RESUMO
Neurotransmitter receptors are increasingly recognized to play important roles in anti-tumor immunity. The expression of the ion channel N-methyl-D-aspartate receptor (NMDAR) on macrophages was reported, but the role of NMDAR on macrophages in the tumor microenvironment (TME) remains unknown. Here, we show that the activation of NMDAR triggered calcium influx and reactive oxygen species production, which fueled immunosuppressive activities in tumor-associated macrophages (TAMs) in the hepatocellular sarcoma and fibrosarcoma tumor settings. NMDAR antagonists, MK-801, memantine, and magnesium, effectively suppressed these processes in TAMs. Single-cell RNA sequencing analysis revealed that blocking NMDAR functionally and metabolically altered TAM phenotypes, such that they could better promote T cell- and Natural killer (NK) cell-mediated anti-tumor immunity. Treatment with NMDAR antagonists in combination with anti-PD-1 antibody led to the elimination of the majority of established preclinical liver tumors. Thus, our study uncovered an unknown role for NMDAR in regulating macrophages in the TME of hepatocellular sarcoma and provided a rationale for targeting NMDAR for tumor immunotherapy.
Assuntos
Neoplasias Hepáticas , Sarcoma , Humanos , Macrófagos Associados a Tumor , Processos Neoplásicos , Memantina , Microambiente TumoralRESUMO
Insufficient drug loading and leakage of payload remain major challenges in designing liposome-based drug delivery systems. These phenomena can limit duration of effect and cause toxicity. Targeting the rate-limiting step in drug release from liposomes, we modify (aromatized) them to have aromatic groups within their lipid bilayers. Aromatized liposomes are designed with synthetic phospholipids with aromatic groups covalently conjugated onto acyl chains. The optimized aromatized liposome increases drug loading and significantly decreases the burst release of a broad range of payloads (small molecules and macromolecules, different degrees of hydrophilicity) and extends their duration of release. Aromatized liposomes encapsulating the anesthetic tetrodotoxin (TTX) achieve markedly prolonged effect and decreased toxicity in an application where liposomes are used clinically: local anesthesia, even though TTX is a hydrophilic small molecule which is typically difficult to encapsulate. Aromatization of lipid bilayers can improve the performance of liposomal drug delivery systems.
Assuntos
Bicamadas Lipídicas , Lipossomos , Sistemas de Liberação de Medicamentos , Fosfolipídeos , Liberação Controlada de FármacosRESUMO
Delivery of hydrophilic small molecule therapeutics by traditional drug delivery systems is challenging. Herein, we have used the specific interaction between DNA aptamers and drugs to create simple and effective drug depot systems. The specific binding of a phosphorothioate-modified aptamer to drugs formed non-covalent aptamer/drug complexes, which created a sustained release system. We demonstrated the effectiveness of this system with small hydrophilic molecules, the site 1 sodium channel blockers tetrodotoxin and saxitoxin. The aptamer-based delivery system greatly prolonged the duration of local anesthesia and reduced systemic toxicity. The beneficial effects of the aptamers were restricted to the compounds they were specific to. These studies establish aptamers as a class of highly specific, modifiable drug delivery systems, and demonstrate potential usefulness in the management of postoperative pain.
Assuntos
Aptâmeros de Nucleotídeos , Sistemas de Liberação de Medicamentos , Preparações de Ação Retardada , Aptâmeros de Nucleotídeos/química , Tetrodotoxina/farmacologia , Bloqueadores dos Canais de SódioRESUMO
Site-1 sodium channel blockers (S1SCBs) act as potent local anaesthetics, but they can cause severe systemic toxicity. Delivery systems can be used to reduce the toxicity, but the hydrophilicity of S1SCBs makes their encapsulation challenging. Here, we report a self-assembling delivery system for S1SCBs whose design is inspired by the specific interactions of S1SCBs with two peptide sequences on the sodium channel. Specifically, the peptides were modified with hydrophobic domains so that they could assemble into nanofibres that facilitated specific binding with the S1SCBs tetrodotoxin, saxitoxin and dicarbamoyl saxitoxin. Injection of S1SCB-carrying nanofibres at the sciatic nerves of rats led to prolonged nerve blockade and to reduced systemic toxicity, with benign local-tissue reaction. The strategy of mimicking a molecular binding site via supramolecular interactions may be applicable more broadly to the design of drug delivery systems for receptor-mediated drugs.
Assuntos
Anestésicos Locais , Bloqueio Nervoso , Animais , Ratos , Ratos Sprague-Dawley , Canais de Sódio , TetrodotoxinaRESUMO
Ultrasound (US)-triggered sonodynamic therapy (SDT), as a promising noninvasive therapeutic modality, has received ever-increasing attention in recent years. Its specialized chemical agents, named sonosensitizers, are activated by low-intensity US to produce lethal reactive oxygen species (ROS) for oncotherapy. Compared with phototherapeutic strategies, SDT provides many noteworthy opportunities and benefits, such as deeper penetration depth, absence of phototoxicity, and fewer side effects. Nevertheless, previous studies have also demonstrated its intrinsic limitations. Thanks to the facile engineering nature of nanotechnology, numerous novel nanoplatforms are being applied in this emerging field to tackle these intrinsic barriers and achieve continuous innovations. In particular, the combination of SDT with other treatment strategies has demonstrated a superior efficacy in improving anticancer activity relative to that of monotherapies alone. Therefore, it is necessary to summarize the nanomaterial-assisted combinational sonodynamic cancer therapy applications. Herein, the design principles in achieving synergistic therapeutic effects based on nanomaterial engineering methods are highlighted. The ultimate goals are to stimulate the design of better-quality combined sonodynamic treatment schemes and provide innovative ideas for the perspectives of SDT in promoting its future transformation to clinical application.
Assuntos
Nanomedicina/métodos , Nanoestruturas/uso terapêutico , Neoplasias/terapia , Terapia por Ultrassom , Animais , Terapia Combinada , HumanosRESUMO
Existing tissue adhesives have a trade-off between adhesive strength and biocompatibility. Here, we report a series of biocompatible multiarmed polycaprolactones (PCL) as tissue adhesives that can be released from a hot glue gun and the length of each arm was kept at â¼2-3 kg mol-1 in all the polymers. The adhesion properties were dependent on the number of functionalized (N-hydroxysuccinimide ester (NHS), aldehyde (CHO), and isocyanate (NCO)) arms of the multiarmed polymers. The more arms, the higher the adhesion strength. For example, the adhesion strength in binding cut rat skin increased from 2.3 N cm-2 for 2PCL-NHS to 11.2 N cm-2 for 8-PCL-NHS. CHO- and NCO-modified 8PCL also had suitable adhesive properties. All the multiarmed polymers had minimal cytotoxicity in vitro and good biocompatibility in vivo, suggesting their potential as promising alternative surgical adhesives.
Assuntos
Materiais Biocompatíveis/química , Poliésteres/química , Adesivos Teciduais/química , Células 3T3 , Animais , Materiais Biocompatíveis/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Camundongos , Ratos , Ratos Sprague-Dawley , Pele/patologia , Adesivos Teciduais/farmacologia , Cicatrização/efeitos dos fármacosRESUMO
To date, the limited light conversion ability and the oxygen-dependent therapeutic process of most photosensitizers make it difficult to achieve satisfactory therapeutic effects in the complex tumor microenvironment, especially the anoxic environment. Herein, the black mesoporous titania (BMT) with large pore size (â¼8 nm) is synthesized as a new-style carrier for radical generator drug (AIBI) loading. The BMT as a light transducer can convert near-infrared (NIR) light energy into thermal energy and chemical energy (â¢OH), contributing to photothermal therapy (PTT) and photodynamic therapy (PDT), respectively. More importantly, AIBI would be thermally decomposed into alkyl radicals (â¢R) for thermodynamic therapy (TDT). The high concentration of free radicals produced by BMT@AIBI NCs resulted in double-strand breaks (DSBs) of DNA and finally induced cancer cell apoptosis. Since the generation of radicals is unrelated to oxygen, the BMT@AIBI NCs with NIR irradiation presented excellent in vitro and in vivo anticancer results under hypoxic conditions. The reported NIR-induced platform based on BMT@AIBI NCs, which could perform triple energy-conversion processes including light energy to thermal energy, to chemical energy, and to thermal energy then to chemical energy, realizes synergetic photo-thermal-dynamic therapy (PTT, PDT, and TDT) to overcome the problem of tumor hypoxia for enhanced anticancer effects.
Assuntos
Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Titânio/química , Animais , Quebras de DNA de Cadeia Dupla , Humanos , Hipertermia Induzida/métodos , Fototerapia/métodosRESUMO
Light-sensitive yolk-shell nanoparticles (YSNs) as remote-controlled and stimuli-responsive theranostic platforms provide an attractive method for synergistic cancer therapy. Herein, a kind of novel stimuli-responsive multifunctional YSNs has been successfully constructed by integrating star-shaped gold (Au star) nanoparticles as the second near-infrared (NIR-II) photothermal yolks and biodegradable crystalline zeolitic imidazolate framework-8 (ZIF-8) as the shells. In this platform, a chemotherapeutic drug (doxorubicin hydrochloride, DOX) was encapsulated into the cavity, which can show the behavior of controlled release due to the degradation process of ZIF-8 in the mildly acidic tumor microenvironment. Upon the 1064 nm (NIR-II biowindow) laser irradiation, gold nanostar@ZIF-8 (Au@MOF) nanoparticles exhibited outstanding synergistic anticancer effect based on their photothermal and promoted cargo release properties. Moreover, the strong NIR region absorbance endows the Au@MOF of NIR thermal imaging and photoacoustic (PA) imaging properties. This work contributes to design a stimuli-responsive "all-in-one" nanocarrier that realizes bimodal imaging diagnosis and chemo-photothermal synergistic therapy.
Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Doxorrubicina/uso terapêutico , Ouro/uso terapêutico , Estruturas Metalorgânicas/uso terapêutico , Nanopartículas/uso terapêutico , Neoplasias/terapia , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacocinética , Preparações de Ação Retardada/química , Preparações de Ação Retardada/uso terapêutico , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacocinética , Ouro/química , Células HeLa , Humanos , Hipertermia Induzida/métodos , Estruturas Metalorgânicas/química , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/química , Nanopartículas/ultraestrutura , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Técnicas Fotoacústicas , Nanomedicina TeranósticaRESUMO
As a noninvasive treatment modality, ultrasound (US)-triggered sonodynamic therapy (SDT) shows broad and promising applications to overcome the drawbacks of traditional photodynamic therapy (PDT) in combating cancer. However, the SDT efficacy is still not satisfactory without oxygen (O2) assistance. In addition, there is also much space to explore the SDT-based synergistic therapeutic modalities. Herein, a novel Pt-CuS Janus composed of hollow semiconductor CuS and noble metallic Pt was rationally designed and successfully synthesized. The hollow CuS shows a large inner cavity for loading sonosensitizer molecules (tetra-(4-aminophenyl) porphyrin, TAPP) to implement SDT. Moreover, the deposition of Pt not only enhances photothermal performance compared with those of CuS nanoparticles (NPs) due to the effect of the local electric field enhancement but also possesses nanozyme activity for catalyzing decomposition of endogenous overexpressed hydrogen peroxide (H2O2) to produce O2 that can overcome tumor hypoxia and augment the SDT-induced highly toxic reactive oxygen species (ROS) production for efficient cancer cell apoptosis. Importantly, the generated heat of Pt-CuS by 808 nm laser irradiation can accelerate the catalytic activity of Pt and elevate the O2 level that further facilitates SDT efficacy. Interestingly, the thermally sensitive copolymer coated around the Janus can act as a smart switch to regulate the catalytic ability of Pt and control TAPP release that has a significant effect on modulating the therapeutic effect. The synergistic catalysis-enhanced SDT efficiency and highly photothermal effect almost realized complete tumor resection without obvious reoccurrence and simultaneously displayed a highly therapeutic biosafety. Furthermore, the high optical absorbance allows the as-synthesized Pt-CuS Janus for photoacoustic (PA) imaging and NIR thermal imaging. This work develops a versatile nanoplatform for a multifunctional theranostic strategy and broadens the biological applications by rationally designing their structure.
Assuntos
Neoplasias do Colo/terapia , Cobre/uso terapêutico , Nanopartículas/uso terapêutico , Platina/uso terapêutico , Animais , Linhagem Celular Tumoral , Humanos , Hipertermia Induzida , Camundongos , Nanopartículas/ultraestrutura , Hipóxia Tumoral , Terapia por UltrassomRESUMO
We report sub-100â¯nm metal-shell (Au) dielectric-core (BaTiO3) nanoparticles with bimodal imaging abilities and enhanced photothermal effects. The nanoparticles efficiently absorb light in the near infrared range of the spectrum and convert it to heat to ablate tumors. Their BaTiO3 core, a highly ordered non-centrosymmetric material, can be imaged by second harmonic generation, and their Au shell generates two-photon luminescence. The intrinsic dual imaging capability allows investigating the distribution of the nanoparticles in relation to the tumor vasculature morphology during photothermal ablation. Our design enabled in vivo real-time tracking of the BT-Au-NPs and observation of their thermally-induced effect on tumor vessels. STATEMENT OF SIGNIFICANCE: Photothermal therapy induced by plasmonic nanoparticles has emerged as a promising approach to treating cancer. However, the study of the role of intratumoral nanoparticle distribution in mediating tumoricidal activity has been hampered by the lack of suitable imaging techniques. This work describes metal-shell (Au) dielectric-core (BaTiO3) nanoparticles (abbreviated as BT-Au-NP) for photothermal therapy and bimodal imaging. We demonstrated that sub-100â¯nm BT-Au-NP can efficiently absorb near infrared light and convert it to heat to ablate tumors. The intrinsic dual imaging capability allowed us to investigate the distribution of the nanoparticles in relation to the tumor vasculature morphology during photothermal ablation, enabling in vivo real-time tracking of the BT-Au-NPs and observation of their thermally-induced effect on tumor vessels.
Assuntos
Adenocarcinoma/terapia , Compostos de Bário , Ouro , Hipertermia Induzida , Neoplasias Mamárias Experimentais/terapia , Nanopartículas , Fototerapia , Titânio , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Animais , Compostos de Bário/química , Compostos de Bário/farmacocinética , Compostos de Bário/farmacologia , Linhagem Celular Tumoral , Feminino , Ouro/química , Ouro/farmacocinética , Ouro/farmacologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Nus , Nanopartículas/química , Nanopartículas/uso terapêutico , Titânio/química , Titânio/farmacocinética , Titânio/farmacologiaRESUMO
Titanium dioxide (TiO2 ) has been widely investigated and used in many areas due to its high refractive index and ultraviolet light absorption, but the lack of absorption in the visible-near infrared (Vis-NIR) region limits its application. Herein, multifunctional Fe@γ-Fe2 O3 @H-TiO2 nanocomposites (NCs) with multilayer-structure are synthesized by one-step hydrogen reduction, which show remarkably improved magnetic and photoconversion effects as a promising generalists for photocatalysis, bioimaging, and photothermal therapy (PTT). Hydrogenation is used to turn white TiO2 in to hydrogenated TiO2 (H-TiO2 ), thus improving the absorption in the Vis-NIR region. Based on the excellent solar-driven photocatalytic activities of the H-TiO2 shell, the Fe@γ-Fe2 O3 magnetic core is introduced to make it convenient for separating and recovering the catalytic agents. More importantly, Fe@γ-Fe2 O3 @H-TiO2 NCs show enhanced photothermal conversion efficiency due to more circuit loops for electron transitions between H-TiO2 and γ-Fe2 O3 , and the electronic structures of Fe@γ-Fe2 O3 @H-TiO2 NCs are calculated using the Vienna ab initio simulation package based on the density functional theory to account for the results. The reported core-shell NCs can serve as an NIR-responsive photothermal agent for magnetic-targeted photothermal therapy and as a multimodal imaging probe for cancer including infrared photothermal imaging, magnetic resonance imaging, and photoacoustic imaging.
Assuntos
Nanocompostos , Compostos Férricos , Humanos , Magnetismo , Neoplasias , TitânioRESUMO
Resistance to platinum agents is challenging in cancer treatment with platinum drugs. Such resistant cells prevent effective platinum accumulation intracellular and alter cellular adaptations to survive from cytotoxicity by regulating corresponding proteins expression. Ideal therapeutics should combine resolution to these pump and non-pump relevant resistance of cancer cells to achieve high efficacy and low side effect. Fe3O4 nanocarrier loaded with drugs could enter cells in a more efficient endocytosis manner which circumvents pump-relevant drug resistance. EZH2 protein which was previously found to be over-expressed in drug-resistant cancer cells was reported to be involved in platinum drug resistance and play a vital role in anti-apoptosis pathways. Here, we report Fe3O4 nanoparticles loaded with siEZH2 (siRNA), a platinum prodrug in +4 oxidation state (cis, cis, trans-diamminedichlorodisuccinato-platinum-(IV), namely Pt(IV)) and luteinizing hormone-releasing hormone (LHRH) targeting polypeptides. Results show that targeted nanoparticles loading with siEZH2 synergize with Pt(IV) and result in similar cell killing performance to A2780/DDP cells (cisplatin resistant) compared with non-siEZH2 loaded nanoparticles to A2780 cells (cisplatin sensitive). Thus, this Fe3O4@PEI-Pt(IV)-PEG-LHRH@siEZH2 nanoparticles reverse the cisplatin resistance from the pump and non-pump relevant aspects, fully taking advantage of nanocarrier system.
Assuntos
Ferro/química , Nanopartículas/química , Compostos Organoplatínicos/química , Platina/química , Pró-Fármacos/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Cisplatino/química , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Humanos , RNA Interferente PequenoRESUMO
Photothermal therapy (PTT) has attracted considerable attention in cancer treatment. Herein, the facile synthesis of copper iron sulfide (chalcopyrite, CuFeS2) nanoplates (NPs) with well-defined shape was achieved by a template-mediated method. Chitosan (CS), a linear cationic polysaccharide, was used to improve the physiological stability and biocompatibility. CuFeS2 NPs with strong near-infrared (NIR) absorbance enabled contrasts in photothermal and photoacoustic (PA) imaging. In vitro and in vivo tumor ablation studies further demonstrated that CS-functionalized CuFeS2 (CuFeS2-CS) NPs could convert 808 nm NIR light into heat for PTT with a photothermal conversion efficiency up to 30.5%, which was clearly higher than that of CuS NPs (only 21.4%). Furthermore, CuFeS2-CS NPs could also load cis-platinum pro-drug (CuFeS2-CS-Pt), and CuFeS2-CS-Pt showed a better synergistic therapeutic effect with respect to either chemotherapy or PTT.
Assuntos
Cisplatino/administração & dosagem , Nanoestruturas/química , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Pró-Fármacos/administração & dosagem , Células A549 , Animais , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Técnicas Fotoacústicas , FototerapiaRESUMO
Oleic acid (OA) and/or oleylamine (OAm) are generally used as the surface ligands for stabilization of inorganic nanocrystals (NCs). The hydrophobic and inert surface of the NCs limits their applications such as in biomedical areas. Hence, surface modifications are essential in many physical and chemical processes. Here, a facile and versatile strategy is reported for the modification of NCs by ultraviolet-induced thiol-ene chemistry, in which thiol-terminated poly(ethylene glycol) (HSPEG) and its derivatives can react directly with double bonds in OA/OAm ligands to form covalent linking within one step. Through this strategy, various hydrophobic NCs with different compositions and morphologies are able to be transferred into water combining with functionalization of active groups. As a proof-of-concept, this strategy is successfully used to construct a sensor for detecting avidin based on upconverting luminescence analysis. Therefore, this strategy provides a new tool for designing and tuning the surface properties of NCs for different applications.
RESUMO
Photoinduced reversible addition-fragmentation chain transfer (RAFT) polymerization generally adopts high-energy ultraviolet (UV) or blue light. In combination with photoredox catalyst, the excitation light wavelength was extended to the visible and even near-infrared (NIR) region for photoinduced electron transfer RAFT polymerization. In this report, we introduce for the first time a surface NIR-light-initiated RAFT polymerization on upconversion nanoparticles (UCNPs) without adding any photocatalyst and construct a functional inorganic core/polymer shell nanohybrid for application in cancer theranostics. The multilayer core-shell UCNPs (NaYF4:Yb/Tm@NaYbF4:Gd@NaNdF4:Yb@NaYF4), with surface anchorings of chain transfer agents, can serve as efficient NIR-to-UV light transducers for initiating the RAFT polymerization. A hierarchical double block copolymer brush, consisting of poly(acrylic acid) (PAA) and poly(oligo(ethylene oxide)methacrylate-co-2-(2-methoxy-ethoxy)ethyl methacrylate) (PEG for short), was grafted from the surface in sequence. The targeting arginine-glycine-aspartic (RGD) peptide was modified at the end of the copolymer through the trithiolcarbonate end group. After loading of doxorubicin, the UCNPs@PAA-b-PEG-RGD exhibited an enhanced U87MG cancer cell uptake efficiency and cytotoxicity. Besides, the unique upconversion luminescence of the nanohybrids was used for the autofluoresence-free cell imaging and labeling. Therefore, our strategy verified that UCNPs could efficiently activate RAFT polymerization by NIR photoirradiation and construct the complex nanohybrids, exhibiting prospective biomedical applications due to the low phototoxicity and deep penetration of NIR light.
Assuntos
Nanopartículas , Doxorrubicina , Polimerização , Polímeros , Estudos ProspectivosRESUMO
Elaborately designed biocompatible nanoplatforms simultaneously achieving multimodal bioimaging and therapeutic functions are highly desirable for modern biomedical applications. Herein, uniform MoS2 nanoflowers with a broad size range of 80-180 nm have been synthesized through a facile, controllable, and scalable hydrothermal method. The strong absorbance of MoS2 nanoflowers at 808 nm imparts them with high efficiency and stability of photothermal conversion. Then a novel multifunctional composite of MoS2@Fe3O4-ICG/Pt(IV) (labeled as Mo@Fe-ICG/Pt) is designed by covalently grafting Fe3O4 nanoparticles with polyethylenimine (PEI) functionalized MoS2, and then loading indocyanine green molecules (ICG, photosensitizers) and platinum (IV) prodrugs (labeled as Pt(IV) prodrugs) on the surface of MoS2@Fe3O4. The resulting Mo@Fe-ICG/Pt nanocomposites can achieve excellent magnetic resonance/infrared thermal/photoacoustic trimodal biomaging as well as remarkably enhanced antitumor efficacy of combined photothermal therapy, photodynamic therapy, and chemotherapy triggered by a single 808 nm NIR laser, thus leading to an ideal nanoplatform for cancer diagnosis and treatment in future.
RESUMO
It is of great importance in drug delivery to fabricate multifunctional nanocarriers with intelligent targeting properties, for cancer diagnosis and therapy. Herein, hollow-structured CuS@Cu2 S@Au nanoshell/satellite nanoparticles are designed and synthesized for enhanced photothermal therapy and photoswitchable targeting theranostics. The remarkably improved photothermal conversion efficiency of CuS@Cu2 S@Au under 808 nm near-infrared (NIR) laser irradiation can be explained by the reduced bandgap and more circuit paths for electron transitions for CuS and Cu2 S modified with Au nanoparticles, as calculated by the Vienna ab initio simulation package, based on density functional theory. By modification of thermal-isomerization RGD targeting molecules and thermally sensitive copolymer on the surface of nanoparticles, the transition of the shielded/unshielded mode of RGD (Arg-Gly-Asp) targeting molecules and shrinking of the thermally sensitive polymer by NIR photoactivation can realize a photoswitchable targeting effect. After loading an anticancer drug doxorubicin in the cavity of CuS@Cu2 S@Au, the antitumor therapy efficacy is greatly enhanced by combining chemo- and photothermal therapy. The reported nanohybrid can also act as a photoacoustic imaging agent and an NIR thermal imaging agent for real-time imaging, which provides a versatile platform for multifunctional theranostics and stimuli-responsive targeted cancer therapy.
Assuntos
Nanoestruturas , Cobre , Doxorrubicina , Ouro , Humanos , Neoplasias , Nanomedicina TeranósticaRESUMO
Size- and shape-controlled growth of nanoscale microporous organic polymers (MOPs) is a big challenge scientists are confronted with; meanwhile, rendering these materials for in vivo biomedical applications is still scarce. In this study, a monodispersed nanometalated covalent organic polymer (MCOP, M=Fe, Gd) with sizes around 120â nm was prepared by a self-templated two-step solution-phase synthesis method. The metal ions (Fe3+ , Gd3+ ) played important roles in generating a small particle size and in the functionalization of the products during the reaction with p-phenylenediamine (Pa). The resultant Fe-Pa complex was used as a template for the subsequent formation of MCOP following the Schiff base reaction with 1,3,5-triformylphloroglucinol (Tp). A high tumor suppression efficiency for this Pa-based COP is reported for the first time. This study demonstrates the potential use of MCOP as a photothermal agent for photothermal therapy (PTT) and also provides an alternative route to fabricate nano-sized MCOPs.
Assuntos
Imageamento por Ressonância Magnética , Nanoestruturas/química , Compostos Organometálicos/farmacologia , Fototerapia , Polímeros/farmacologia , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Neoplasias Hepáticas Experimentais/patologia , Camundongos , Nanoestruturas/administração & dosagem , Compostos Organometálicos/administração & dosagem , Compostos Organometálicos/química , Tamanho da Partícula , Polímeros/administração & dosagem , Polímeros/química , Porosidade , Relação Estrutura-Atividade , Propriedades de SuperfícieRESUMO
Anticancer drug doxorubicin hydrochloride (DOX)-loaded photothermal nanocomposite MnFe2O4@mSiO2 with magnetic targeting and T1/T2-weighted dual-mode magnetic resonance imaging of MnFe2O4 core and NIR/pH-coupling sensitive mesoporous silica shell nanocarriers was designed and synthesized successfully. The anticancer drug DOX can be absorbed into mesoporous layer of MnFe2O4@mSiO2 nanocomposite, which shows obvious photothermal/chemo dual-modal synergistic therapies triggered by NIR/pH. Under 808 nm irradiation, MnFe2O4 can transform light into thermo, which can not only ablate tumor cells directly but also promote chemotherapy drugs releasing from mesoporous layer to kill tumor cells. The lower pH can also promote DOX releasing from mesoporous layer to enhance tumor inhibitory effect. It is confirmed that biocompatible DOX-MnFe2O4@mSiO2 nanocomposites can act as a potential multifunctional platform for effective magnetic targeting photothermal/chemo dual-modal synergistic therapies with enhanced anti-tumor efficacy and T1/T2-weighted dual-mode magnetic resonance imaging (MRI) applications in vivo.
Assuntos
Antineoplásicos/administração & dosagem , Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Compostos Férricos/química , Imageamento por Ressonância Magnética/métodos , Compostos de Manganês/química , Nanocompostos/química , Neoplasias/terapia , Dióxido de Silício/química , Animais , Antineoplásicos/uso terapêutico , Terapia Combinada/métodos , Preparações de Ação Retardada/química , Preparações de Ação Retardada/uso terapêutico , Doxorrubicina/uso terapêutico , Compostos Férricos/uso terapêutico , Células HeLa , Humanos , Hipertermia Induzida/métodos , Campos Magnéticos , Compostos de Manganês/uso terapêutico , Camundongos , Nanocompostos/uso terapêutico , Nanocompostos/ultraestrutura , Neoplasias/diagnóstico por imagem , Fototerapia/métodos , Dióxido de Silício/uso terapêuticoRESUMO
The design of stimuli-responsive drug delivery systems has attracted much attention to improve therapeutic efficacy for clinical applications. Here an 808 nm NIR light responsive dual-drug system was designed for cancer treatment both in vitro and in vivo. Mesoporous silica coated NaYF4:Yb0.4/Tm0.02@NaGdF4:Yb0.1@NaNdF4:Yb0.1 (UCNPs) with a core-shell structure (labeled as UCNPs@mSiO2) was prepared and loaded with the antitumor drug doxorubicin (DOX). The surface of the composite was functionalized with ß-cyclodextrin rings bridged by the light cleavable platinum(iv) pro-drug, thus blocking DOX inside the mesopores of silica. When excited by 808 nm NIR light, the emitted UV light from the UCNPs was used to activate the platinum(iv) pro-drug to gain higher toxicity platinum(ii) complexes and open the mesopores of silica (at the same time) to release DOX molecules. Both DOX and platinum(ii) complexes can kill cancer cells. This dual-drug delivery system may represent a new avenue for the application of UCNPs in photoactivated cancer therapy.