RESUMEN
In recent decade, palladium-based (Pd-based) nanomaterials have shown significant potential for biomedical applications because of their unique optical properties, excellent biocompatibility and high stability in physiological environment. Compared with other intensively studied noble nanomaterials, such as gold (Au) and silver (Ag) nanomaterials, research on Pd-based nanomaterials started late, but the distinctive features, such as high photothermal conversion efficiency and high photothermal stability, have made them getting great attention in the field of nanomedicine. The goal of this review is to provide a comprehensive and critical perspective on the recent progress of Pd-based nanomaterials as imaging contrast agents and therapeutic agents. The imaging section focuses on applications in photoacoustic (PA) imaging, single-photon emission computed tomography (SPECT) imaging, computed tomography (CT) imaging and magnetic resonance (MR) imaging. For treatment of cancer, single photothermal therapy (PTT) and PTT combined with other therapeutic modalities will be discussed. Finally, the safety concerns, forthcoming challenges and perspective of Pd-based nanomaterials on biomedical applications will be presented.
Asunto(s)
Diagnóstico por Imagen/métodos , Nanoestructuras/química , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Paladio/química , Animales , Medios de Contraste/administración & dosificación , Humanos , Fototerapia/métodosRESUMEN
To circumvent the huge cost, long R&D time and the difficulty to identify the targets of new drugs, repurposing the ones that have been clinically approved has been considered as a viable strategy to treat different diseases. In the current study, we outlined the rationale for repurposing disulfiram (DSF, an old alcohol-aversion drug) to treat primary breast cancer and its metastases. Methods: To overcome a few shortcomings of the individual administration of DSF, such as the dependence on copper ions (Cu2+) and limited capability in selective targeting, we here artificially synthesized the active form of DSF, diethyldithiocarbamate (DTC)-Cu complex (CuET) for cancer therapeutics. To achieve a greater efficacy in vivo, smart nanomedicines were devised through a one-step self-assembly of three functional components including a chemically stable and biocompatible phase-change material (PCM), the robust anticancer drug (CuET) and a near-infrared (NIR) dye (DIR), namely CuET/DIR NPs. A number of in vitro assays were performed including the photothermal efficacy, light-triggered drug release behavior, nuclear localization, DNA damage and induction of apoptosis of CuET/DIR NPs and molecular mechanisms underlying CuET-induced repression on cancer metastatic behaviors. Meanwhile, the mice bearing 4T1-LG12-drived orthotopic tumors were employed to evaluate in vivo biodistribution and anti-tumor effect of CuET/DIR NPs. The intravenous injection model was employed to reflect the changes of the intrinsic metastatic propensity of 4T1-LG12 cells responding to CuET/DIR NPs. Results: The rationally designed nanomedicines have self-traceability for bioimaging, long blood circulation time for enhanced drug accumulation in the tumor site and photo-responsive release of the anticancer drugs. Moreover, our data unearthed that CuET/DIR nanomedicines behave like "Trojan horse" to transport CuET into the cytoplasm, realizing substantial intracellular accumulation. Upon NIR laser irradiation, massive CuET would be triggered to release from the nanomedicines and reach a high local concentration towards the nucleus, where the pro-apoptotic effects were conducted. Importantly, our CuET/DIR nanomedicines revealed a pronounced capability to leash breast cancer metastases through inhibition on EMT. Additionally, these nanomedicines showed great biocompatibility in animals. Conclusion: These combined data unearthed a remarkably enhanced tumor-killing efficacy of our CuET nanomedicines through nuclear targeting. This work may open a new research area of repurposing DSF as innovative therapeutic agents to treat breast cancer and its metastases.
Asunto(s)
Antineoplásicos/farmacología , Cobre , Disulfiram , Ditiocarba , Nanopartículas , Animales , Antineoplásicos/química , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral/efectos de los fármacos , Núcleo Celular , Cobre/química , Cobre/farmacología , Disulfiram/química , Disulfiram/farmacología , Ditiocarba/química , Ditiocarba/farmacología , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Reposicionamiento de Medicamentos , Femenino , Humanos , Terapia por Luz de Baja Intensidad , Ratones , Nanomedicina , Nanopartículas/química , Nanopartículas/uso terapéutico , Metástasis de la Neoplasia/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Nanomedicina Teranóstica/métodosRESUMEN
Ultrasound (US)-driven sonodynamic therapy (SDT) has demonstrated wide application prospects in the eradication of deep-seated bacterial infections due to its noninvasiveness, site-confined irradiation, and high-tissue-penetrating capability. However, the ineffective accumulation of sonosensitizers at the infection site, the hypoxic microenvironment, as well as rapid depletion of oxygen during SDT greatly hamper the therapeutic efficacy of SDT. Herein, an US-switchable nanozyme system was proposed for the controllable generation of catalytic oxygen and sonosensitizer-mediated reactive oxygen species during ultrasound activation, thereby alleviating the hypoxia-associated barrier and augmenting SDT efficacy. This nanoplatform (Pd@Pt-T790) was easily prepared by bridging enzyme-catalytic Pd@Pt nanoplates with the organic sonosensitizer meso-tetra(4-carboxyphenyl)porphine (T790). It was really interesting to find that the modification of T790 onto Pd@Pt could significantly block the catalase-like activity of Pd@Pt, whereas upon US irradiation, the nanozyme activity was effectively recovered to catalyze the decomposition of endogenous H2O2 into O2. Such "blocking and activating" enzyme activity was particularly important for decreasing the potential toxicity and side effects of nanozymes on normal tissues and has potential to realize active, controllable, and disease-loci-specific nanozyme catalytic behavior. Taking advantage of this US-switchable enzyme activity, outstanding accumulation in infection sites, as well as excellent biocompatibility, the Pd@Pt-T790-based SDT nanosystem was successfully applied to eradicate methicillin-resistant Staphylococcus aureus (MRSA)-induced myositis, and the sonodynamic therapeutic progression was noninvasively monitored by photoacoustic imaging and magnetic resonance imaging. The developed US-switchable nanoenzyme system provides a promising strategy for augmenting sonodynamic eradication of deep-seated bacterial infection actively, controllably, and precisely.
Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Compuestos Organometálicos/farmacología , Infecciones Estafilocócicas/tratamiento farmacológico , Terapia por Ultrasonido , Animales , Antibacterianos/síntesis química , Antibacterianos/química , Supervivencia Celular/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos BALB C , Pruebas de Sensibilidad Microbiana , Imagen Óptica , Compuestos Organometálicos/síntesis química , Compuestos Organometálicos/química , Paladio/química , Paladio/farmacología , Tamaño de la Partícula , Platino (Metal)/química , Platino (Metal)/farmacología , Porfirinas/química , Porfirinas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Infecciones Estafilocócicas/metabolismo , Propiedades de Superficie , Ondas UltrasónicasRESUMEN
Palladium nanosheets (Pd NSs) have recently attracted increasing research interest in the biomedical field due to their excellent near-infrared absorption, photothermal conversion capability and biocompatibility. However, the application of Pd NSs in immunotherapy has not been reported. Here, Pd NSs were used as the carriers of immunoadjuvant CpG ODNs for not only efficient delivery of CpG but also for enhancing the immunotherapeutic effects of CpG by the Pd NS-based photothermal therapy (PTT). Pd NSs had no influence on the immune system, and the prepared Pd-CpG nanocomposites, especially Pd(5)-CpG(PS), could significantly increase the uptake of CpG by immune cells and enhance the immunostimulatory activity of CpG in vitro and in vivo. With the combination of Pd(5)-CpG(PS) mediated PTT and immunotherapy, highly efficient tumor inhibition was achieved and the survival rate of the tumor-bearing mice was greatly increased depending on Pd(5)-CpG(PS) with safe near-infrared (NIR) irradiation (808 nm laser, 0.15 W cm-2). Importantly, the combination therapy induced tumor cell death and released tumor-associated antigens, which could be effectively taken up and presented by antigen presenting cells with the assistance of CpG, leading to increased TNF-α and IL-6 production and enhanced cytotoxic T lymphocyte (CTL) activity. This work provides a new paradigm of utilizing photothermal nanomaterials for safe and highly efficient cancer photothermal combined immunotherapy.
Asunto(s)
Antineoplásicos , Inmunoterapia/métodos , Nanocompuestos/química , Oligodesoxirribonucleótidos , Fototerapia/métodos , Adyuvantes Inmunológicos/química , Adyuvantes Inmunológicos/farmacocinética , Adyuvantes Inmunológicos/farmacología , Animales , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Citocinas/metabolismo , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Nanomedicina/métodos , Neoplasias Experimentales/terapia , Oligodesoxirribonucleótidos/química , Oligodesoxirribonucleótidos/farmacocinética , Oligodesoxirribonucleótidos/farmacología , Paladio/química , Células RAW 264.7RESUMEN
In this work, a novel nanoplatform based on Pd corolla-human serum albumin-indocyanine green (PdCs-HSA-ICG) was developed for cancer photothermal/photodynamic combination therapy. Pd corollas (denoted as PdCs) with good near-infrared photothermal conversion efficiency (η≈ 37%) were first prepared and modified with human serum albumin (HSA) and indocyanine green (ICG) to get the PdCs-HSA-ICG nanocomposite. The prepared PdCs-HSA-ICG not only improves the colloid and thermal stability of ICG, but also shows a higher temperature increase than that of PdCs and free ICG as well as a comparable singlet oxygen (1O2) generation capability to that of free ICG. Upon single 808 nm laser irradiation, the photothermal (PTT)/photodynamic (PDT) combined therapeutic efficacy of PdCs-HSA-ICG at both cellular and animal levels was superior to PdCs-HSA (PTT) or free ICG (PTT and PDT), respectively. Thus, the designed PdCs-HSA-ICG nanocomposite holds great potential as a new class of photosensitive agent for cancer phototherapy.
RESUMEN
Owing to the excellent near infrared (NIR) light absorption and efficient passive targeting toward tumor tissue, two-dimensional (2D) core-shell PEGylated Pd@Au nanoplates have great potential in both photothermal therapy and drug delivery systems. In this work, we successfully conjugate Pd@Au nanoplates with a platinum(IV) prodrug c,c,t-[Pt(NH3)2Cl2(O2CCH2CH2CO2H)2] to obtain a nanocomposite (Pd@Au-PEG-Pt) for combined photothermal-chemotherapy. The prepared Pd@Au-PEG-Pt nanocomposite showed excellent stability in physiological solutions and efficient Pt(IV) prodrug loading. Once injected into biological tissue, the Pt(IV) prodrug was easily reduced by physiological reductants (e.g. ascorbic acid or glutathione) into its cytotoxic and hydrophilic Pt(II) form and released from the original nanocomposite, and the NIR laser irradiation could accelerate the release of Pt(II) species. More importantly, Pd@Au-PEG-Pt has high tumor accumulation (29%ID per g), which makes excellent therapeutic efficiency at relatively low power density possible. The in vivo results suggested that, compared with single therapy the combined thermo-chemotherapy treatment with Pd@Au-PEG-Pt resulted in complete destruction of the tumor tissue without recurrence, while chemotherapy using Pd@Au-PEG-Pt without irradiation or photothermal treatment using Pd@Au-PEG alone did not. Our work highlights the prospects of a feasible drug delivery strategy of the Pt prodrug by using 2D Pd@Au nanoplates as drug delivery carriers for multimode cancer treatment.
Asunto(s)
Antineoplásicos/administración & dosificación , Quimioterapia/métodos , Oro/química , Nanocompuestos/química , Neoplasias/tratamiento farmacológico , Fototerapia/métodos , Platino (Metal)/química , Profármacos/química , Animales , Ácido Ascórbico/química , Línea Celular , Cisplatino/química , Portadores de Fármacos , Sistemas de Liberación de Medicamentos/métodos , Femenino , Glutatión/química , Células HeLa , Humanos , Nanopartículas del Metal/química , Ratones , Ratones Endogámicos BALB C , Microscopía Electrónica de Transmisión , Nanotecnología , Espectroscopía Infrarroja CortaRESUMEN
Palladium nanosheets with strong near-infrared absorption have been recently demonstrated as promising photothermal agents for photothermal therapy (PTT) of cancers. However, systematic assessments of their potential risks and impacts to biological systems have not been fully explored yet. In this work, we carefully investigate how surface coatings affect the in vivo behaviors of small Pd nanosheets (Pd NSs). Several biocompatible molecules such as carboxymethyl chitosan (CMC), PEG-NH2, PEG-SH, and dihydrolipoic acid-zwitterion (DHLA-ZW) were used to coat Pd NSs. The blood circulation half-lives, biodistribution, potential toxicity, clearance, and photothermal effect of different surface-coated Pd NSs in mice after intravenous injection were compared. PEG-SH-coated Pd NSs (Pd-HS-PEG) were found to have ultralong blood circulation half-life and show high uptake in the tumor. We then carry out the in vivo photothermal therapeutic studies on the Pd-HS-PEG conjugate and revealed its outstanding efficacy in in vivo photothermal therapy of cancers. Our results highlight the importance of surface coatings to the in vivo behaviors of nanomaterials and can provide guidelines to the future design of Pd NSs bioconjugates for other in vivo applications.
Asunto(s)
Materiales Biocompatibles/química , Nanoestructuras/química , Paladio/química , Fototerapia/métodos , Animales , Materiales Biocompatibles/farmacocinética , Materiales Biocompatibles/toxicidad , Quitosano , Femenino , Ratones , Nanoestructuras/toxicidad , Neoplasias/patología , Neoplasias/terapia , Paladio/farmacocinética , Paladio/toxicidad , Polietilenglicoles , Espectrofotometría Infrarroja , Propiedades de Superficie , Termografía , Distribución TisularRESUMEN
Uniform plasmonic Pd@Au core-shell bimetallic nanoplates are synthesized by seeded growth strategy. Surface modified with SH-PEG makes it good biocompatibility, prolonged blood circulation, and relatively high tumor accumulation. Enhanced tumor contrast effects can be obtained for in vivo photoacoustic/CT imaging after intravenous injection of Pd@Au-PEG. Moreover, efficient photothermal tumor ablation is achieved, guided by the imaging techniques. This work promises further exploration of the superiority of 2D nanostructures for in vivo biomedical applications.
Asunto(s)
Oro/química , Nanoestructuras/química , Paladio/química , Animales , Línea Celular Tumoral , Femenino , Humanos , Rayos Infrarrojos , Ratones , Ratones Endogámicos BALB C , Neoplasias/diagnóstico , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Técnicas Fotoacústicas , Fototerapia , Polietilenglicoles/química , Resonancia por Plasmón de Superficie , Tomografía Computarizada por Rayos X , Trasplante HeterólogoRESUMEN
Efficient renal clearance is of fundamentally important property of nanoparticles for their in vivo biomedical applications. In this work, we report the successful synthesis of ultra-small Pd nanosheets (SPNS) with an average diameter of 4.4 nm and their application in photothermal cancer therapy using a near infrared laser. The ultra-small Pd nanosheets have strong optical absorption in the NIR region and high photothermal conversion efficiency (52.0%) at 808 nm. After being surface-functionalized with reduced glutathione (GSH), the SPNS-GSH was administered to mice to investigate the biodistribution, photothermal efficacy and tumor ablation in vivo. The in vivo photothermal therapy studies clearly demonstrate that surface modification with GSH allows the nanosheets to exhibit prolonged blood circulation and thus high accumulation in tumors. Upon 808 nm NIR irradiation, the tumors can be completely ablated. More importantly, with the size below the renal filtration limit (<10 nm), the GSHylated Pd nanosheets can be nicely cleared from body through the renal excretion route and into urine. Together with the high efficacy of NIR photothermal therapy, the unique renal clearance properties make the ultra-small Pd nanosheets promising for practical use in photothermal cancer therapy.
Asunto(s)
Riñón/química , Neoplasias Hepáticas/tratamiento farmacológico , Nanopartículas/uso terapéutico , Paladio/química , Paladio/uso terapéutico , Fotoquimioterapia/métodos , Animales , Línea Celular Tumoral , Hipertermia Inducida/métodos , Rayos Infrarrojos/uso terapéutico , Neoplasias Hepáticas/patología , Membranas Artificiales , Ratones , Ratones Endogámicos BALB C , Nanopartículas/química , Nanopartículas/ultraestructura , Fototerapia/métodos , Resultado del TratamientoRESUMEN
A versatile system combining chemotherapy with photothermal therapy for cancer cells using Pd nanosheet-covered hollow mesoporous silica nanoparticles is reported. While the hollow mesoporous silica core can be used to load anticancer drugs (i.e., doxorubicin) for chemotherapy, the Pd nanosheets on the surface of particles can convert NIR light into heat for photothermal therapy. More importantly, the loading of Pd nanosheets on hollow mesoporous silica nanospheres can dramatically increase the amount of cellular internalization of the Pd nanosheets: almost 11 times higher than the unloaded Pd nanosheets. The as-prepared nanocomposites efficiently deliver both drugs and heat to cancer cells to improve the therapeutic efficiency with minimal side effects. Compared with chemotherapy or photothermal therapy alone, the combination of chemotherapy and phototherapy can significantly improve the therapeutic efficacy, exhibiting a synergistic effect.
Asunto(s)
Sistemas de Liberación de Medicamentos , Nanocáscaras , Neoplasias/terapia , Paladio , Dióxido de Silicio , Antineoplásicos/administración & dosificación , Terapia Combinada , Doxorrubicina/administración & dosificación , Células Hep G2 , Calor/uso terapéutico , Humanos , Nanocompuestos/administración & dosificación , Nanocompuestos/química , Nanocompuestos/ultraestructura , Nanocáscaras/administración & dosificación , Nanocáscaras/química , Nanocáscaras/ultraestructura , Nanotecnología , FototerapiaRESUMEN
Polypyrrole nanoparticles (PPy NPs) exhibit strong absorption in the near infrared (NIR) region. With an excellent photothermal efficiency of ~45% at 808 nm, sub-100 nm PPy NPs are demonstrated to be a promising photothermal agent for in vivo cancer therapy using NIR irradiation.
Asunto(s)
Rayos Infrarrojos , Nanopartículas/química , Polímeros/química , Pirroles/química , Animales , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Ratones , Nanopartículas/uso terapéutico , Nanopartículas/toxicidad , Neoplasias/terapia , Fototerapia , Distribución TisularAsunto(s)
Plomo/química , Nanopartículas del Metal/química , Plata/química , Línea Celular Tumoral , Hepatocitos/efectos de los fármacos , Hepatocitos/efectos de la radiación , Humanos , Rayos Infrarrojos , Neoplasias/terapia , Paladio/química , Fototerapia , Piridinas/química , Dióxido de Silicio/química , Espectrometría Raman , Resonancia por Plasmón de Superficie , TemperaturaRESUMEN
Thickness does matter! The ultrathin nature of 1.8 nm-thick Pd nanosheets prevents them entering cells effectively. A 13-times enhancement in the cells' uptake of the Pd nanosheets has now been achieved by silica coating together with surface functionalization, therefore significantly improving their NIR photothermal cell-killing efficacy.