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1.
Biosens Bioelectron ; 264: 116668, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39173340

RESUMEN

Traditional hepatocellular carcinoma-chip models lack the cell structure and microenvironments necessary for high pathophysiological correlation, leading to low accuracy in predicting drug efficacy and high production costs. This study proposed a decellularized hepatocellular carcinoma-on-a-chip model to screen anti-tumor nanomedicine. In this model, human hepatocellular carcinoma (HepG2) and human normal liver cells (L02) were co-cultured on a three-dimensional (3D) decellularized extracellular matrix (dECM) in vitro to mimic the tumor microenvironments of human hepatocellular carcinoma in vivo. Additionally, a smart nanomedicine was developed by encapsulating doxorubicin (DOX) into the ferric oxide (Fe3O4)-incorporated liposome nanovesicle (NLV/Fe+DOX). NLV/Fe+DOX selectively killed 78.59% ± 6.78% of HepG2 cells through targeted delivery and synergistic chemo-chemodynamic-photothermal therapies, while the viability of surrounding L02 cells on the chip model retained high, at over 90.0%. The drug efficacy tested using this unique chip model correlated well with the results of cellular and animal experiments. In summary, our proposed hepatocellular carcinoma-chip model is a low-cost yet accurate drug-testing platform with significant potential for drug screening.


Asunto(s)
Carcinoma Hepatocelular , Doxorrubicina , Dispositivos Laboratorio en un Chip , Neoplasias Hepáticas , Nanomedicina , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Doxorrubicina/farmacología , Doxorrubicina/química , Doxorrubicina/uso terapéutico , Células Hep G2 , Nanomedicina/métodos , Animales , Liposomas/química , Matriz Extracelular/química , Matriz Extracelular/efectos de los fármacos , Compuestos Férricos/química , Técnicas Biosensibles/métodos , Microambiente Tumoral/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/uso terapéutico
2.
Biomed Mater ; 19(2)2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38266273

RESUMEN

The rapid, irreversible change of active Fe2+to inactive Fe3+after the Fenton reaction occurring reduces the chemodynamic therapeutic (CDT) effect. Therefore, manipulation of the tumor microenvironment to provide sufficient hydrogen peroxide (H2O2) while maintaining metal ion catalyst activity is critical for effective CDT. Here,ß-Lapachone (LPC) was loaded by mesoporous silica nanoparticles (MSNs) and coated with polydopamine (PDA) to further chelate Fe3+and link aptamer AS1411, and a pH-controlled released, chemotherapy-photothermal therapy (PTT)-enhanced CDT-small molecule therapy combination drug delivery system with passive and active tumor targeting was engineered (designated asß-LPC@MSN@PDA/Fe3+-AS1411, LMPFA). The results showed that LFMPA nanoparticles massively accumulated in tumor tissues to achieve tumor targeting through AS1411 mediating and enhanced permeability and retention (EPR) effect. Subsequently, PDA released Fe3+and LPC through acid response to exhibited CDT and chemotherapeutic therapy. Meanwhile, the photothermal effect of PDA promoted the release of LPC from the pores of MSN. LPC exerted chemotherapy effect and cyclically producing of H2O2by the catalysis of NQO1, which enhanced the CDT activated by Fe3+. In addition, while serving as a targeted ligand, AS1411 could also exhibit a small molecule therapeutic effect by binding to nucleoli of tumor cells. This unique nano delivery system achieved the combination of chemotherapy, PTT, enhanced CDT and small molecule therapy, and fought against malignant tumors synergistically through multi-target and multi-dimension.


Asunto(s)
Nanopartículas , Naftoquinonas , Neoplasias , Humanos , Peróxido de Hidrógeno , Sistemas de Liberación de Medicamentos , Línea Celular Tumoral , Microambiente Tumoral
3.
Front Bioeng Biotechnol ; 11: 1139426, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37101748

RESUMEN

Introduction: The application of titanium dioxide nanoparticles (TiO2 NPs) for cancer therapy has been studied for decades; however, the targeted delivery of TiO2 NPs to tumor tissues is challenging, and its efficiency needs to be improved. Method: In this study, we designed an oxygen-deficient TiO2-x coated with glutamine layer for targeted delivery, as well as the enhanced separation of electrons (e-) and holes (h+) following the joint application of sonodynamic therapy (SDT) and photothermal therapy (PTT). Results: This oxygen-deficient TiO2-x possesses relatively high photothermal and sonodynamic efficiency at the 1064 nm NIR-II bio-window. The GL-dependent design eased the penetration of the TiO2-x into the tumor tissues (approximately three-fold). The in vitro and in vivo tests showed that the SDT/PTT-based synergistic treatment achieved more optimized therapeutic effects than the sole use of either SDT or PTT. Conclusion: Our study provided a safety targeted delivery strategy, and enhanced the therapeutic efficiency of SDT/PTT synergistic treatment.

4.
Mater Today Bio ; 17: 100478, 2022 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-36388463

RESUMEN

Tumor microenvironment (TME)-activated theranostics is a promising strategy to effectively identify small lesions, improve antitumor efficacy, and reduce the risk of undesired side effects. Hypoxia, as a common characteristic of TME, can serve as a preferred site for stimulus-dependent activation; however, tumor-hypoxia levels in various developmental stages exhibit different characteristics, severely limiting the response sensitivity. Herein, a circulating self-reinforcing hypoxic nanoamplifier (CGH NAs) is developed that utilizes a dual-chain reaction process (internal regulation, internal regulation) to achieve precise activation of NIR-II FL/photoacoustic (PA) imaging-guided synergistic therapy. Inspired by the positive correlation of nitroreductase (NTR) with hypoxia, the CGH NAs encapsulate CQ4T and GOx into NTR-sensitive hyaluronic acid-nitroimidazole (HA-NI) shell via a self-assembly approach, enabling aggregation-caused NIR-II FL quenching and tumor-accurate delivery. When CGH NAs efficiently accumulated in the tumor region, the intensive local NTR reduced hydrophobic -NO2 to hydrophilic -NH2, which lead to disassembly of CGH NAs. The released GOx could consume O2 (internal regulation) and glucose to cut off the energy supply, inducing tumor-starvation therapy; generate gluconic acid and H2O2 (oxidative stress). Meanwhile, the released CQ4T promoted rapid recovery of NIR-II FL signals for imaging-guided PDT, which could simultaneously deplete intratumoral O2 (external stimulation). Remarkably, the strengthened tumor-hypoxia levels in turn accelerated the NTR-responsive degradation of the CGH NAs, thereby achieving high-efficiency theranostic.

5.
Adv Healthc Mater ; 11(19): e2200776, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35912918

RESUMEN

Immunotherapy efficacy has been limited by tumor-associated macrophages (TAMs), which are the most abundant immune regulatory cells infiltrating around tumor tissues. The repolarization of pro-tumor M2 TAMs to anti-tumor M1 TAMs is a very promising immunotherapeutic strategy for cancer therapy. In this manuscript, multifunctional 2D iron-based nanosheets (FeNSs) are synthesized via a simple hydrothermal method for the first time, which not only possess photothermal and photodynamic properties, but also can repolarize TAMs from M2 to M1. After modifying with polyethylene glycol and loading with bioreductive prodrug banoxantrone (AQ4N), abbreviated as AP FeNSs, it can effectively repolarize TAMs from M2 to M1 and deliver AQ4N to tumor microenvironment (TME). Moreover, the repolarized M1 TAMs overexpress inducible nitric oxide synthase, which can convert nontoxic AQ4N to cytotoxic AQ4 under hypoxic TME, enabling immunomodulation-activated chemotherapy. A series of in vitro and in vivo results corroborate that AP FeNSs effectively exert photothermal and photodynamic effects and repolarize M2 TAMs to M1 TAMs, releasing inflammatory factors and activating the chemotherapeutic effect, thereby realizing synergistic tumor therapy.


Asunto(s)
Neoplasias , Profármacos , Antraquinonas , Humanos , Factores Inmunológicos/farmacología , Inmunoterapia/métodos , Hierro/farmacología , Macrófagos , Neoplasias/tratamiento farmacológico , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxido Nítrico Sintasa de Tipo II/farmacología , Fototerapia , Polietilenglicoles/farmacología , Profármacos/farmacología , Microambiente Tumoral
6.
Theranostics ; 12(4): 1800-1815, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35198074

RESUMEN

Rationale: With the advantages of tumor-targeting, pH-responsive drug releasing, and biocompatibility, ferritin nanocage emerges as a promising drug carrier. However, its wide applications were significantly hindered by the low loading efficiency of hydrophobic drugs. Herein, we redesigned the inner surface of ferritin drug carrier (ins-FDC) by fusing the C- terminus of human H ferritin (HFn) subunit with optimized hydrophobic peptides. Methods: Hydrophobic and hydrophilic drugs were encapsulated into the ins-FDC through the urea-dependent disassembly/reassembly strategy and the natural drug entry channel of the protein nanocage. The morphology and drug loading/releasing abilities of the drug-loaded nanocarrier were then examined. Its tumor targeting character, system toxicity, application in synergistic therapy, and anti-tumor action were further investigated. Results: After optimization, 39 hydrophobic Camptothecin and 150 hydrophilic Epirubicin were encapsulated onto one ins-FDC nanocage. The ins-FDC nanocage exhibited programed drug release pattern and increased the stability and biocompatibility of the loaded drugs. Furthermore, the ins-FDC possesses tumor targeting property due to the intrinsic CD71-binding ability of HFn. The loaded drugs may penetrate the brain blood barrier and accumulate in tumors in vivo more efficiently. As a result, the drugs loaded on ins-FDC showed reduced side effects and significantly enhanced efficacy against glioma, metastatic liver cancer, and chemo-resistant breast tumors. Conclusions: The ins-FDC nanocarrier offers a promising novel means for the delivery of hydrophobic compounds in cancer treatments, especially for the combination therapies that use both hydrophobic and hydrophilic chemotherapeutics.


Asunto(s)
Ferritinas , Glioma , Apoferritinas/uso terapéutico , Línea Celular Tumoral , Doxorrubicina/uso terapéutico , Portadores de Fármacos/uso terapéutico , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Epirrubicina , Ferritinas/química , Glioma/tratamiento farmacológico , Humanos
7.
Small ; 17(47): e2103919, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34623753

RESUMEN

Given that traditional anticancer therapies fail to significantly improve the prognoses of triple negative breast cancer (TNBC), new modalities with high efficiency are urgently needed. Herein, by mixing the metal-phenolic network formed by tannic acid (TA), bleomycin (BLM), and Fe3+ with glutathione peroxidase 4 (GPX4) inhibitor (ML210) loaded hollow mesoporous Prussian blue (HMPB) nanocubes, the HMPB/ML210@TA-BLM-Fe3+ (HMTBF) nanocomplex is prepared to favor the ferroptosis/apoptosis synergism in TNBC. During the intracellular degradation, Fe3+ /Fe2+ conversion mediated by TA can initiate the Fenton reaction to drastically upregulate the reactive oxygen species level in cells, subsequently induce the accumulation of lipid peroxidation, and thereby cause ferroptotic cell death; meanwhile, the released ML210 efficiently represses the activity of GPX4 to activate ferroptosis pathway. Besides, the chelation of Fe2+ with BLM leads to in situ BLM toxification at tumor site, then triggers an effective apoptosis to synergize with ferroptosis for tumor therapy. As a result, the superior in vivo antitumor efficacy of HMTBF is corroborated in a 4T1 tumor-bearing mice model regarding tumor growth suppression, indicating that the nanoformulations can serve as efficient ferroptosis and apoptosis inducers for use in combinatorial TNBC therapy.


Asunto(s)
Ferroptosis , Nanopartículas , Neoplasias de la Mama Triple Negativas , Animales , Apoptosis , Bleomicina , Línea Celular Tumoral , Ferrocianuros , Humanos , Ratones , Polifenoles , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico
8.
Carbohydr Polym ; 273: 118608, 2021 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-34561007

RESUMEN

Polycyclodextrin (denoted PCD) composed of cyclodextrin monomer units and 1,3-diethoxypropan-2-ol containing many hydroxyl groups with lone pairs of electrons, easily coordinated with transition metals with empty orbitals. The CD unit can also provide host-guest binding sites for functional molecules. This article utilizes this feature of PCD for the first time as a "linker" to combine transition metal nanomaterials with synergistic functional molecules. We synthesized PCD with 50% CD monomer by epichlorohydrin cross-linking method. Utilizing the coordination effect of the hydroxyl group in PCD and the iron ion in photothermal nanoparticles (PB-Yb), the PCD is coated on its surface; simultaneously, CD in PCD can form a host-guest complex with adamantane-modified zinc phthalocyanine (Pc) photosensitizer. Using PCD as a "linker", PB-Yb and Pc (denoted PYPP) were combined to improve the solubility of PB-Yb, reduce the aggregation degree of Pc to increase their activity, and achieve photothermal and photodynamic synergistic tumor therapy.


Asunto(s)
Antineoplásicos/uso terapéutico , Ciclodextrinas/química , Nanopartículas/química , Neoplasias/tratamiento farmacológico , Fármacos Fotosensibilizantes/uso terapéutico , Polímeros/química , Adamantano/efectos de la radiación , Adamantano/uso terapéutico , Animales , Ciclodextrinas/toxicidad , Femenino , Ferrocianuros/química , Ferrocianuros/toxicidad , Células HeLa , Humanos , Isoindoles/efectos de la radiación , Isoindoles/uso terapéutico , Luz , Ratones Endogámicos BALB C , Nanomedicina/métodos , Nanopartículas/toxicidad , Neoplasias/metabolismo , Compuestos Organometálicos/efectos de la radiación , Compuestos Organometálicos/uso terapéutico , Fármacos Fotosensibilizantes/efectos de la radiación , Polímeros/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Iterbio/química , Iterbio/toxicidad , Compuestos de Zinc/efectos de la radiación , Compuestos de Zinc/uso terapéutico
9.
Adv Sci (Weinh) ; 8(14): e2100241, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34032026

RESUMEN

The conversion of endogenous H2 O2 into toxic hydroxyl radical (• OH) via catalytic nanoparticles is explored for tumor therapy and received considerable success. The intrinsic characteristics of microenvironment in tumor cells, such as limited H2 O2 and overexpressed glutathione (GSH), hinder the intracellular • OH accumulation and thus weaken therapeutic efficacy considerably. In this study, fine CaO2 nanoparticles with Cu-ferrocene molecules at the surface (CaO2 /Cu-ferrocene) are successfully designed and synthesized. Under an acidic condition, the particles release Ca2+ ions and H2 O2 in a rapid fashion, while they can remain stable in neutral. In addition, agitated production of • OH occurs following the Fenton reaction of H2 O2 and ferrocene molecules, and GSH is consumed by Cu2+ ions to avoid the potential • OH consumption. More interestingly, in addition to the exogenous Ca2+ released by the particles, the enhanced • OH production facilitates intracellular calcium accumulation by regulating Ca2+ channels and pumps of tumor cells. It turns out that promoted • OH induction and intracellular calcium overload enable significant in vitro and in vivo antitumor phenomena.


Asunto(s)
Calcio/metabolismo , Cobre/metabolismo , Compuestos Ferrosos/metabolismo , Glutatión/metabolismo , Metalocenos/metabolismo , Nanopartículas/uso terapéutico , Neoplasias/tratamiento farmacológico , Peróxidos/metabolismo , Animales , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Glutatión/efectos de los fármacos , Ratones
10.
ACS Appl Mater Interfaces ; 13(21): 24532-24542, 2021 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-34019368

RESUMEN

Sonodynamic therapy (SDT) is a promising method for tumor treatment, but self-quenching property, low loading efficiency of sonosensitizers, and hypoxia tumor microenvironment (TME) hinder the efficiency of SDT. Herein, an erythrocyte membrane (EM)-camouflaged metal-organic framework (MOF) of PCN-224 nanoparticles (NPs) integrated with platinum (Pt) NPs as well as glucose oxidase (GOx) has been developed to overcome these limits. Porphyrin-based PCN-224 NPs are synthesized as a sonosensitizer with a large amount of well-organized porphyrin molecules while simultaneously acting as the nanocarriers (NCs) for Pt NPs and GOx. When the NCs are internalized by tumor cells, Pt NPs on their surface are able to utilize endogenous hydrogen peroxide (H2O2) to produce oxygen for the relief of tumor hypoxia, thus enhancing the SDT effect. After EM cloaking, the longer circulation time can improve biocompatibility in vivo and enhance accumulation in tumor tissue. Loaded GOx is beneficial to local glucose consumption and can realize the tumor starvation therapy effect. Consequently, these multifunctional NCs show amplified synergistic therapeutic effects of tumor SDT and starvation therapy, which can efficiently inhibit the tumor growth.


Asunto(s)
Portadores de Fármacos , Membrana Eritrocítica , Glucosa Oxidasa/metabolismo , Nanopartículas del Metal/administración & dosificación , Neoplasias/tratamiento farmacológico , Platino (Metal)/química , Hipoxia Tumoral , Terapia por Ultrasonido , Animales , Terapia Combinada , Nanopartículas del Metal/química , Ratones , Ratones Endogámicos ICR , Neoplasias/patología , Neoplasias/terapia , Ensayos Antitumor por Modelo de Xenoinjerto
11.
ACS Nano ; 15(3): 5735-5751, 2021 03 23.
Artículo en Inglés | MEDLINE | ID: mdl-33705663

RESUMEN

As next-generation artificial enzymes, nanozymes have shown great promise for tumor catalytic therapy. In particular, their peroxidase-like activity has been employed to catalyze hydrogen peroxide (H2O2) to produce highly toxic hydroxyl radicals (•OH) to kill tumor cells. However, limited by the low affinity between nanozymes with H2O2 and the low level of H2O2 in the tumor microenvironment, peroxidase nanozymes usually produced insufficient •OH to kill tumor cells for therapeutic purposes. Herein, we present a pyrite peroxidase nanozyme with ultrahigh H2O2 affinity, resulting in a 4144- and 3086-fold increase of catalytic activity compared with that of classical Fe3O4 nanozyme and natural horseradish peroxidase, respectively. We found that the pyrite nanozyme also possesses intrinsic glutathione oxidase-like activity, which catalyzes the oxidation of reduced glutathione accompanied by H2O2 generation. Thus, the dual-activity pyrite nanozyme constitutes a self-cascade platform to generate abundant •OH and deplete reduced glutathione, which induces apoptosis as well as ferroptosis of tumor cells. Consequently, it killed apoptosis-resistant tumor cells harboring KRAS mutation by inducing ferroptosis. The pyrite nanozyme also exhibited favorable tumor-specific cytotoxicity and biodegradability to ensure its biosafety. These results indicate that the high-performance pyrite nanozyme is an effective therapeutic reagent and may aid the development of nanozyme-based tumor catalytic therapy.


Asunto(s)
Ferroptosis , Peróxido de Hidrógeno , Apoptosis , Hierro , Sulfuros
12.
Adv Sci (Weinh) ; 7(17): 2001223, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32995127

RESUMEN

Glucose-oxidase (GOx)-mediated starvation by consuming intracellular glucose has aroused extensive exploration as an advanced approach for tumor treatment. However, this reaction of catalytic oxidation by GOx is highly dependent on the on-site oxygen content, and thus starvation therapy often suffers unexpected anticancer outcomes due to the intrinsic tumorous hypoxia. Herein, porous platinum nanospheres (pPts), incorporated with GOx molecules (PtGs), are synthesized to enable synergistic cancer therapy. In this system, GOx can effectively catalyze the oxidation of glucose to generate H2O2, while pPt triggers the decomposition of both endogenous and exogenous H2O2 to produce considerable content of O2 to facilitate the glucose consumption by GOx. Meanwhile, pPt induces remarkable content of intracellular reactive oxygen species (ROS) under an alternating electric field, leading to cellular oxidative stress injury and promotes apoptosis following the mechanism of electrodynamic therapy (EDT). In consequence, the PtG nanocomposite exhibits significant anticancer effect both in vitro and in vivo. This study has therefore demonstrated a fascinating therapeutic platform enabling oxygen-inductive starvation/EDT synergistic strategy for effective tumor treatment.

13.
Colloids Surf B Biointerfaces ; 192: 111005, 2020 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-32315920

RESUMEN

Localized drug delivery systems (LDDSs), in the forms of fibers or hydrogel, have emerged as an alternative approach for effective cancer treatment, but suffer challenges in the limited efficacy originated from sole therapeutic functionality. Herein, a multifunctional LDDS, showing feasibility for minimally-invasive implantation, was designed and synthesized for on-site chemo-photothermal synergistic therapy. In this system, polydopamine (PDA) nanoparticles, loaded with doxorubicin (DOX), were assembled at the surface of electrospun PCL-gelatin (PG) fibers (PG@PDA-DOX). The composite PG@PDA-DOX nanofibers could effectively transform NIR light into heat and present excellent photostability. In addition, low pH and NIR irradiation enabled remarkably accelerated DOX release. The in vitro study of PG@PDA-DOX fibers showed effective anti-cancer effect with irradiation of 808 nm NIR by inducing cell apoptosis and suppressing cell proliferation. The in vivo study, by implanting PG@PDA-DOX nanofibers in the patient derived xenograft (PDX) model via minimally-invasive surgery, presented that the composite fibers can effectively inhabit tumor growth by the combined chemo-photothermal effect without clear systematic side-effects. This study has therefore demonstrated a minimally-invasive platform, in a fibrous mesh form, with both high therapeutic efficacy and considerable potential in clinical translation for liver cancer treatment.

14.
Pharmaceutics ; 11(6)2019 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-31159476

RESUMEN

As caterpillars detect the presence of predators and secrete poison, herein, we show an innovative and highly effective cancer therapeutic system using biocompatible chitosan nanofiber (CNf) installed with a pH-responsive motif that senses tumor extracellular pH, pHe, prior to delivering dual-modal light-activatable materials for tumor reduction. The filamentous nanostructure of CNf is dynamic during cell interaction and durable in blood circulation. Due to its amine group, CNf uptakes a large amount of photothermal gold nanoparticles (AuNPs, >25 wt %) and photodynamic chlorin e6 (Ce6, >5 wt %). As the innovative CNf approaches tumors, cationic CNf effectively discharges AuNPs connected to the pH-responsive motif via electrostatic repulsion and selectively binds to tumor cells that are generally anionic, via the electrostatic attraction accompanied by CNf. We demonstrated via these actions that the endocytosed Ce6 (on CNf) and AuNPs (free from CNf) significantly elicited tumor cell death under light irradiation. As a result, the synergistic interplay of thermogenesis and photodynamic action was observed to switch on at the pHe, resulting in a striking reduction in tumor formation and growth rate upon light exposure.

15.
Theranostics ; 8(4): 1042-1058, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29463998

RESUMEN

Heavy atom nanoparticles have high X-ray absorption capacity and near infrared (NIR) photothermal conversion efficiency, which could be used as radio-sensitizers. We hypothesized that concave PtCu octopod nanoframes (OPCNs) would be an efficient nanoplatform for synergistic radio-photothermal tumor ablation. Methods: In this study, we newly exploited a folic acid-receptor (FR) mediated photothermal radiotherapy nanoagent base on OPCNs. OPCNs were synthesized with a hydrothermal method and then modified with polyethylene glycol (PEG) and folic acid (FA). A series of physical and chemical characterizations, cytotoxicity, targeting potential, endocytosis mechanism, biodistribution, systematic toxicological evaluation, pharmacokinetics, applications of OPCNs-PEG-FA for in vitro and in vivo infrared thermal imaging (ITI)/photoacoustic imaging (PAI) dual-modal imaging and synergistic photothermal radiotherapy against tumor were carried out. Results: The OPCNs-PEG-FA demonstrated good biocompatibility, strong NIR absorption and X-ray radio-sensitization, which enabling it to track and visualize tumor in vivo via ITI/PAI dual-modal imaging. Moreover, the as-synthesized OPCNs-PEG-FA exhibited remarkable photothermal therapy (PTT) and radiotherapy (RT) synergistic tumor inhibition when treated with NIR laser and X-ray. Conclusion: A novel multifunctional theranostic nanoplatform based on OPCNs was designed and developed for dual-modal image-guided synergistic tumor photothermal radiotherapy.


Asunto(s)
Diagnóstico por Imagen/métodos , Hipertermia Inducida/métodos , Nanocompuestos/administración & dosificación , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Fotoquimioterapia/métodos , Radioterapia Guiada por Imagen/métodos , Línea Celular Tumoral , Ácido Fólico/metabolismo , Humanos , Modelos Biológicos , Nanocompuestos/química , Técnicas Fotoacústicas/métodos , Nanomedicina Teranóstica/métodos , Termometría/métodos
16.
Carbohydr Polym ; 180: 112-121, 2018 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-29103486

RESUMEN

We designed an injectable hydrogel by dissolving MoS2/Bi2S3-PEG (MBP), doxorubicin (DOX) and agar into water for the concurrent tumor photothermal and chemotherapy. The formed solution was able to be intra-tumorally (I.T.) administered into tumor at a relatively high temperature and automatically formed a hydrogel after cooling to body temperature. The resultant Agar/MBP/DOX (AMD) hydrogel can act as a macro-vessel to retain the MBP nanosheet and DOX and restrict their access to body fluid circulation. Moreover, AMD hydrogel did not compromise the photoacoustic and computed tomography imaging capacity, as well as the photothermal and chemotherapy efficiency of MBP nanosheets and DOX. The heat from the photothermal transformation of MBP nanosheet can promote the drug-release from the hydrogel and thus enable an on-demand drug release. Furthermore, antibiotics were also able to be encapsulated in the hydrogel to avoid the potential wound infection during tumor surgery.


Asunto(s)
Antineoplásicos/administración & dosificación , Doxorrubicina/administración & dosificación , Portadores de Fármacos/síntesis química , Hidrogeles/síntesis química , Agar/química , Amoxicilina/administración & dosificación , Amoxicilina/farmacocinética , Animales , Antibacterianos/administración & dosificación , Antibacterianos/farmacocinética , Antineoplásicos/farmacocinética , Bismuto/química , Disulfuros/química , Doxorrubicina/farmacocinética , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/química , Liberación de Fármacos , Células HT29 , Humanos , Hidrogeles/administración & dosificación , Hidrogeles/química , Inyecciones , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Molibdeno/química , Fotoquimioterapia/métodos , Polietilenglicoles/química , Sulfuros/química
17.
Adv Mater ; 27(44): 7117-22, 2015 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-26447460

RESUMEN

MoS2 nanosheets and a doxorubicin (DOX)-containing poly (lactic-co-glycolic acid) (PLGA)/MoS2 /DOX composite implant are successfully constructed based on the unique phase-changing behavior of PLGA/MoS2 /DOX oleosol within tumors. The fast phase transformation can firmly restrict MoS2 and DOX within tumors, and the integrated MoS2 and DOX can endow the implant with high synergistic photothermal and chemotherapeutic efficiency against tumors.


Asunto(s)
Disulfuros/química , Portadores de Fármacos/química , Hipertermia Inducida/métodos , Rayos Infrarrojos , Molibdeno/química , Neoplasias/terapia , Animales , Línea Celular , Doxorrubicina/química , Doxorrubicina/uso terapéutico , Inyecciones , Ácido Láctico/química , Rayos Láser , Ratones , Modelos Moleculares , Conformación Molecular , Neoplasias/tratamiento farmacológico , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Prótesis e Implantes
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