RESUMEN
Cancer metastasis and recurrence are obstacles to successful treatment of aggressive cancer. To address this challenge, chemotherapy is indispensable as an essential part of comprehensive cancer treatment, particularly for subsequent therapy after surgical resection. However, small-molecule drugs for chemotherapy always cause inadequate efficacy and severe side effects against cancer metastasis and recurrence caused by lymph node metastases. Here, we developed doxorubicin-carried albumin nanocages (Dox-AlbCages) with appropriate particle sizes and pH/enzyme-responsive drug release for tumor and lymph node dual-targeted therapy by exploiting the inborn transport properties of serum albumin. Inspired by the protein-templated biomineralization and remote loading of doxorubicin into liposomes, we demonstrated the controlled synthesis of Dox-AlbCages via the aggregation or crystallization of doxorubicin and ammonium sulfate within albumin nanocages using a biomineralization strategy. Dox-AlbCages allowed efficient encapsulation of Dox in the core protected by the albumin corona shell, exhibiting favorable properties for enhanced tumor and lymph node accumulation and preferable cellular uptake for tumor-specific chemotherapy. Intriguingly, Dox-AlbCages effectively inhibited tumor growth and metastasis in orthotopic 4T1 breast tumors and prevented postsurgical tumor recurrence and lung metastasis. At the same time, Dox-AlbCages had fewer side effects than free Dox. This nanoplatform provides a facile strategy for designing tumor- and lymph node-targeted nanomedicines for suppressing cancer metastasis and recurrence.
Asunto(s)
Antibióticos Antineoplásicos , Doxorrubicina , Metástasis Linfática , Ratones Endogámicos BALB C , Doxorrubicina/administración & dosificación , Doxorrubicina/farmacocinética , Animales , Femenino , Línea Celular Tumoral , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/farmacocinética , Antibióticos Antineoplásicos/uso terapéutico , Liberación de Fármacos , Nanopartículas/administración & dosificación , Nanopartículas/química , Humanos , Ratones , Ganglios Linfáticos/patología , Ganglios Linfáticos/efectos de los fármacos , Ganglios Linfáticos/metabolismo , Sistemas de Liberación de Medicamentos , Albúminas/administración & dosificación , Albúminas/química , Portadores de Fármacos/químicaRESUMEN
INTRODUCTION: Arsenicals have a special place in the history of human health, acting both as poison and medicine. Having been used to treat a variety of diseases in the past, the success of arsenic trioxide (ATO) in treating acute promyelocytic leukemia (APL) in the last century marked its use as a drug in modern medicine. To expand their role against cancer, there have been clinical uses of arsenicals worldwide and progress in the development of drug delivery for various malignancies, especially solid tumors. AREAS COVERED: In this review, conducted on Google Scholar [1977-2024], we start with various forms of arsenicals, highlighting the well-known ATO. The mechanism of action of arsenicals in cancer therapy is then overviewed. A summary of the research progress in developing new delivery approaches (e.g. polymers, inorganic frameworks, and biomacromolecules) in recent years is provided, addressing the challenges and opportunities in treating various malignant tumors. EXPERT OPINION: Reducing toxicity and enhancing therapeutic efficacy are guidelines for designing and developing new arsenicals and drug delivery systems. They have shown potential in the fight against cancer and emerging pathogens. New technologies and strategies can help us harness the potency of arsenicals and make better products.
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Antineoplásicos , Trióxido de Arsénico , Arsenicales , Sistemas de Liberación de Medicamentos , Neoplasias , Humanos , Trióxido de Arsénico/administración & dosificación , Trióxido de Arsénico/uso terapéutico , Trióxido de Arsénico/farmacocinética , Neoplasias/tratamiento farmacológico , Arsenicales/administración & dosificación , Arsenicales/uso terapéutico , Arsenicales/farmacocinética , Antineoplásicos/administración & dosificación , Animales , Desarrollo de Medicamentos , Diseño de Fármacos , Leucemia Promielocítica Aguda/tratamiento farmacológicoRESUMEN
Hemorrhoidal disease (HEM) is a common condition affecting a significant proportion of the population. However, the causal relationship between the gut microbiota and hemorrhoids remains unclear. In this study, we employed a Mendelian randomization (MR) approach to investigate the potential associations between them. In this study, the exposure factor was determined by selecting summary statistics data from a large-scale gut microbiome whole-genome association study conducted by the MiBioGen Consortium, which involved a sample size of 18,340 individuals. The disease outcome data consisted of 218,920 cases of HEM and 725,213 controls of European ancestry obtained from the European Bioinformatics Institute dataset. Two-sample MR analyses were performed to assess the causalities between gut microbiota and hemorrhoids using various methods, including inverse-variance weighting, MR-Egger regression, MR Pleiotropy Residual Sum and Outlier (MR-PRESSO), simple mode, and weighted median. Reverse MR analyses were performed to examine reverse causal association. Our findings suggest phylum Cyanobacteria (ORâ =â 0.947, 95% CI: 0.915-0.980, Pâ =â 2.10â ×â 10â -â 3), genus Phascolarctobacterium (ORâ =â 0.960, 95% CI: 0.924-0.997, Pâ =â .034) and family FamilyXI (ORâ =â 0.974, 95% CI: 0.952-0.997, Pâ =â .027) have potentially protective causal effects on the risk of HEM, while genus Ruminococcaceae_UCG_002 (ORâ =â 1.036, 95% CI: 1.001-1.071, Pâ =â .042), family Peptostreptococcaceae (ORâ =â 1.042, 95% CI: 1.004-1.082, Pâ =â .029), genus Oscillospira (ORâ =â 1.048, 95% CI: 1.005-1.091, Pâ =â .026), family Alcaligenaceae (ORâ =â 1.048, 95% CI: 1.005-1.091, Pâ =â .036) and order Burkholderiales (ORâ =â 1.074, 95% CI: 1.020-1.130, Pâ =â 6.50â ×â 10-3) have opposite effect. However, there was a reverse causal relationship between HEM and genus Oscillospira (ORâ =â 1.140, 95% CI: 1.002-1.295, Pâ =â .046) This is the first MR study to explore the causalities between specific gut microbiota taxa and hemorrhoidal disease, which may offer valuable insights for future clinical interventions for hemorrhoidal disease.
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Microbioma Gastrointestinal , Hemorroides , Humanos , Hemorroides/genética , Microbioma Gastrointestinal/genética , Análisis de la Aleatorización Mendeliana , Academias e Institutos , Causalidad , Clostridiales , Estudio de Asociación del Genoma CompletoRESUMEN
Despite the continuous advancement of surgical resection techniques, postoperative tumor recurrence and metastasis remain a huge challenge. Here, we constructed an injectable curcumin/doxorubicin-loaded nanoparticle (NanoCD) hydrogel, which could effectively inhibit tumor regrowth and metastasis via reshaping the tumor immune microenvironment (TIME) for highly effective postsurgical cancer treatment. NanoCD was prepared by the controlled assembly of curcumin (CUR) and doxorubicin (DOX) via π-π stacking and hydrogen bonding in the presence of human serum albumin. To facilitate prolonged treatment of postsurgical tumors, NanoCD was further incorporated into the temperature-sensitive Poloxamer 407 gel (NanoCD@Gel) for intracavity administration. Mechanistically, DOX induced the generation of intracellular reactive oxygen species (ROS) and CUR reduced the ROS metabolism by inhibiting thioredoxin reductase (TrxR). The synergy of DOX and CUR amplified intracellular ROS levels and thus resulted in enhanced immunogenic cell death (ICD) of tumor cells. Upon being injected into the tumor cavity after resection, the in situ-generated NanoCD@Gel allowed the local release of CUR and DOX in a controlled manner to induce local chemotherapy and persistently activate the antitumor immune response, thereby achieving enhanced immunogenic chemotherapy with reduced systemic toxicity. Our work provides an elegant strategy for persistently stimulating effective antitumor immunity to prevent postsurgical tumor recurrence and metastasis.
Asunto(s)
Curcumina , Nanopartículas , Humanos , Curcumina/farmacología , Hidrogeles , Especies Reactivas de Oxígeno , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/prevención & control , Línea Celular Tumoral , Doxorrubicina , Microambiente TumoralRESUMEN
The survival of malignant tumors is highly dependent on their intrinsic self-defense pathways such as heat shock protein (HSP) during cancer therapy. However, precisely dismantling self-defenses to amplify antitumor potency remains unexplored. Herein, we demonstrate that nanoparticle-mediated transient receptor potential vanilloid member 1 (TRPV1) channel blockade potentiates thermo-immunotherapy via suppressing heat shock factor 1 (HSF1)-mediated dual self-defense pathways. TRPV1 blockade inhibits hyperthermia-induced calcium influx and subsequent nuclear translocation of HSF1, which selectively suppresses stressfully overexpressed HSP70 for enhancing thermotherapeutic efficacy against a variety of primary, metastatic and recurrent tumor models. Particularly, the suppression of HSF1 translocation further restrains the transforming growth factor ß (TGFß) pathway to degrade the tumor stroma, which improves the infiltration of antitumor therapeutics (e.g. anti-PD-L1 antibody) and immune cells into highly fibrotic and immunosuppressive pancreatic cancers. As a result, TRPV1 blockade retrieves thermo-immunotherapy with tumor-eradicable and immune memory effects. The nanoparticle-mediated TRPV1 blockade represents as an effective approach to dismantle self-defenses for potent cancer therapy.
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Antineoplásicos , Hipertermia Inducida , Canales de Potencial de Receptor Transitorio , Humanos , Recurrencia Local de Neoplasia , Respuesta al Choque Térmico , Inmunoterapia , Factores de Transcripción del Choque Térmico/genética , Canales Catiónicos TRPV/genéticaRESUMEN
Artificial enzymes have demonstrated therapeutic benefits against diverse malignant tumors, yet their antitumor potencies are still severely compromised by non-selective catalysis, low atomic-utilization efficiency, and undesired off-target toxicity. Herein, it is reported that peroxidase-like biomineralized copper (II) carbonate hydroxide nanocrystals inside single albumin nanocages (CuCH-NCs) act as a pH-activatable proenzyme to achieve tumor-selective and synergistic chemodynamic/chemo-immunotherapy against aggressive triple-negative breast cancers (TNBCs). These CuCH-NCs show pH-sensitive Cu2+ release, which spontaneously undergoes glutathione (GSH)-mediated reduction into Cu+ species for catalyzing the evolution of H2 O2 into hydroxyl radicals (·OH) in a single-atom-like manner to cause chemodynamic cell injury, and simultaneously activates non-toxic disulfiram to cytotoxic complex for yielding selective chemotherapeutic damage via blocking cell proliferation and amplifying cell apoptosis. CuCH-NCs exhibit considerable tumor-targeting capacity with deep penetration depth, thus affording preferable efficacy against orthotopic breast tumors through synergistic chemodynamic/chemotherapy, together with good in vivo safety. Moreover, CuCH-NCs arouse distinct immunogenic cell death effect and upregulate PD-L1 expression upon disulfiram combination, and thus synergize with anti-PD-L1 antibody to activate adaptive and innate immunities, together with relieving immunosuppression, finally yielding potent antitumor efficacy against both primary and metastatic TNBCs. These results provide insights into smart and high-performance proenzymes for synergistic therapy against aggressive cancers.
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Nanopartículas , Neoplasias , Humanos , Precursores Enzimáticos , Cobre , Disulfiram , Inmunoterapia , Glutatión , Concentración de Iones de Hidrógeno , Línea Celular Tumoral , Peróxido de Hidrógeno , Microambiente TumoralRESUMEN
Glutathione (GSH)-activatable probes hold great promise for in vivo cancer imaging, but are restricted by their dependence on non-selective intracellular GSH enrichment and uncontrollable background noise. Here, a holographically activatable nanoprobe caging manganese tetraoxide is shown for tumor-selective contrast enhancement in magnetic resonance imaging (MRI) through cooperative GSH/albumin-mediated cascade signal amplification in tumors and rapid elimination in normal tissues. Once targeting tumors, the endocytosed nanoprobe effectively senses the lysosomal microenvironment to undergo instantaneous decomposition into Mn2+ with threshold GSH concentration of ≈ 0.12 mm for brightening MRI signals, thus achieving high contrast tumor imaging and flexible monitoring of GSH-relevant cisplatin resistance during chemotherapy. Upon efficient up-regulation of extracellular GSH in tumor via exogenous injection, the relaxivity-silent interstitial nanoprobe remarkably evolves into Mn2+ that are further captured/retained and re-activated into ultrahigh-relaxivity-capable complex by stromal albumin in the tumor, and simultaneously allows the renal clearance of off-targeted nanoprobe in the form of Mn2+ via lymphatic vessels for suppressing background noise to distinguish tiny liver metastasis. These findings demonstrate the concept of holographic tumor activation via both tumor GSH/albumin-mediated cascade signal amplification and simultaneous background suppression for precise tumor malignancy detection, surveillance, and surgical guidance.
Asunto(s)
Albúminas , Glutatión , Imagen por Resonancia Magnética , Nanopartículas del Metal , Sondas Moleculares , Neoplasias , Glutatión/administración & dosificación , Glutatión/farmacocinética , Glutatión/farmacología , Sondas Moleculares/administración & dosificación , Sondas Moleculares/farmacocinética , Sondas Moleculares/farmacología , Albúminas/administración & dosificación , Albúminas/farmacocinética , Albúminas/farmacología , Imagen por Resonancia Magnética/métodos , Medios de Contraste/administración & dosificación , Medios de Contraste/farmacocinética , Medios de Contraste/farmacología , Aumento de la Imagen/métodos , Holografía/métodos , Neoplasias/diagnóstico por imagen , Neoplasias/metabolismo , Lisosomas/efectos de los fármacos , Lisosomas/metabolismo , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/fisiología , Nanopartículas del Metal/administración & dosificación , Transferrina/administración & dosificación , Transferrina/farmacocinética , Transferrina/farmacología , Distribución Tisular , Células A549 , Humanos , Animales , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Cisplatino/administración & dosificación , Cisplatino/farmacocinética , Cisplatino/farmacología , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologíaRESUMEN
Nano-drug delivery strategies have been highlighted in cancer treatment, and much effort has been made in the optimization of bioavailability, biocompatibility, pharmacokinetics profiles, and in vivo distributions of anticancer nano-drug delivery systems. However, problems still exist in the delicate balance between improved anticancer efficacy and reduced toxicity to normal tissues, and opportunities arise along with the development of smart stimuli-responsive delivery strategies. By on-demand responsiveness towards exogenous or endogenous stimulus, these smart delivery systems hold promise for advanced tumor-specificity as well as controllable release behavior in a spatial-temporal manner. Meanwhile, the blossom of nanotechnology, material sciences, and biomedical sciences has shed light on the diverse modern drug delivery systems with smart characteristics, versatile functions, and modification possibilities. This review summarizes the current progress in various strategies for smart drug delivery systems against malignancies and introduces the representative endogenous and exogenous stimuli-responsive smart delivery systems. It may provide references for researchers in the fields of drug delivery, biomaterials, and nanotechnology.
RESUMEN
Arsenotherapy has been clinically exploited to treat a few types of solid tumors despite of acute promyelocytic leukemia using arsenic trioxide (ATO), however, its efficacy is hampered by inadequate delivery of ATO into solid tumors owing to the absence of efficient and biodegradable vehicles. Precise spatiotemporal control of subcellular ATO delivery for potent arsenotherapy thus remains challengeable. Herein, we report the self-activated arsenic manganite nanohybrids for high-contrast magnetic resonance imaging (MRI) and arsenotherapeutic synergy on triple-negative breast cancer (TNBC). The nanohybrids, composed of arsenicmanganese-co-biomineralized nanoparticles inside albumin nanocages (As/Mn-NHs), switch signal-silent background to high proton relaxivity, and simultaneously afford remarkable subcellular ATO level in acidic and glutathione environments, together with reduced ATO resistance against tumor cells. Then, the nanohybrids enable in vivo high-contrast T1-weighted MRI signals in various tumor models for delineating tumor boundary, and simultaneously yield efficient arsenotherapeutic efficacy through multiple apoptotic pathways for potently suppressing subcutaneous and orthotopic breast models. As/Mn-NHs exhibited the maximum tumor-to-normal tissue (T/N) contrast ratio of 205% and tumor growth inhibition rate of 88% at subcutaneous 4T1 tumors. These nanohybrids further yield preferable synergistic antitumor efficacy against both primary and metastatic breast tumors upon combination with concurrent thermotherapy. More importantly, As/Mn-NHs considerably induce immunogenic cell death (ICD) effect to activate the immunogenically "cold" tumor microenvironment into "hot" one, thus synergizing with immune checkpoint blockade to yield the strongest tumor inhibition and negligible metastatic foci in the lung. Our study offers the insight into clinically potential arsenotherapeutic nanomedicine for potent therapy against solid tumors.
Asunto(s)
Antineoplásicos , Arsénico , Arsenicales , Neoplasias , Albúminas , Apoptosis , Arsénico/farmacología , Arsénico/uso terapéutico , Trióxido de Arsénico/farmacología , Trióxido de Arsénico/uso terapéutico , Arsenicales/uso terapéutico , Línea Celular Tumoral , Glutatión/farmacología , Humanos , Inhibidores de Puntos de Control Inmunológico , Manganeso , Compuestos de Manganeso , Neoplasias/tratamiento farmacológico , Óxidos , Protones , Microambiente TumoralRESUMEN
BACKGROUND: Myocardial damage and decreased ventricular function are risk factors leading to a bad prognosis in patients with essential hypertension (EH). MicroRNAs play important roles in myocardial function impairment in patients with hypertension. The purpose of our research was to investigate the correlation between serum miR-122 and myocardial damage and ventricular functions in EH patients. METHODS: The clinic data of EH patients (group A, n=60) and healthy individuals (group B, n=60) from December 2016 to December 2019 in our hospital were collected and analyzed. Serum miR-122, myocardial damage markers [B-type brain natriuretic peptide (BNP), homocysteine (Hcy), cardiac troponin T (cTnT) and creatine kinase MB isoenzyme (CK-MB)] and cardiac function indicators [ejection fraction (EF), left ventricular septal thickness (IVST), left ventricular isovolumic relaxation time (IVRT), left ventricular end-diastolic diameter (LVEDD), left ventricular posterior wall thickness (LVPWT), and left ventricular end-systolic diameter (LVESD)] were assessed in both groups. The correlation between serum miR-122 and myocardial damage markers and ventricular function indicators was analyzed. RESULTS: (I) The mean serum miR-122 concentration in group A and group B was 6.86±1.23 and 3.36±1.87 µmol/L, respectively. The serum miR-122 concentration in group A was evidently increased compared with that in group B. (II) The levels of BNP, Hcy, cTnT, and CK-MB in the peripheral blood in group A were evidently increased compared with those in group B (P<0.05). (III) EF and IVRT were evidently decreased in group A compared with that in group B (P<0.05). (IV) Serum miR-122 concentration was positively correlated with the myocardial damage markers BNP, Hcy, cTnT and CK-MB, and serum miR-122 concentration was negatively correlated with the ventricular function indicators EF and IVRT but not significantly correlated with other ventricular function indicators (IVST, LVEDD, LVPWT and LVESD). CONCLUSIONS: The serum miR-122 concentration in EH patients was higher than that in healthy individuals, and miR-122 concentration was positively correlated with myocardial damage markers. Serum miR-122 level was negatively correlated with the ventricular function indicators EF and IVRT but was not significantly correlated with other ventricular function indicators (IVST, LVEDD, LVPWT, and LVESD).
RESUMEN
Tumor tissues/cells are the best sources of antigens to prepare cancer vaccines. However, due to the difficulty of solubilization and delivery of water-insoluble antigens in tumor tissues/cells, including water-insoluble antigens into cancer vaccines and delivering such vaccines efficiently to antigen-presenting cells (APCs) remain challenging. To solve these problems, herein, water-insoluble components of tumor tissues/cells are solubilized by 8 m urea and thus whole components of micrometer-sized tumor cells are reasssembled into nanosized nanovaccines. To induce maximized immunization efficacy, various antigens are loaded both inside and on the surface of nanovaccines. By encapsulating both water-insoluble and water-soluble components of tumor tissues/cells into nanovaccines, the nanovaccines are efficiently phagocytosed by APCs and showed better therapeutic efficacy than the nanovaccine loaded with only water-soluble components in melanoma and breast cancer. Anti-PD-1 antibody and metformin can improve the efficacy of nanovaccines. In addition, the nanovaccines can prevent lung cancer (100%) and melanoma (70%) efficiently in mice. T cell analysis and tumor microenvironment analysis indicate that tumor-specific T cells are induced by nanovaccines and both adaptive and innate immune responses against cancer cells are activated by nanovaccines. Overall, this study demonstrates a universal method to make tumor-cell-based nanovaccines for cancer immunotherapy and prevention.
Asunto(s)
InmunoterapiaRESUMEN
A critical issue in photodynamic therapy (PDT) is inadequate reactive oxygen species (ROS) generation in tumors, causing inevitable survival of tumor cells that usually results in tumor recurrence and metastasis. Existing photosensitizers frequently suffer from relatively low light-to-ROS conversion efficiency with far-red/near-infrared (NIR) light excitation due to low-lying excited states that lead to rapid non-radiative decays. Here, a neutral Ir(III) complex bearing distyryl boron dipyrromethene (BODIPY-Ir) is reported to efficiently produce both ROS and hyperthermia upon far-red light activation for potentiating in vivo tumor suppression through micellization of BODIPY-Ir to form "Micelle-Ir". BODIPY-Ir absorbs strongly at 550-750 nm with a band maximum at 685 nm, and possesses a long-lived triplet excited state with sufficient non-radiative decays. Upon micellization, BODIPY-Ir forms J-type aggregates within Micelle-Ir, which boosts both singlet oxygen generation and the photothermal effect through the high molar extinction coefficient and amplification of light-to-ROS/heat conversion, causing severe cell apoptosis. Bifunctional Micelle-Ir that accumulates in tumors completely destroys orthotopic 4T1 breast tumors via synergistic PDT/photothermal therapy (PTT) damage under light irradiation, and enables remarkable suppression of metastatic nodules in the lungs, together without significant dark cytotoxicity. The present study offers an emerging approach to develop far-red/NIR photosensitizers toward potent cancer therapy.
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Complejos de Coordinación/química , Rayos Infrarrojos , Iridio/química , Micelas , Fotoquimioterapia/métodos , Terapia Fototérmica/métodos , Animales , Compuestos de Boro/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Complejos de Coordinación/farmacología , Complejos de Coordinación/uso terapéutico , Humanos , Ratones , Neoplasias/tratamiento farmacológico , Neoplasias/terapia , Oxígeno Singlete/química , Oxígeno Singlete/metabolismoRESUMEN
Immune checkpoint blockade therapy (ICBT) targeting checkpoints, such as, cytotoxic T-lymphocyte associated protein-4 (CTLA-4), programmed death-1 (PD-1), or programmed death-ligand 1 (PD-L1), can yield durable immune response in various types of cancers and has gained constantly increasing research interests in recent years. However, the efficacy of ICBT alone is limited by low response rate and immune-related side effects. Emerging preclinical and clinical studies reveal that chemotherapy, radiotherapy, phototherapy, or other immunotherapies can reprogramm immunologically "cold" tumor microenvironment into a "hot" one, thus synergizing with ICBT. In this review, the working principle and current development of various immune checkpoint inhibitors are summarized, while the interactive mechanism and recent progress of ICBT-based synergistic therapies with other immunotherapy, chemotherapy, phototherapy, and radiotherapy in fundamental and clinical studies in the past 5 years are depicted and highlighted. Moreover, the potential issues in current studies of ICBT-based synergistic therapies and future perspectives are also discussed.
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Neoplasias , Receptor de Muerte Celular Programada 1 , Humanos , Inhibidores de Puntos de Control Inmunológico , Inmunoterapia , Neoplasias/tratamiento farmacológico , Microambiente TumoralRESUMEN
Iron oxide nanoparticles (IO NPs) have become the focus of molecular imaging probes for contrast enhanced magnetic resonance (MR) imaging due to their intrinsic magnetic and biodegradable properties, as well as long blood half-lives and low toxicity. Massive efforts have been made to explore the IO NPs as T2-weighted MR contrast agents, which have high susceptibility to induce a long-range magnetic field that interferes with diagnosis. Thus, the development of IO NPs with potent T1 relaxivity might help in providing an alternative for clinically applied gadolinium chelates. Herein, biomineralized iron oxide-polydopamine hybrid nanodots (IO/PDA-NDs) have been constructed using albumin as the nanoreactors to induce nanoprecipitation and polymerization simultaneously, facilitating T1-weighted contrast-enhancement as well as photothermal therapeutic capability. The IO nanoclusters in IO/PDA-NDs have an r1 relaxivity of 5.79 mM-1 s-1 with a relatively low r2/r1 ratio of 1.71, demonstrating the preferable iron oxide based T1 contrast agents. The high photothermal conversion coefficient and tumor targeting effect of the hybrid nanodots could result in complete tumor ablation efficacy. The biomineralization method provides a promising approach for the integration of tumor diagnosis and treatment to achieve efficient cancer theranostics.
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Antineoplásicos/farmacología , Materiales Biocompatibles/farmacología , Medios de Contraste/farmacología , Imagen por Resonancia Magnética , Nanopartículas/química , Terapia Fototérmica , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Materiales Biocompatibles/administración & dosificación , Materiales Biocompatibles/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Medios de Contraste/administración & dosificación , Medios de Contraste/química , Ensayos de Selección de Medicamentos Antitumorales , Compuestos Férricos/administración & dosificación , Compuestos Férricos/química , Compuestos Férricos/farmacología , Indoles/administración & dosificación , Indoles/química , Indoles/farmacología , Inyecciones Intravenosas , Ratones , Tamaño de la Partícula , Polímeros/administración & dosificación , Polímeros/química , Polímeros/farmacología , Propiedades de SuperficieRESUMEN
Triple-negative breast cancer (TNBC) remains with highest incidence and mortality rates among females, and a critical bottleneck lies in rationally establishing potent therapeutics against TNBC. Here, the self-assembled micellar nanoarchitecture of heavy-atom-modulated supramolecules with efficient cytoplasmic translocation and tunable photoconversion is shown, for potent suppression against primary, metastatic, and recurrent TNBC. Multi-iodinated boron dipyrromethene micelles yield tunable photoconversion into singlet oxygen and a thermal effect, together with deep penetration and subsequent cytoplasmic translocation at the tumor. Tetra-iodinated boron dipyrromethene micelles (4-IBMs) particularly show a distinctly enhanced cooperativity of antitumor efficiency through considerable expressions of apoptotic proteins, potently suppressing subcutaneous, and orthotopic TNBC models, together with reduced oxygen dependence. Furthermore, 4-IBMs yield preferable anti-metastatic and anti-recurrent efficacies through the inhibition of metastasis-relevant proteins, distinct immunogenic cell death, and re-education of M2 macrophages into tumoricidal M1 phenotype as compared to chemotherapy and surgical resection. These results offer insights into the cooperativity of supramolecular nanoarchitectures for potent phototherapy against TNBC.
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Nanomedicina/métodos , Neoplasias de la Mama Triple Negativas/patología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Femenino , Humanos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Serum protein as naturally essential biomacromolecules has recently emerged as a versatile carrier for diagnostic and therapeutic drug delivery for cancer nanomedicine with superior biocompatibility, improved pharmacokinetics and enhanced targeting capacity. A variety of serum proteins have been utilized for drug delivery, mainly including albumin, ferritin/apoferritin, transferrin, low-density lipoprotein, high-density lipoprotein and hemoglobin. As evidenced by the success of paclitaxel-bound albumin nanoparticles (AbraxaneTM), serum protein-based nanoparticles have gained attractive attentions for precise biological design and potential clinical application. In this review, we summarize the general design strategies, targeting mechanisms and recent development of serum protein-based nanoparticles in the field of cancer nanomedicine. Moreover, we also concisely specify the current challenges to be addressed for a bright future of serum protein-based nanomedicines.
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Nanopartículas , Neoplasias , Sistemas de Liberación de Medicamentos , Humanos , Nanomedicina , Neoplasias/diagnóstico , Neoplasias/tratamiento farmacológico , TransferrinaRESUMEN
Near-infrared (NIR) light-responsive nanoparticles (NPs) of organic photosensitizers (PS) hold great promise as phototherapeutic agents for precision photoinduced cancer therapy. However, highly photostable PS nanoparticles with extraordinary photoconversion capacities are urgently desired to fully realize potent phototherapy. Here, NIR nonlinear organic chromophore nanoparticles (NOC-NPs) are shown as single-component PS for dually cooperative phototherapy. Upon 785 nm irradiation, excited NOC-NPs pass through intrinsic intramolecular charge transfer (ICT) channel to generate both abundant singlet oxygen and local hyperthermia, affording synergistic photodynamic therapy (PDT) and photothermal therapy (PTT) for tumor ablation. Furthermore, NOC-NPs exhibit dramatic photostability, enhanced cellular uptake, effective cytoplasmic translocation, as well as preferable tumor accumulation, further ensuring favorable in vivo singlet oxygen generation and hyperthermia for photoinduced tumor ablation. Thus, NOC-NPs may represent novel high-performance PS for synergistic photoinduced cancer therapy, providing new insights into the development of potent PS for clinical translation.
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Hipertermia Inducida , Nanopartículas , Neoplasias , Fotoquimioterapia , Línea Celular Tumoral , Humanos , Neoplasias/terapia , FototerapiaRESUMEN
Near-infrared (NIR) light-responsive nanoparticles of organic small-molecule dyes hold great promise as phototherapeutic dyes (PDs) for clinical translation due to their intrinsic merits, including well-defined structure, high purity, and good reproducibility. However, they have been explored with limited success in the development of photostable NIR PDs with extraordinary photoconversion for highly effective phototherapy. Herein, we have described amphiphilic BODIPY dye aggregates within the polymeric micelles (Micelles) as potent bifunctional PDs for dually cooperative phototherapy under NIR irradiation. Micelles possessed an intensive NIR absorption, high photostability, and favorable non-radiative transition, thereby exhibiting both remarkable singlet oxygen generation and photothermal effect under NIR light irradiation. Besides, Micelles had preferable cellular uptake, effective cytoplasmic drug translocation as well as enhanced tumor accumulation. Owing to the combined virtues, Micelles showed clinical potential as bifunctional PDs for photo-induced cancer therapy. This work thus provides a facile strategy to exploit advanced PDs for practical phototherapeutic applications.
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Compuestos de Boro/química , Colorantes/química , Interacciones Hidrofóbicas e Hidrofílicas , Micelas , Fototerapia/métodos , Polímeros/química , Línea Celular , Humanos , Rayos Infrarrojos , Oxígeno Singlete/metabolismoRESUMEN
Drug delivery systems (DDS) are defined as methods by which drugs are delivered to desired tissues, organs, cells and subcellular organs for drug release and absorption through a variety of drug carriers. Its usual purpose to improve the pharmacological activities of therapeutic drugs and to overcome problems such as limited solubility, drug aggregation, low bioavailability, poor biodistribution, lack of selectivity, or to reduce the side effects of therapeutic drugs. During 2015-2018, significant progress in the research on drug delivery systems has been achieved along with advances in related fields, such as pharmaceutical sciences, material sciences and biomedical sciences. This review provides a concise overview of current progress in this research area through its focus on the delivery strategies, construction techniques and specific examples. It is a valuable reference for pharmaceutical scientists who want to learn more about the design of drug delivery systems.
RESUMEN
Highly efficient nanoarchitectures are of great interest for achieving precise chemotherapy with minimized adverse side effects in cancer therapy. However, a major challenge remains in exploring a rational approach to synthesize spatiotemporally selective vehicles for precise cancer chemotherapy. Here, we demonstrate a rational design of bifunctional light-activatable platinum nanocomplexes (PtNCs) that produce dually cooperative cancer therapy through spatiotemporally selective thermo-chemotherapy. The Pt4+-coordinated polycarboxylic nanogel is explored as the nanoreactor template, which is exploited to synthesize bifunctional PtNCs consisting of a zero-valent Pt0 core and a surrounding bivalent Pt2+ shell with tunable ratios through a facile and controllable reduction. Without light exposure, chemotherapeutic Pt2+ ions are tightly bound on the surface of PtNCs, efficiently reducing undesirable drug leakage and nonselective damage on normal tissues/cells. Upon light exposure, PtNCs generate much heat via photothermal conversion from the Pt0 core and simultaneously trigger a rapid release of chemotherapeutic Pt2+ ions, thereby leading to the spatiotemporally light-activatable synergistic effect of thermo-chemotherapy. Moreover, PtNCs show enhanced tumor accumulation through the heat-triggered hydrophilicity-hydrophobicity transition upon immediate light exposure after injection, dramatically facilitating in vivo tumor regression through their cooperative anticancer efficiency. This rational design of spatiotemporally activatable nanoparticles provides an insightful tool for precise cancer therapy.