RESUMEN
Photoacoustic imaging (PA) in the second near infrared (NIR-II) window presents key advantages for deep tissue imaging owing to reduced light scattering and low background signal from biological structures. Here, a thiadiazoloquinoxaline-based semiconducting polymer (SP) with strong absorption in the NIR-II region is reported. After encapsulation of SP in Pluronic F127 (F127) followed by removal of excess surfactant, a dual functional polymer system named surfactant-stripped semiconductor polymeric micelles (SSS-micelles) are generated with water solubility, storage stability, and high photothermal conversion efficiency, permitting tumor theranostics in a mouse model. SSS-micelles have a wideband absorption in the NIR-II window, allowing for the PA imaging at both 1064 and 1300 nm wavelengths. The PA signal of the SSS-micelles can be detected through 6.5 cm of chicken breast tissue in vitro. In mice or rats, SSS-micelles can be visualized in bladder and intestine overlaid 5 cm (signal to noise ratio, SNR ≈ 17 dB) and 5.8 cm (SNR over 10 dB) chicken breast tissue, respectively. This work demonstrates the SSS-micelles as a nanoplatform for deep tissue theranostics.
Asunto(s)
Nanopartículas , Neoplasias , Técnicas Fotoacústicas , Animales , Ratones , Micelas , Nanopartículas/química , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Técnicas Fotoacústicas/métodos , Fototerapia , Polímeros/química , Medicina de Precisión , Ratas , Tensoactivos/químicaRESUMEN
Janus nanogap gold nanoparticles (JAuNNPs) with varying proportions of Au shell coverage of (ca. 100/75/50/25 %) are presented. The internal nanogap between the partial Au shell and core caused asymmetric optical behavior; tunability depends on the degree of Au shell coverage and structural asymmetry. The shell-to-shell or core-to-core JAuNNDs(50 %) were self-assembled from amphiphilic JAuNNPs(50 %) by tuning the hydrophilic and hydrophobic polymer brushes on the Au core or shell. The positions of electromagnetic field enhancement of JAuNNDs varied with geometrical configurations because of hybridized plasmonic coupling effects. Furthermore, DNA linkers were utilized to form JAuNND12 (50 %). By combining with Raman molecules, ratiometric SERS signals could be generated, enabling JAuNND12 (50 %) to image the distribution of miR-21 in living cells and tumors. Asymmetric JAuNNPs allowed facile conjugation of various linkage molecules to fabricate dimeric nanostructures.
Asunto(s)
Oro/química , Nanopartículas del Metal/química , MicroARNs/análisis , Espectrometría Raman/métodos , Animales , Línea Celular Tumoral , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Ratones , Ratones Desnudos , MicroARNs/metabolismo , Microscopía Electrónica de Transmisión , Neoplasias/genética , Neoplasias/patología , Polímeros/química , Trasplante HeterólogoRESUMEN
In the present study, we report the development of magnetic-plasmonic bilayer vesicles assembled from iron oxide-gold Janus nanoparticles (Fe3O4-Au JNPs) for reactive oxygen species (ROS) enhanced chemotherapy. The amphiphilic Fe3O4-Au JNPs were grafted with poly(ethylene glycol) (PEG) on the Au surface and ROS-generating poly(lipid hydroperoxide) (PLHP) on the Fe3O4 surface, respectively, which were then assembled into vesicles containing two closely attached Fe3O4-Au NPs layers in opposite directions. The self-assembly mechanism of the bilayered vesicles was elucidated by performing a series of numerical simulations. The enhanced optical properties of the bilayered vesicles were verified by the calculated results and experimental data. The vesicles exhibited enhanced T2 relaxivity and photoacoustic properties over single JNPs due to the interparticle magnetic dipole interaction and plasmonic coupling. In particular, the vesicles are pH responsive and disassemble into single JNPs in the acidic tumor environment, activating an intracellular biochemical reaction between the grafted PLHP and released ferrous ions (Fe2+) from Fe3O4 NPs, resulting in highly efficient local ROS generation and increased intracellular oxidative stress. In combination with the release of doxorubicin (DOX), the vesicles combine ROS-mediated cytotoxicity and DOX-induced chemotherapy, leading to greatly improved therapeutic efficacy than monotherapies. High tumor accumulation efficiency and fast vesicle clearance from the body were also confirmed by positron emission tomography (PET) imaging of radioisotope 64Cu-labeled vesicles.
Asunto(s)
Antineoplásicos/uso terapéutico , Doxorrubicina/uso terapéutico , Portadores de Fármacos/química , Nanopartículas de Magnetita/uso terapéutico , Neoplasias/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Antineoplásicos/farmacocinética , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Doxorrubicina/farmacocinética , Liberación de Fármacos , Sinergismo Farmacológico , Oro/química , Humanos , Concentración de Iones de Hidrógeno , Peróxidos Lipídicos/química , Imagen por Resonancia Magnética/métodos , Nanopartículas de Magnetita/química , Técnicas Fotoacústicas/métodos , Polietilenglicoles/química , Pirenos/química , Oxígeno Singlete/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
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
Plasmonic nanostructures with unique physical and biological properties have attracted increased attention for potential biomedical applications. Polymers grafted on metal nanoparticle surface can be used as assembly regulating molecules to guide nanoparticles organize into ordered or hierarchical structures in solution, within condensed phases, or at interfaces. In this Topical Review, we will highlight recent efforts on self-assembly of gold nanoparticles coated with polymer brushes. How and what kind of polymer graft can be used to adjust nanoparticle interactions, to dictate interparticle orientation, and to determine assembled nanostructures will be discussed. Furthermore, the Topical Review will shed light on the physicochemical properties, including self-assembly behavior and kinetics, tunable localized surface plasmon resonance effect, enhanced surface enhanced Raman scattering, and other optical and thermal properties. The potential of self-assembled nanostructures for applications in different fields, especially in biomedicine, will also be elaborated.
Asunto(s)
Polímeros/química , Acústica , Espectrometría Raman , Resonancia por Plasmón de SuperficieRESUMEN
Janus nanoparticles (JNPs) offer unique features, including the precisely controlled distribution of compositions, surface charges, dipole moments, modular and combined functionalities, which enable excellent applications that are unavailable to their symmetrical counterparts. Assemblies of NPs exhibit coupled optical, electronic and magnetic properties that are different from single NPs. Herein, we report a new class of double-layered plasmonic-magnetic vesicle assembled from Janus amphiphilic Au-Fe3 O4 NPs grafted with polymer brushes of different hydrophilicity on Au and Fe3 O4 surfaces separately. Like liposomes, the vesicle shell is composed of two layers of Au-Fe3 O4 NPs in opposite direction, and the orientation of Au or Fe3 O4 in the shell can be well controlled by exploiting the amphiphilic property of the two types of polymers.
Asunto(s)
Compuestos Férricos/química , Oro/química , Magnetismo , Nanopartículas del Metal/química , Interacciones Hidrofóbicas e Hidrofílicas , Cinética , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , Polímeros/química , Espectroscopía de Protones por Resonancia Magnética , Espectrometría Raman , Resonancia por Plasmón de Superficie , Propiedades de Superficie , TermodinámicaRESUMEN
We report a new strategy to synthesize core-shell metal nanoparticles with an interior, Raman tag-encoded nanogap by taking advantage of nanoparticle-templated self-assembly of amphiphilic block copolymers and localized metal precursor reduction by redox-active polymer brushes. Of particular interest for surface-enhanced Raman scattering (SERS) is that the nanogap size can be tailored flexibly, with the sub-2 nm nanogap leading to the highest SERS enhancement. Our results have further demonstrated that surface functionalization of the nanogapped Au nanoparticles with aptamer targeting ligands allows for specific recognition and ultrasensitive detection of cancer cells. The general applicability of this new synthetic strategy, coupled with recent advances in controlled wet-chemical synthesis of functional nanocrystals, opens new avenues to multifunctional core-shell nanoparticles with integrated optical, electronic, and magnetic properties.
Asunto(s)
Oro/química , Nanopartículas del Metal/química , Polímeros/química , Espectrometría Raman/métodos , Aptámeros de Nucleótidos/química , Línea Celular Tumoral , Humanos , Nanopartículas del Metal/ultraestructura , Neoplasias/diagnóstico , Oxidación-Reducción , Propiedades de SuperficieRESUMEN
Large osseous void, postsurgical neoplastic recurrence, and slow bone-cartilage repair rate raise an imperative need to develop functional scaffold in clinical osteosarcoma treatment. Herein, a bionic bilayer scaffold constituting croconaine dye-polyethylene glycol@sodium alginate hydrogel and poly(l-lactide)/hydroxyapatite polymer matrix is fabricated to simultaneously achieve a highly efficient killing of osteosarcoma and an accelerated osteochondral regeneration. First, biomimetic osteochondral structure along with adequate interfacial interaction of the bilayer scaffold provide a structural reinforcement for transverse osseointegration and osteochondral regeneration, as evidenced by upregulated specific expressions of collagen type-I, osteopontin, and runt-related transcription factor 2. Meanwhile, thermal ablation of the synthesized nanoparticles and mitochondrial dysfunction caused by continuously released hydroxyapatite induce residual tumor necrosis synergistically. To validate the capabilities of inhibiting tumor growth and promoting osteochondral regeneration of our proposed scaffold, a novel orthotopic osteosarcoma model simulating clinical treatment scenarios of bone tumors is established on rats. Based on amounts of in vitro and in vivo results, an effective killing of osteosarcoma and a suitable osteal-microenvironment modulation of such bionic bilayer composite scaffold are achieved, which provides insightful implications for photonic hyperthermia therapy against osteosarcoma and following osseous tissue regeneration.
Asunto(s)
Hipertermia Inducida , Osteosarcoma , Ratas , Animales , Andamios del Tejido/química , Biónica , Materiales Biocompatibles/química , Durapatita/química , Regeneración Ósea , Osteosarcoma/terapia , Microambiente TumoralRESUMEN
We have developed a new class of plasmonic vesicular nanostructures assembled from amphiphilic gold nanocrystals with mixed polymer brush coatings. One major finding is that the integration of gold nanocrystals (nanoparticles and nanorods) with two types of chemically distinct polymer grafts, which are analogous to block copolymers as a whole, creates a new type of hybrid building block inheriting the amphiphilicity-driven self-assembly of block copolymers to form vesicular structures and the plasmonic properties of the nanocrystals. In contrast to other vesicular structures, the disruption of the plasmonic vesicles can be triggered by stimulus mechanisms inherent to either the polymer or the nanocrystal. Recent advances in nanocrystal synthesis and controlled surface-initiated polymerization have opened a wealth of possibilities for expanding this concept to other types of nanocrystals and integrating different types of nanocrystals into multifunctional vesicles. The development of multifunctional vesicles containing stimuli-responsive polymers could enable their broader applications in biosensing, multimodality imaging, and theragnostic nanomedicine.
Asunto(s)
Oro/química , Interacciones Hidrofóbicas e Hidrofílicas , Nanopartículas del Metal/química , Rayos Infrarrojos , Modelos Moleculares , Conformación Molecular , Polímeros/químicaRESUMEN
Janus nanoparticles (JNPs) refer to the integration of two or more chemically discrepant composites into one structure system. Studies into JNPs have been of significant interest due to their interesting characteristics stemming from their asymmetric structures, which can integrate different functional properties and perform more synergetic functions simultaneously. Herein, we present recent progress of Janus particles, comprehensively detailing fabrication strategies and applications. First, the classification of JNPs is divided into three blocks, consisting of polymeric composites, inorganic composites, and hybrid polymeric/inorganic JNPs composites. Then, the fabrication strategies are alternately summarized, examining self-assembly strategy, phase separation strategy, seed-mediated polymerization, microfluidic preparation strategy, nucleation growth methods, and masking methods. Finally, various intriguing applications of JNPs are presented, including solid surfactants agents, micro/nanomotors, and biomedical applications such as biosensing, controlled drug delivery, bioimaging, cancer therapy, and combined theranostics. Furthermore, challenges and future works in this field are provided.
Asunto(s)
Nanopartículas Multifuncionales , Nanopartículas , Microfluídica , PolímerosRESUMEN
Biocompatible nano-antioxidants composed of natural molecules/materials, such as dopamine and melanin, are of great interest for diverse biomedical applications. However, the lack of understanding of the precise structure of these biomaterials and thus the actual dose of effective components impedes their advancement to translation. Herein, a strategy to mimic in situ melanin formation and explore its antioxidative applications is reported, by developing a PEGylated, phenylboronic-acid-protected L-DOPA precursor (PAD) that can self-assemble into well-defined nanoparticles (PADN). Exposure to oxidative species leads to deprotection of phenylboronic acids, transforming PADN to PEG-L-DOPA, which, similar to the biosynthetic pathway of melanin, can be oxidized and polymerized into an antioxidative melanin-like structure. With ultrahigh stability and superior antioxidative activity, the PADN shows remarkable efficacy in prevention and treatment of acute liver injury/failure. Moreover, the in situ structure transformation enables PADN to visualize damaged tissue noninvasively by photoacoustic imaging. Overall, a bioinspired antioxidant with precise structure and site-specific biological activity for theranostics of oxidative stress-related diseases is described.
Asunto(s)
Antioxidantes/química , Fallo Hepático Agudo/diagnóstico por imagen , Fallo Hepático Agudo/terapia , Melaninas/química , Animales , Apoptosis , Peróxido de Hidrógeno/química , Levodopa/química , Hígado , Fallo Hepático Agudo/metabolismo , Espectroscopía de Resonancia Magnética , Masculino , Potenciales de la Membrana , Ratones , Ratones Endogámicos BALB C , Microscopía Electrónica de Transmisión , Nanopartículas/química , Estrés Oxidativo , Oxígeno/química , Técnicas Fotoacústicas/métodos , Polietilenglicoles/química , Células RAW 264.7 , Especies Reactivas de Oxígeno , Nanomedicina Teranóstica , Resultado del TratamientoRESUMEN
Fluorescence (FL) and photoacoustic (PA) imaging in the second near infrared window (NIR-II FL and NIR-II PA) hold great promise for biomedical applications because of their non-invasive nature and excellent spatial resolution properties. Methods: We develop a NIR-II PA and NIR-II FL dual-mode imaging gold nanorod vesicles (AuNR Ves) by self-assembly of amphiphilic AuNR coated with light responsive polyprodrug of Ru-complex and PEG, and NIR-II cyanine dye (IR 1061). The AuNR Ves showed strong ligh absorption property and PA imaging performance in the NIR-II windows. Moreover, the NIR-II fluorescence signal of IR 1061 loaded in the AuNR Ve is quenched. Results: The AuNR Ves can release photosensitizer Ru-complex and IR 1061 sequentially triggered by NIR light irradiation, leading to a corresponding NIR-II PA signal decrease and NIR-II FL signal recovery. Meanwhile, Ru-complex can not only serve as a chemotherapeutic drug but also generate singlet oxygen (1O2) under NIR light irradiation. The release of Ru-complex and photodynamic therapy are guided by the responsive variation of NIR-II PA and NIR-II FL signals. Conclusions: The AuNR Ve possessing not only precisely control 1O2/drug release but also the intrinsic ability to monitor therapy process offers a new strategy for the development of smart theranostic nanoplatform.
Asunto(s)
Neoplasias de la Mama/terapia , Oro/química , Nanopartículas Multifuncionales/administración & dosificación , Nanotubos/química , Técnicas Fotoacústicas/métodos , Fármacos Fotosensibilizantes/farmacología , Nanomedicina Teranóstica/métodos , Animales , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Femenino , Fluorescencia , Humanos , Rayos Infrarrojos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Nanopartículas Multifuncionales/química , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/química , Polietilenglicoles/química , Medicina de Precisión , Rubidio/química , Oxígeno Singlete , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Rationale: Photothermal therapy (PTT) alone is easy to cause cancer recurrence and fail to completely resist metastasis, yet recurrence and metastasis are two major difficulties in cancer treatment. Titanium disulfide (TiS2) nanosheet anchored iron oxide nanoparticles (IO NPs) with strong absorption in the second near-infrared (NIR-II) window and excellent magnetic properties is developed as therapeutic agent for NIR-II photoacoustic (PA) imaging and magnetic resonance (MR) imaging guided NIR-II PTT triggered immunotherapy. Methods: The TiS2 nanosheets were prepared through a modified colloidal chemistry approach, and TSIO nanoagents were prepared by using a one pot self-assembly technique. The magnetic targeting capability of TSIO nanoagents were monitored by NIR-II PA, MR and thermal imaging in vivo. The NIR-II PTT combined with immunotherapy effect was investigated in mouse breast cancer tumor-bearing mice. Results: The TSIO nanoplatform showed enhanced tumor accumulation when a magnetic field was applied and had the ability to real time monitor the treatment process via dual NIR-II PA and MR imaging. In addition, the magnetic targeted NIR-II PA/MR imaging guided PTT provides an effective way to reverse the immunosuppression inside a tumor and to cooperate with immunotherapy to improve therapeutic outcome of the primary, distal and metastatic tumors.
Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/terapia , Inmunoterapia/métodos , Nanopartículas/administración & dosificación , Terapia Fototérmica/métodos , Radioterapia Guiada por Imagen/métodos , Titanio/química , Animales , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/patología , Línea Celular Tumoral , Modelos Animales de Enfermedad , Femenino , Imagen por Resonancia Magnética/métodos , Ratones , Ratones Endogámicos BALB C , Nanopartículas/química , Polímeros/química , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/inmunologíaRESUMEN
We developed dual biologically responsive nanogapped gold nanoparticle vesicles loaded with immune inhibitor and carrying an anticancer polymeric prodrug for synergistic concurrent chemo-immunotherapy against primary and metastatic tumors, along with guided cargo release by photoacoustic (PA) imaging in the second near-infrared (NIR-II) window. The responsive vesicle was prepared by self-assembly of nanogapped gold nanoparticles (AuNNPs) grafted with poly(ethylene glycol) (PEG) and dual pH/GSH-responsive polyprodug poly(SN38-co-4-vinylpyridine) (termed AuNNP@PEG/PSN38VP), showing intense PA signal in the NIR-II window. The effect of the rigidity of hydrophobic polymer PSN38VP on the assembled structures and the formation mechanism of AuNNP@SN38 Ve were elucidated by computational simulations. The immune inhibitor BLZ-945 was encapsulated into the vesicles, resulting in pH-responsive release of BLZ-945 for targeted immunotherapy, followed by the dissociation of the vesicles into single AuNNP@PEG/PSN38VP. The hydrophilic AuNNP@PEG/PSN38VP nanoparticles could penetrate deep into the tumor tissues and release the anticancer drug SN38 under the reductive environment. A PA signal in the NIR-II window in the deep tumor region was obtained. The BLZ-945-loaded vesicle enabled enhanced PA imaging-guided concurrent chemo-immunotherapy efficacy, inhibiting the growth of both primary tumors and metastatic tumors.
Asunto(s)
Nanopartículas del Metal , Nanopartículas , Técnicas Fotoacústicas , Oro , Inmunoterapia , PolímerosRESUMEN
Immunogenic cell death (ICD) and tumour-infiltrating T lymphocytes are severely weakened by elevated reactive oxygen species (ROS) in the tumour microenvironment. It is therefore of critical importance to modulate the level of extracellular ROS for the reversal of immunosuppressive environment. Here, we present a tumour extracellular matrix (ECM) targeting ROS nanoscavenger masked by pH sensitive covalently crosslinked polyethylene glycol. The nanoscavenger anchors on the ECM to sweep away the ROS from tumour microenvironment to relieve the immunosuppressive ICD elicited by specific chemotherapy and prolong the survival of T cells for personalized cancer immunotherapy. In a breast cancer model, elimination of the ROS in tumour microenvironment elicited antitumour immunity and increased infiltration of T lymphocytes, resulting in highly potent antitumour effect. The study highlights a strategy to enhance the efficacy of cancer immunotherapy by scavenging extracellular ROS using advanced nanomaterials.
Asunto(s)
Antineoplásicos/farmacología , Espacio Extracelular/metabolismo , Depuradores de Radicales Libres/metabolismo , Muerte Celular Inmunogénica , Especies Reactivas de Oxígeno/metabolismo , Animales , Línea Celular Tumoral , Células Dendríticas/efectos de los fármacos , Células Dendríticas/metabolismo , Proteína HMGB1/metabolismo , Muerte Celular Inmunogénica/efectos de los fármacos , Ratones Endogámicos BALB C , Tamaño de la Partícula , Polietilenglicoles/química , Microambiente Tumoral/efectos de los fármacosRESUMEN
Photoacoustic (PA) imaging as a fast-developing imaging technique has great potential in biomedical and clinical applications. It is a noninvasive imaging modality that depends on the light-absorption coefficient of the imaged tissue and the injected PA-imaging contrast agents. Furthermore, PA imaging provides superb contrast, super spatial resolution, and high penetrability and sensitivity to tissue functional characteristics by detecting the acoustic wave to construct PA images. In recent years, a series of PA-imaging contrast agents are developed to improve the PA-imaging performance in biomedical applications. Here, recent progress of PA contrast agents and their biomedical applications are outlined. PA contrast agents are classified according to their components and function, and gold nanocrystals, gold-nanocrystal assembly, transition-metal chalcogenides/MXene-based nanomaterials, carbon-based nanomaterials, other inorganic imaging agents, small organic molecules, semiconducting polymer nanoparticles, and nonlinear PA-imaging contrast agents are discussed. The applications of PA contrast agents as biosensors (in the sensing of metal ions, pH, enzymes, temperature, hypoxia, reactive oxygen species, and reactive nitrogen species) and in bioimaging (lymph nodes, vasculature, tumors, and brain tissue) are discussed in detail. Finally, an outlook on the future research and investigation of PA-imaging contrast agents and their significance in biomedical research is presented.
Asunto(s)
Medios de Contraste/química , Ganglios Linfáticos/diagnóstico por imagen , Neoplasias/diagnóstico por imagen , Imagen Óptica/métodos , Técnicas Fotoacústicas/métodos , Animales , Técnicas Biosensibles/métodos , Carbono/química , Línea Celular Tumoral , Complejos de Coordinación/química , Humanos , Nanopartículas del Metal/química , Polímeros/química , SemiconductoresRESUMEN
Injectable in situ thermosensitive hydrogels have potential applications in tissue engineering and drug delivery. The hydrogel formulations exist as aqueous solutions at room temperature but rapidly solidify into gels at 37⯰C in situ, making them highly suitable for administering drugs in a minimally invasive manner to the target organ(s). The hydrogel formed with nanoparticles assembled with amphiphilic polymer blocks of polyethyleneglycol (PEG) and biodegradable polycaprolactone (PCL) have been tested as platforms for targeted and sustained drug delivery, and have shown encouraging results. In this review, we summarize the influence of the molecular weight, PEG/PCL ratio and functional structure of hydrophobic PCL blocks on the critical gelation temperature, gelling behavior and drug release kinetics of the hydrogels. The current studies on the biomedical applications of thermosensitive PEG/PCL hydrogels have also been discussed.
Asunto(s)
Materiales Biocompatibles/química , Hidrogeles/química , Nanocápsulas/química , Poliésteres/química , Polietilenglicoles/química , Animales , Materiales Biocompatibles/administración & dosificación , Composición de Medicamentos , Liberación de Fármacos , Humanos , Hidrogeles/administración & dosificación , Interacciones Hidrofóbicas e Hidrofílicas , Cinética , Estructura Molecular , Peso Molecular , Nanocápsulas/administración & dosificación , Transición de Fase , Relación Estructura-Actividad , TemperaturaRESUMEN
In cancer treatment, surface modification by penetrating peptides and size control have been exploited as the two main strategies to tackle the problems of deep tumor penetration and cell internalization for nanocarriers. Polymeric nanocarriers with small size are beneficial for deep tumor penetration; however, they always undergo rapid clearance during body circulation and have low tumor accumulation efficiency. To solve this dilemma, a tumor-targeted size-switchable CPT/IR780@H30-PCL-PPI(L-)/PEI(-COOH/FA) nanoassembly with a "pomegranate" construction was designed in this study. Initially, it possessed a large size and negative charge to meet the long blood circulation time but rapidly disassembled into small-sized guanidinium and helical chain-modified unimolecular micelle-based nanocarriers, CPT/IR780@H30-PCL-PPI(L-/ + ), at tumor sites due to the tumor microenvironment-induced charge reversal. The CPT/IR780@H30-PCL-PPI(L-/+) assembly could efficiently expand the penetration depth and accelerate cell internalization due to the guanidinium group-modified helical chains, which exhibited a similar structure to that of the cell penetrating peptides. In addition, the nanoassembly exhibited strong photothermal conversion and acoustic generation efficiency. Moreover, the generated heat significantly improved the drug release, thus realizing functional cooperativity and adaptability. This proof of concept can be supposed to be a significant progress in the design and preparation of tumor microenvironment-responsive drug delivery systems and their use for photoacoustic imaging-assisted chemo-photothermal synergistic therapy.
Asunto(s)
Portadores de Fármacos/química , Nanoestructuras/química , Técnicas Fotoacústicas , Fototerapia , Animales , Camptotecina/química , Camptotecina/farmacología , Ratones , Micelas , Poliésteres/química , Polietileneimina/químicaRESUMEN
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.