , Nanopartículas/toxicidad , Polietilenos/química , Polietilenos/toxicidad , Compuestos de Amonio Cuaternario/química , Compuestos de Amonio Cuaternario/toxicidad , Dióxido de Silicio/síntesis química , Dióxido de Silicio/química , Dióxido de Silicio/toxicidad , Estereoisomerismo , Rayos UltravioletaRESUMEN
In this study, a novel class of multifunctional responsive nanoparticles is designed and fabricated as drug nanocarriers for synergetic chemo-photothermal therapy of tumors. The proposed nanoparticles are composed of a thermo-/pH-responsive poly(N-isopropylacrylamide-co-acrylic acid) (PNA) nanogel core, a polydopamine (PDA) layer for photothermal conversion, and an outer folic acid (FA) layer as a targeting agent for the folate receptors on tumor cells. The fabricated nanoparticles show good biocompatibility and outstanding photothermal conversion efficiency. The proposed nanoparticles loaded with doxorubicin (DOX) drug molecules are stable under physiological conditions with low leakage of drugs, while rapidly release drugs in environments with low pH conditions and at high temperature. The experimental results show that the drug release process is mainly governed by Fickian diffusion. In vitro cell experimental results demonstrate that the PNA-DOX@PDA-FA nanoparticles can be phagocytized by 4T1 tumor cells and release drugs in tumor cell acidic environments, and confirm that the combined chemo and photothermal therapeutic efficacy of PNA-DOX@PDA-FA nanoparticles is higher than the photothermal therapeutic efficacy or the chemotherapeutic efficacy alone. The proposed multifunctional responsive nanoparticles in this study provide a novel class of drug nanocarriers as a promising tool for synergetic chemo-photothermal therapy of tumors.
Asunto(s)
Antineoplásicos/farmacología , Doxorrubicina/farmacología , Portadores de Fármacos/química , Nanopartículas Multifuncionales/química , Acrilamidas/química , Acrilamidas/metabolismo , Animales , Antineoplásicos/química , Línea Celular Tumoral , Doxorrubicina/química , Portadores de Fármacos/metabolismo , Portadores de Fármacos/efectos de la radiación , Liberación de Fármacos , Endocitosis/fisiología , Ácido Fólico/análogos & derivados , Ácido Fólico/metabolismo , Humanos , Concentración de Iones de Hidrógeno , Indoles/química , Indoles/metabolismo , Indoles/efectos de la radiación , Rayos Infrarrojos , Ratones , Nanopartículas Multifuncionales/metabolismo , Terapia Fototérmica , Polímeros/química , Polímeros/metabolismo , Polímeros/efectos de la radiación , TemperaturaRESUMEN
Gemcitabine and nab-paclitaxel (Abraxane®) is a standard of care chemotherapy combination used in the treatment of patients with advanced pancreatic cancer. While the combination has shown a survival benefit when compared to gemcitabine monotherapy, it is associated with significant off-target toxicity. Ultrasound targeted microbubble destruction (UTMD) has emerged as an effective strategy for the site-specific deposition of drug-payloads. However, loading a single microbubble formulation with two drug payloads can be challenging and often involves several manipulations post-microbubble preparation that can be cumbersome and generally results in low / inconsistent drug loadings. In this manuscript, we report the one-pot synthesis of a gemcitabine functionalised phospholipid and use it to successfully generate stable microbubble formulations loaded with gemcitabine (Lipid-Gem MB) or a combination of gemcitabine and paclitaxel (Lipid-Gem-PTX MB). Efficacy of the Lipid-Gem MB and Lipid-Gem-PTX MB formulations, following ultrasound (US) stimulation, was evaluated in a three-dimensional (3D) PANC-1 spheroid model of pancreatic cancer and a mouse model bearing ectopic BxPC-3 tumours. The results demonstrated a significant reduction in the cell viability in spheroids for both formulations reducing from 90 ± 10% to 62 ± 5% for Lipid-Gem MB and 84 ± 10% to 30 ± 6% Lipid-Gem-PTX MB following US irradiation. When compared with a clinically relevant dose of free gemcitabine and paclitaxel (i.e. non-particle bound) in a BxPC-3 murine pancreatic tumour model, both formulations also improved tumour growth delay with tumours 40 ± 20% and 40 ± 30% smaller than the respective free drug formulation when treated with Lipid-Gem MB and Lipid-Gem-PTX MB respectively, at the conclusion of the experiment. These results highlight the potential of UTMD mediated Gem / PTX as a treatment for pancreatic cancer and the facile preparation of Lipid-Gem-PTX MBs using a gemcitabine functionalised lipid should expedite clinical translation of this technology.
Asunto(s)
Albúminas/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Desoxicitidina/análogos & derivados , Portadores de Fármacos/efectos de la radiación , Paclitaxel/administración & dosificación , Neoplasias Pancreáticas/tratamiento farmacológico , Albúminas/farmacocinética , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Línea Celular Tumoral , Desoxicitidina/administración & dosificación , Desoxicitidina/farmacocinética , Portadores de Fármacos/química , Composición de Medicamentos/métodos , Liberación de Fármacos/efectos de la radiación , Femenino , Humanos , Masculino , Ratones , Microburbujas , Nanopartículas/química , Nanopartículas/efectos de la radiación , Paclitaxel/farmacocinética , Neoplasias Pancreáticas/patología , Fosfolípidos/química , Ondas Ultrasónicas , Ensayos Antitumor por Modelo de Xenoinjerto , GemcitabinaRESUMEN
Hydrogels often have poor mechanical properties which limit their application in load-bearing tissues such as muscle and cartilage. In this work, a near-infrared light-triggered stretchable thermal-sensitive hydrogel with ultra-high drug loading was developed by a combination of natural polymeric nanocrystals, a network of synthetic thermo-responsive polymer, and magnetic Fe3O4 nanoparticles. The hydrogels comprise cellulose nanocrystals (CNCs) decorated with Fe3O4 nanoparticles (Fe3O4/CNCs) dispersed homogeneously in poly(N-isopropylacrylamide) (PNIPAm) networks. The composite hydrogels exhibit an extensibility of 2200%. Drug loading of vancomycin (VCM) reached a high value of 10.18 g g-1 due to the dispersion of Fe3O4/CNCs and the interactions between the CNCs and the PNIPAm network. Importantly, the hydrogels demonstrated a thermo-response triggered by NIR, with the temperature increasing from 26 to 41 °C within 60 s. The hydrogels have high biocompatibility evidenced by cell proliferation tests, illustrating that these hydrogels are promising as dressings for wound closure, and wound healing.
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Celulosa/química , Portadores de Fármacos/química , Hidrogeles/química , Nanopartículas de Magnetita/química , Resinas Acrílicas/química , Resinas Acrílicas/efectos de la radiación , Resinas Acrílicas/toxicidad , Celulosa/efectos de la radiación , Celulosa/toxicidad , Portadores de Fármacos/efectos de la radiación , Portadores de Fármacos/toxicidad , Liberación de Fármacos , Células HEK293 , Humanos , Hidrogeles/efectos de la radiación , Hidrogeles/toxicidad , Rayos Infrarrojos , Nanopartículas de Magnetita/efectos de la radiación , Nanopartículas de Magnetita/toxicidad , Nanocompuestos/química , Nanocompuestos/efectos de la radiación , Nanocompuestos/toxicidad , Porosidad , Temperatura , Vancomicina/químicaRESUMEN
There has been growing interest in the application of gold nanorods (GNRs) to tumor therapy due to the unique properties they possess. In the past, GNRs were not used in clinical treatments as they lacked stability in vivo and were characterized by potential toxicity. Despite these issues, the significant potential for utilizing GNRs to conduct safe and effective treatments for tumors cannot be ignored. Therefore, it remains crucial to thoroughly investigate the mechanisms behind the toxicity of GNRs in order to provide the means of overcoming obstacles to its full application in the future. This review presents the toxic effects of GNRs, the factors affecting toxicity and the methods to improve biocompatibility, all of which are presently being studied. Finally, we conclude by briefly discussing the current research status of GNRs and provide additional perspective on the challenges involved along with the course of development for GNRs in the future.
Asunto(s)
Antineoplásicos/uso terapéutico , Nanopartículas del Metal/uso terapéutico , Nanotubos/química , Neoplasias/tratamiento farmacológico , Animales , Antineoplásicos/química , Antineoplásicos/efectos de la radiación , Línea Celular Tumoral , Doxorrubicina/uso terapéutico , Portadores de Fármacos/química , Portadores de Fármacos/efectos de la radiación , Portadores de Fármacos/uso terapéutico , Quimioterapia , Oro/química , Oro/efectos de la radiación , Humanos , Nanopartículas del Metal/química , Nanopartículas del Metal/efectos de la radiación , Nanotubos/efectos de la radiación , Fotoquimioterapia , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/efectos de la radiación , Fármacos Fotosensibilizantes/uso terapéutico , Terapia FototérmicaRESUMEN
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
Herein, we describe capsule polymer particles with precisely controlled pH-responsive release properties prepared directly via the interfacial photo-cross-linking of spherical poly(2-diethylaminoethyl methacrylate-co-2-cinnamoylethyl methacrylate) (P(DEAEMA-CEMA)) particles. In the interfacial photo-cross-linking, photoreactive cinnamoyl groups in the polymer particles were cross-linked via [2π + 2π] cycloaddition reactions at the polymer/water interface, showing that the shell-cross-linked hollow polymer particles can be directly prepared from spherical polymer particles. The approach has fascinating advantages such as using minimal components, simplicity, and not requiring sacrificial template particles and toxic solvents. The following important observations are made: (I) encapsulated materials were stably retained in the capsule particles under neutral pH conditions; (II) encapsulated materials were released from the capsule particles under acidic pH conditions; (III) the release kinetics of encapsulated materials were controlled by the pH conditions; i.e., immediate and sustained release was achieved by varying the acidity of the aqueous media; (IV) the photoirradiation time did not significantly affect the release kinetics under different pH conditions; and (V) the pH-responsive release properties were regulated by changing the polymer composition in P(DEAEMA-CEMA). Furthermore, by exploiting the pH-responsiveness, capsule particles are successfully obtained via an all-aqueous process from spherical polymer particles. The advantages of the all-aqueous encapsulation process allowed the water-soluble biomacromolecules such as DNA and saccharides to be successfully encapsulated in the P(DEAEMA-CEMA) hollow particles. With this simple interfacial photo-cross-linking strategy, we envision the ready synthesis of sophisticated particulate materials for broad application in advanced research fields.