RESUMEN
Activatable imaging probes are promising to achieve increased signal-to-noise ratio for accurate tumor diagnosis and treatment monitoring. Magnetic resonance imaging (MRI) is a noninvasive imaging technique with excellent anatomic spatial resolution and unlimited tissue penetration depth. However, most of the activatable MRI contrast agents suffer from metal ion-associated potential long-term toxicity, which may limit their bioapplications and clinical translation. Herein, an activatable MRI agent with efficient MRI performance and high safety is developed for drug (doxorubicin) loading and tumor signal amplification. The agent is based on pH-responsive polymer and gadolinium metallofullerene (GMF). This GMF-based contrast agent shows high relaxivity and low risk of gadolinium ion release. At physiological pH, both GMF and drug molecules are encapsulated into the hydrophobic core of nanoparticles formed by the pH-responsive polymer and shielded from the aqueous environment, resulting in relatively low longitudinal relativity and slow drug release. However, in acidic tumor microenvironment, the hydrophobic-to-hydrophilic conversion of the pH-responsive polymer leads to amplified MR signal and rapid drug release simultaneously. These results suggest that the prepared activatable MRI contrast agent holds great promise for tumor detection and monitoring of drug release.
Asunto(s)
Portadores de Fármacos , Fulerenos/química , Gadolinio/química , Imagen por Resonancia Magnética , Animales , Medios de Contraste/química , Preparaciones de Acción Retardada/uso terapéutico , Doxorrubicina/química , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Células HeLa , Humanos , Concentración de Iones de Hidrógeno , Ratones , Nanopartículas/química , Neoplasias/tratamiento farmacológico , Polímeros/química , Microambiente TumoralRESUMEN
The approach of concurrent-to-synchronous chemoradiation has now been advanced by well-designed nanovesicles that permit X-ray irradiation-triggered instant drug release. The nanovesicles consist of Au nanoparticles tethered with irradiation labile linoleic acid hydroperoxide (LAHP) molecules and oxidation-responsive poly(propylene sulfide)-poly(ethylene glycol) (PPS-PEG) polymers, where DOX were loaded in the inner core of the vesicles (Au-LAHP-vDOX). Upon irradiation, the inâ situ formation of hydroxyl radicals from LAHP molecules triggers the internal oxidation of PPS from being hydrophobic to hydrophilic, leading to degradation of the vesicles and burst release of cargo drugs. In this manner, synchronous chemoradiation showed impressive anticancer efficacy both in vitro and in a subcutaneous mouse tumor model by one-dose injection and one-time irradiation.
Asunto(s)
Antibióticos Antineoplásicos/administración & dosificación , Portadores de Fármacos/química , Portadores de Fármacos/efectos de la radiación , Liberación de Fármacos/efectos de la radiación , Oro/química , Nanopartículas/química , Rayos X , Animales , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/administración & dosificación , Doxorrubicina/química , Doxorrubicina/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Ácidos Linoleicos/química , Peróxidos Lipídicos/química , Ratones , Neoplasias Experimentales/diagnóstico por imagen , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/patología , Tamaño de la Partícula , Polímeros/química , Tomografía de Emisión de Positrones , Propiedades de SuperficieRESUMEN
Polymeric micelle-based drug delivery systems have dramatically improved the delivery of small molecular drugs, yet multiple challenges remain to be overcome. A polymeric nanomedicine has now been engineered that possesses an ultrahigh loading (59 %) of a glutathione (GSH)-sensitive heterodimeric multifunctional prodrug (HDMP) to effectively co-deliver two synergistic drugs to tumors. An HDMP comprising of chemotherapeutic camptothecin (CPT) and photosensitizer 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-α (HPPH) was conjugated via a GSH-cleavable linkage. The intrinsic fluorogenicity and label-free radio-chelation (64 Cu) of HPPH enabled direct drug monitoring by fluorescence imaging and positron emission tomography (PET). Through quantitative PET imaging, HDMP significantly improves drug delivery to tumors. The high synergistic therapeutic efficacy of HDMP-loaded NPs highlights the rational design of HDMP, and presents exciting opportunities for polymer NP-based drug delivery.
Asunto(s)
Antineoplásicos/administración & dosificación , Camptotecina/administración & dosificación , Preparaciones de Acción Retardada/metabolismo , Glutatión/metabolismo , Fármacos Fotosensibilizantes/administración & dosificación , Profármacos/administración & dosificación , Animales , Antineoplásicos/uso terapéutico , Camptotecina/uso terapéutico , Línea Celular Tumoral , Preparaciones de Acción Retardada/química , Monitoreo de Drogas , Sinergismo Farmacológico , Células HCT116 , Humanos , Ratones , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Fármacos Fotosensibilizantes/uso terapéutico , Polímeros/química , Polímeros/metabolismo , Profármacos/uso terapéuticoRESUMEN
Tumor-specific phototheranostics is conducive to realizing precise cancer therapy. Herein, a novel tumor microenvironment (TME)-responsive phototheranostic paradigm based on the combination of semiconducting polymer brushes and polyoxometalate clusters (SPB@POM) is rationally designed. The acidic TME could drive the self-assembly of SPB@POM into bigger aggregates for enhanced tumor retention and accumulation, while the reducing TME could significantly enhance the NIR absorption of SPB@POM for significant improvement of photoacoustic imaging contrast and photothermal therapy efficacy. Therefore, the smart pH/glutathione (GSH)-responsive SPB@POM allows for remarkable phototheranostic enhancement under the unique TME, which has potential for precise tumor-specific phototheranostics with minimal side effects.
Asunto(s)
Glutatión/química , Neoplasias/terapia , Fototerapia/métodos , Polímeros/química , Semiconductores , Nanomedicina Teranóstica , Compuestos de Tungsteno/química , Humanos , Concentración de Iones de Hidrógeno , Microscopía Electrónica de Transmisión , Polimerizacion , Espectroscopía Infrarroja Corta , Microambiente TumoralRESUMEN
Nanomedicines with photodynamic therapy and reactive oxygen species (ROS)-triggered drug release capabilities are promising for cancer therapy. However, most of the nanomedicines based on ROS-responsive nanocarriers still suffer from serious ROS consumption during the triggered drug release process. Herein, a photodynamic-chemodynamic cascade strategy for the design of drug delivery nanosystem is proposed. A doxorubicin hydrochloride-loaded ROS-responsive polymersome (DOX-RPS) is prepared via the self-assembly of amphiphilic poly(ethylene glycol)-poly(linoleic acid) and poly(ethylene glycol)-(2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-α)-iron chelate (PEG-HPPH-Fe). The RPS can effectively deliver a drug to tumor site through passive targeting effect. Upon laser irradiation, the photosensitizer HPPH can efficiently generate ROS, which further causes in situ oxidation of linoleic acid chain and subsequent RPS structural destruction, permitting triggered drug release. Intriguingly, catalyzed by HPPH-Fe, ROS will be regenerated from linoleic acid peroxide through a chemodynamic process. Therefore, ROS-triggered drug release can be achieved without ROS over-consumption. The in vitro and in vivo results confirmed ROS generation, triggered drug release behavior, and potent antitumor effect of the DOX-RPS. This photodynamic-chemodynamic cascade strategy provides a promising approach for enhanced combination therapy.
Asunto(s)
Doxorrubicina/farmacología , Sistemas de Liberación de Medicamentos/métodos , Glioma/terapia , Nanopartículas/administración & dosificación , Fotoquimioterapia/métodos , Polietilenglicoles/química , Especies Reactivas de Oxígeno/metabolismo , Animales , Antibióticos Antineoplásicos/farmacología , Línea Celular Tumoral , Terapia Combinada , Liberación de Fármacos , Glioma/metabolismo , Glioma/patología , Humanos , Ratones Desnudos , Nanopartículas/química , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Tensoactivos/química , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Zwitterionic surface modification is a promising strategy for nanomedicines to achieve prolonged circulation time and thus effective tumor accumulation. However, zwitterion modified nanoparticles suffer from reduced cellular internalization efficiency. Methods: A polyprodrug-based nanomedicine with zwitterionic-to-cationic charge conversion ability (denoted as ZTC-NMs) was developed for enhanced chemotherapeutic drug delivery. The polyprodrug consists of pH-responsive poly(carboxybetaine)-like zwitterionic segment and glutathione-responsive camptothecin prodrug segment. Results: The ZTC-NMs combine the advantages of zwitterionic surface and polyprodrug. Compared with conventional zwitterionic surface, the ZTC-NMs can respond to tumor microenvironment and realize ZTC surface charge conversion, thus improve cellular internalization efficiency of the nanomedicines. Conclusions: This ZTC method offers a strategy to promote the drug delivery efficiency and therapeutic efficacy, which is promising for the development of cancer nanomedicines.
Asunto(s)
Camptotecina/farmacología , Cationes/química , Sistemas de Liberación de Medicamentos/métodos , Neoplasias Pulmonares/tratamiento farmacológico , Nanopartículas/química , Polímeros/química , Profármacos/farmacología , Animales , Antineoplásicos Fitogénicos/farmacología , Línea Celular Tumoral , Humanos , Neoplasias Pulmonares/patología , Ratones , Ratones Desnudos , Nanomedicina , Nanopartículas/administración & dosificación , Profármacos/química , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Combination therapy with multiple chemotherapeutic agents is the main approach for cancer treatment in the clinic. Polyphenol-based materials are found in our diet, demonstrate good biocompatibility, and prevent numerous diseases. In this study, we encapsulate two drugs in a single polyphenol-based polymer with Fe3+ or Mn2+ ions as the cross-linker for cancer therapy. The combination index of two drugs is an essential parameter to evaluate drug combinations. The amphiphilic polymer poly(ethylene glycol)-block-polydopamine (PEG-PDA) was prepared by RAFT polymerization. The nanoparticles were prepared via self-assembly with Fe3+ or Mn2+ ions. Both doxorubicin (DOX) and simvastatin (SV) were encapsulated in the core of the nanoparticles. The cell viability and combination index were evaluated in vitro. The tumor accumulation of the nanoparticles was investigated by positron-emission tomography (PET) and magnetic resonance (MR) imaging. The as-prepared nanoparticles exhibited high drug loading capacity. The drug loaded nanoparticles could kill cancer cells effectively with a combination index <1. Both PET and MRI revealed that the nanoparticles showed long blood circulation time and high tumor accumulation. The nanoparticles could inhibit tumor inhibition via intravenous injection of nanoparticles. The polyphenol-based nanoplatform may serve as a promising theranostic candidate for clinical application.
Asunto(s)
Portadores de Fármacos/uso terapéutico , Nanopartículas/uso terapéutico , Neoplasias/tratamiento farmacológico , Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/administración & dosificación , Liberación de Fármacos , Humanos , Polietilenglicoles/química , Simvastatina/administración & dosificación , Nanomedicina Teranóstica/métodosRESUMEN
The success of radiotherapy relies on tumor-specific delivery of radiosensitizers to attenuate hypoxia resistance. Here we report an ammonia-assisted hot water etching strategy for the generic synthesis of a library of small-sized (sub-50 nm) hollow mesoporous organosilica nanoparticles (HMONs) with mono, double, triple, and even quadruple framework hybridization of diverse organic moieties by changing only the introduced bissilylated organosilica precursors. The biodegradable thioether-hybridized HMONs are chosen for efficient co-delivery of tert-butyl hydroperoxide (TBHP) and iron pentacarbonyl (Fe(CO)5). Distinct from conventional RT, radiodynamic therapy (RDT) is developed by taking advantage of X-ray-activated peroxy bond cleavage within TBHP to generate â¢OH, which can further attack Fe(CO)5 to release CO molecules for gas therapy. Detailed in vitro and in vivo studies reveal the X-ray-activated cascaded release of â¢OH and CO molecules from TBHP/Fe(CO)5 co-loaded PEGylated HMONs without reliance on oxygen, which brings about remarkable destructive effects against both normoxic and hypoxic cancers.
Asunto(s)
Antineoplásicos/administración & dosificación , Quimioradioterapia/métodos , Portadores de Fármacos/síntesis química , Liberación de Fármacos/efectos de la radiación , Neoplasias/terapia , Animales , Monóxido de Carbono/química , Femenino , Células Hep G2 , Humanos , Radical Hidroxilo/química , Radical Hidroxilo/efectos de la radiación , Compuestos de Hierro/administración & dosificación , Ratones , Ratones Desnudos , Nanopartículas/química , Compuestos de Organosilicio/síntesis química , Tamaño de la Partícula , Polietilenglicoles/química , Porosidad , Células RAW 264.7 , Resultado del Tratamiento , Rayos X , Ensayos Antitumor por Modelo de Xenoinjerto , terc-Butilhidroperóxido/administración & dosificación , terc-Butilhidroperóxido/efectos de la radiaciónRESUMEN
The development of smart theranostic systems with favourable biocompatibility, high loading efficiency, excellent circulation stability, potent anti-tumour activity, and multimodal diagnostic functionalities is of importance for future clinical application. The premature burst release and poor degradation kinetics indicative of polymer-based nanomedicines remain the major obstacles for clinical translation. Herein we prepare theranostic shell-crosslinked nanoparticles (SCNPs) using a ß-cyclodextrin-based polyrotaxane (PDI-PCL-b-PEG-RGDâß-CD-NH2) to avoid premature drug leakage and achieve precisely controllable release, enhancing the maximum tolerated dose of the supramolecular nanomedicines. cRGDfK and perylene diimide are chosen as the stoppers of PDI-PCL-b-PEG-RGDâß-CD-NH2, endowing the resultant SCNPs with excellent integrin targeting ability, photothermal effect, and photoacoustic capability. In vivo anti-tumour studies demonstrate that drug-loaded SCNPs completely eliminate the subcutaneous tumours without recurrence after a single-dose injection combining chemotherapy and photothermal therapy. These supramolecular nanomedicines also exhibit excellent anti-tumour performance against orthotopic breast cancer and prevent lung metastasis with negligible systemic toxicity.
Asunto(s)
Antineoplásicos/química , Ciclodextrinas/química , Sistemas de Liberación de Medicamentos/métodos , Neoplasias/tratamiento farmacológico , Poloxámero/química , Rotaxanos/química , Nanomedicina Teranóstica/métodos , Animales , Antineoplásicos/administración & dosificación , Línea Celular Tumoral , Doxorrubicina/administración & dosificación , Doxorrubicina/química , Sistemas de Liberación de Medicamentos/instrumentación , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Nanopartículas/química , Neoplasias/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Nanomedicina Teranóstica/instrumentación , beta-Ciclodextrinas/químicaRESUMEN
Minimizing the sequestration of nanomaterials (NMs) by the reticuloendothelial system (RES) can enhance the circulation time of NMs, and thus increase their tumor-specific accumulation. Liposomes are generally regarded as safe (GRAS) agents that can block the RES reversibly and temporarily. With the help of positron emission tomography (PET), we monitored the in vivo tissue distribution of 64Cu-labeled 40 × 10 nm gold nanorods (Au NRs) after pretreatment with liposomes. We systematically studied the effectiveness of liposome administration by comparing (1) differently charged liposomes; (2) different liposome doses; and (3) varying time intervals between liposome dose and NR dose. By pre-injecting 400 µmol/kg positively charged liposomes into mice 5 h before the Au NRs, the liver and spleen uptakes of Au NRs decreased by 30% and 53%, respectively. Significantly, U87MG tumor uptake of Au NRs increased from 11.5 ± 1.1 %ID/g to 16.1 ± 1.3 %ID/g at 27 h post-injection. Quantitative PET imaging is a valuable tool to understand the fate of NMs in vivo and cationic liposomal pretreatment is a viable approach to reduce RES clearance, prolong circulation, and improve tumor uptake.
Asunto(s)
Antineoplásicos/administración & dosificación , Antineoplásicos/farmacocinética , Glioblastoma/tratamiento farmacológico , Oro/administración & dosificación , Liposomas/administración & dosificación , Sistema Mononuclear Fagocítico/metabolismo , Nanopartículas/administración & dosificación , Animales , Radioisótopos de Cobre/administración & dosificación , Modelos Animales de Enfermedad , Hígado/diagnóstico por imagen , Ratones , Tomografía de Emisión de Positrones , Bazo/diagnóstico por imagenRESUMEN
Semiconducting molecules of perylene diimide (PDI) with strong light absorption properties in the near-infrared region and good biocompatibility have received increasing attention in the field of theranostics, especially as photoacoustic (PA) imaging agents. Herein, we report a series of [64Cu]-labeled PDI nanoparticles (NPs) of different sizes (30, 60, 100, and 200 nm) as dual positron emission tomography (PET) and PA imaging probes and photothermal therapy agents. The precise size control of the PDI NPs can be achieved by adjusting the initial concentration of PDI molecules in the self-assembly process, and the photophysical property of different sized PDI NPs was studied in detail. Furthermore, we systematically investigated the size-dependent accumulation of the PDI NPs in the lymphatic system after local administration and in tumors after intravenous injection by PA and PET imaging. The results revealed that 100 nm is the best size for differentiating popliteal and sciatic LNs since the interval is around 60 min for the NPs to migrate from popliteal LNs to sciatic LNs, which is an ideal time window to facilitate surgical sentinel LN biopsy and pathological examination. Furthermore, different migration times of the different-sized PDI NPs will provide more choices for surgeons to map the specific tumor relevant LNs. PDI NP theranostics can also be applied to imaging-guided cancer therapy. The NPs with a size of 60 nm appear to be the best for tumor imaging and photothermal cancer therapy due to the maximum tumor accumulation efficiency. Thus, our study not only presents organic PDI NP theranostics but also introduces different-sized NPs for multiple bioapplications.
Asunto(s)
Imidas/química , Ganglios Linfáticos/metabolismo , Nanopartículas/química , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Perileno/análogos & derivados , Células 3T3 , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Supervivencia Celular , Medios de Contraste/química , Radioisótopos de Cobre , Humanos , Ganglios Linfáticos/diagnóstico por imagen , Ratones , Ratones Desnudos , Imagen Multimodal , Tamaño de la Partícula , Perileno/química , Técnicas Fotoacústicas/métodos , Polietilenglicoles/química , Tomografía de Emisión de Positrones/métodos , Semiconductores , Distribución TisularRESUMEN
Reported procedures on the synthesis of gold nanoshells with smooth surfaces have merely demonstrated efficient control of shell thickness and particle size, yet no branch and nanoporous features on the nanoshell have been implemented to date. Herein, we demonstrate the ability to control the roughness and nanoscale porosity of gold nanoshells by using redox-active polymer poly(vinylphenol)-b-(styrene) nanoparticles as reducing agent and template. The porosity and size of the branches on this branched nanoporous gold nanoshell (BAuNSP) material can be facilely adjusted by control of the reaction speed or the reaction time between the redox-active polymer nanoparticles and gold ions (Au3+). Due to the strong reduction ability of the redox-active polymer, the yield of BAuNSP was virtually 100%. By taking advantage of the sharp branches and nanoporous features, BAuNSP exhibited greatly enhanced physico-optical properties, including photothermal effect, surface-enhanced Raman scattering (SERS), and photoacoustic (PA) signals. The photothermal conversion efficiency can reach as high as 75.5%, which is greater than most gold nanocrystals. Furthermore, the nanoporous nature of the shells allows for effective drug loading and controlled drug release. The thermoresponsive polymer coated on the BAuNSP surface serves as a gate keeper, governing the drug release behavior through photothermal heating. Positron emission tomography imaging demonstrated a high passive tumor accumulation of 64Cu-labeled BAuNSP. The strong SERS signal generated by the SERS-active BAuNSP in vivo, accompanied by enhanced PA signals in the tumor region, provide significant tumor information, including size, morphology, position, and boundaries between tumor and healthy tissues. In vivo tumor therapy experiments demonstrated a highly synergistic chemo-photothermal therapy effect of drug-loaded BAuNSPs, guided by three modes of optical imaging.
Asunto(s)
Oro/química , Nanoporos , Nanocáscaras/química , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Polímeros/química , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/uso terapéutico , Sistemas de Liberación de Medicamentos/métodos , Femenino , Oro/uso terapéutico , Humanos , Hipertermia Inducida/métodos , Ratones , Nanoporos/ultraestructura , Nanocáscaras/uso terapéutico , Nanocáscaras/ultraestructura , Imagen Óptica/métodos , Oxidación-Reducción , Técnicas Fotoacústicas/métodos , Fototerapia/métodos , Polímeros/uso terapéutico , Tomografía de Emisión de Positrones/métodosRESUMEN
Integration of magnetic resonance imaging (MRI) and other imaging modalities is promising to furnish complementary information for accurate cancer diagnosis and imaging-guided therapy. However, most gadolinium (Gd)-chelator MR contrast agents are limited by their relatively low relaxivity and high risk of released-Gd-ions-associated toxicity. Herein, a radionuclide-64 Cu-labeled doxorubicin-loaded polydopamine (PDA)-gadolinium-metallofullerene core-satellite nanotheranostic agent (denoted as CDPGM) is developed for MR/photoacoustic (PA)/positron emission tomography (PET) multimodal imaging-guided combination cancer therapy. In this system, the near-infrared (NIR)-absorbing PDA acts as a platform for the assembly of different moieties; Gd3 N@C80 , a kind of gadolinium metallofullerene with three Gd ions in one carbon cage, acts as a satellite anchoring on the surface of PDA. The as-prepared CDPGM NPs show good biocompatibility, strong NIR absorption, high relaxivity (r 1 = 14.06 mM-1 s-1 ), low risk of release of Gd ions, and NIR-triggered drug release. In vivo MR/PA/PET multimodal imaging confirms effective tumor accumulation of the CDPGM NPs. Moreover, upon NIR laser irradiation, the tumor is completely eliminated with combined chemo-photothermal therapy. These results suggest that the CDPGM NPs hold great promise for cancer theranostics.
Asunto(s)
Indoles/química , Polímeros/química , Gadolinio , Humanos , Imagen Multimodal , Neoplasias , FototerapiaRESUMEN
A versatile biomimetic theranostic agent based on magnetic melanin nanoparticles is developed for positron-emission tomography/magnetic resonance/photoacoustic/photothermal multimodal-imaging-guided cancer photothermal therapy and UV and γ-irradiation protection.
Asunto(s)
Materiales Biocompatibles/uso terapéutico , Rayos gamma , Neoplasias/terapia , Fototerapia , Nanomedicina Teranóstica , Rayos Ultravioleta , Animales , Materiales Biocompatibles/química , Línea Celular Tumoral , Supervivencia Celular , Cobre/química , Rayos gamma/uso terapéutico , Humanos , Imagen por Resonancia Magnética , Melaninas/química , Ratones , Ratones Desnudos , Nanopartículas/química , Nanopartículas/uso terapéutico , Nanopartículas/toxicidad , Neoplasias/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía de Emisión de Positrones , Radiofármacos/química , Trasplante HeterólogoRESUMEN
A new kind of ultrasmall dissociable AuNR@PEG/PLGA vesicles (≈60 nm) (AuNR = gold nanorod; PEG = poly(ethylene glycol); PLGA = poly(lactic-co-glycolic acid)) assembled from small AuNRs (dimension: ≈8 nm × 2 nm) is reported. They exhibit several striking features: prolonged circulation and prominent tumor accumulation; rapid excretion from the body as AuNR@PEG after therapy; enhanced photoacoustic and photo thermal properties; and high photothermal cancer therapy efficacy.
Asunto(s)
Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/terapia , Oro/química , Oro/metabolismo , Nanotubos , Nanomedicina Teranóstica , Animales , Neoplasias Encefálicas/diagnóstico , Línea Celular Tumoral , Oro/farmacocinética , Humanos , Cinética , Ácido Láctico/química , Ratones , Técnicas Fotoacústicas , Polietilenglicoles/química , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico-Ácido PoliglicólicoRESUMEN
Using positron emission tomography (PET) imaging to monitor and quantitatively analyze the delivery and localization of Au nanomaterials (NMs), a widely used photothermal agent, is essential to optimize therapeutic protocols to achieve individualized medicine and avoid side effects. Coupling radiometals to Au NMs via a chelator faces the challenges of possible detachment of the radiometals as well as surface property changes of the NMs. In this study, we reported a simple and general chelator-free (64)Cu radiolabeling method by chemically reducing (64)Cu on the surface of polyethylene glycol (PEG)-stabilized Au NMs regardless of their shape and size. Our (64)Cu-integrated NMs are proved to be radiochemically stable and can provide an accurate and sensitive localization of NMs through noninvasive PET imaging. We further integrated (64)Cu onto arginine-glycine-aspartic acid (RGD) peptide modified Au nanorods (NRs) for tumor theranostic application. These NRs showed high tumor targeting ability in a U87MG glioblastoma xenograft model and were successfully used for PET image-guided photothermal therapy.