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1.
Chem Commun (Camb) ; 60(71): 9550-9553, 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39150078

RESUMEN

A near-infrared light-driven Janus nanomotor is constructed by collagenase-coated gold nanorods and chitosan-functionalized mesoporous organosilica nanoparticles with Mn2+ as the bridging ion. The nanomotors with excellent motility and collagenase activity can potently penetrate into tumors to sufficiently activate innate immune responses, significantly enhancing anti-tumor immune efficacy in vivo.


Asunto(s)
Oro , Inmunoterapia , Rayos Infrarrojos , Animales , Oro/química , Ratones , Quitosano/química , Humanos , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Nanopartículas/química , Nanotubos/química , Línea Celular Tumoral , Porosidad , Manganeso/química
2.
Int J Biol Macromol ; 277(Pt 2): 134276, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39084430

RESUMEN

DNA damage-based therapy is widely used in cancer treatment, yet its therapeutic efficacy is constrained by the redox homeostasis and DNA damage repair mechanisms of tumor cells. To address these limitations and enhance the efficacy of DNA damage-based therapy, HA-CuH@MTX, a copper-histidine metal-organic complex (CuH) loaded with methotrexate (MTX) and modified with hyaluronic acid (HA), was developed to amplify the DNA damage induced. In vitro experiments demonstrated that the presence of both Cu+ and Cu2+ in HA-CuH@MTX enables two-way regulated redox dyshomeostasis (RDH), achieved through Cu+-catalyzed generation of •OH and Cu2+-mediated consumption of glutathione, thereby facilitating efficient DNA oxidative damage. In addition, DNA damage repair is synergistically inhibited by impairing nucleotide synthesis via histidine metabolism and MTX downregulation of tetrahydrofolate, a crucial raw material in nucleotide synthesis. In vivo experiments with 4T1 tumor-bearing mice demonstrate 83.6 % inhibition of tumor growth by HA-CuH@MTX. This work provides a new strategy to amplify the DNA damage caused by DNA damage-based cancer therapies, and holds great potential for improving their therapeutic efficacy.


Asunto(s)
Cobre , Daño del ADN , Metotrexato , Oxidación-Reducción , Tetrahidrofolatos , Animales , Daño del ADN/efectos de los fármacos , Metotrexato/farmacología , Oxidación-Reducción/efectos de los fármacos , Ratones , Cobre/química , Tetrahidrofolatos/metabolismo , Línea Celular Tumoral , Homeostasis/efectos de los fármacos , Histidina/química , Humanos , Ácido Hialurónico/química , Regulación hacia Abajo/efectos de los fármacos , Femenino , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Ratones Endogámicos BALB C
3.
Chem Sci ; 15(2): 765-777, 2024 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-38179519

RESUMEN

A strategy for designing cancer therapeutic nanovaccines based on immunogenic cell death (ICD)-inducing therapeutic modalities is particularly attractive for optimal therapeutic efficacy. In this work, a highly effective cancer therapeutic nanovaccine (denoted as MPL@ICC) based on immunogenic photodynamic therapy (PDT) was rationally designed and fabricated. MPL@ICC was composed of a nanovehicle of MnO2 modified with a host-guest complex using amino pillar[6]arene and lactose-pyridine, a prodrug of isoniazid (INH), and chlorine e6 (Ce6). The nanovaccine exhibited excellent biosafety, good targeting ability to hepatoma cells and enrichment at tumor sites. Most importantly, it could modulate the tumor microenvironment (TME) to facilitate the existence of Mn(iii) and Mn(iii)-mediated carbon-centered radical generation with INH released from the prodrug in situ to further strengthen ICD. This is the first report on Mn(iii)-mediated generation of carbon-centered radicals for successful anti-tumor immunotherapy using ICD, which provides a novel strategy for designing highly efficient cancer therapeutic nanovaccines.

4.
Eur Radiol ; 34(1): 579-587, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37528300

RESUMEN

OBJECTIVES: This study was aimed to quantitatively assess hyperperfusion using arterial spin labeling (ASL) to predict hemorrhagic transformation (HT) in acute ischemic stroke (AIS) patients. METHODS: This study enrolled 98 AIS patients with anterior circulation large vessel occlusion within 24 h of symptom onset. ASL was performed before mechanical endovascular therapy. On pre-treatment ASL maps, a region with relative cerebral blood flow (CBF) ≥ 1.4 was defined as an area of hyperperfusion. The maximum CBF (CBFmax) of hyperperfusion was calculated for each patient. A non-contrast CT scan was performed during the subacute phase for the evaluation of HT. Good clinical outcome was defined as a 90-day modified Rankin scale score of 0-2. RESULTS: The CBFmax of hyperperfusion (odds ratio, 1.023; 95% confidence interval [CI], 1.005-1.042; p = 0.012) was an independent risk factor for the status of HT. The CBFmax of hyperperfusion for HT showed an area under the curve of 0.735 (95% CI, 0.588-0.882) with optimal cutoff value, sensitivity, and specificity being 146.5 mL/100 g/min, 76.9%, and 69.6%, respectively. There was a statistically significant relationship between HT grades (from no HT to PH2) and CBFmax of hyperperfusion with a Spearman rank correlation of 0.446 (p = 0.001). In addition, low CBFmax of hyperperfusion were associated with good functional outcome (95% CI, 17.130-73.910; p = 0.002). CONCLUSIONS: High CBFmax of hyperperfusion was independently associated with subsequent HT and low CBFmax of hyperperfusion linked to good functional outcome. There was a positive correlation between HT grade and CBFmax. CLINICAL RELEVANCE STATEMENT: Arterial spin labeling is a noninvasive and contrast agent-independent technique, which is sensitive in detecting hyperperfusion. This study shows that the cerebral blood flow of hyperperfusion is associated with clinical prognosis, which will benefit more patients. KEY POINTS: • Quantitative assessment of hyperperfusion using pre-treatment arterial spin labeling to predict hemorrhagic transformation and prognosis in acute ischemic stroke patients. • The maximum cerebral blood flow of hyperperfusion was associated with hemorrhagic transformation and clinical prognosis and higher maximum cerebral blood flow of hyperperfusion was associated with higher grade hemorrhagic transformation. • The maximum cerebral blood flow of hyperperfusion can predict hemorrhagic transformation which enables timely intervention to prevent parenchymal hematoma.


Asunto(s)
Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular Isquémico/complicaciones , Marcadores de Spin , Arterias , Circulación Cerebrovascular/fisiología , Isquemia Encefálica/complicaciones , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/terapia
5.
Adv Sci (Weinh) ; 11(11): e2306178, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38161219

RESUMEN

Mild magnetic hyperthermia therapy (MMHT) holds great potential in treating deep-seated tumors, but its efficacy is impaired by the upregulation of heat shock proteins (HSPs) during the treatment process. Herein, Lac-FcMOF, a lactose derivative (Lac-NH2 ) modified paramagnetic metal-organic framework (FcMOF) with magnetic hyperthermia property and thermal stability, has been developed to enhance MMHT therapeutic efficacy. In vitro studies showed that Lac-FcMOF aggravates two-way regulated redox dyshomeostasis (RDH) via magnetothermal-accelerated ferricenium ions-mediated consumption of glutathione and ferrocene-catalyzed generation of ∙OH to induce oxidative damage and inhibit heat shock protein 70 (HSP70) synthesis, thus significantly enhancing the anti-cancer efficacy of MMHT. Aggravated RDH promotes glutathione peroxidase 4 inactivation and lipid peroxidation to promote ferroptosis, which further synergizes with MMHT. H22-tumor-bearing mice treated with Lac-FcMOF under alternating magnetic field (AMF) demonstrated a 90.4% inhibition of tumor growth. This work therefore provides a new strategy for the simple construction of a magnetic hyperthermia agent that enables efficient MMHT by downregulating HSPs and promoting ferroptosis through the aggravation of two-way regulated RDH.


Asunto(s)
Ferroptosis , Hipertermia Inducida , Estructuras Metalorgánicas , Neoplasias , Animales , Ratones , Proteínas de Choque Térmico , Neoplasias/terapia , Campos Magnéticos , Oxidación-Reducción
6.
Quant Imaging Med Surg ; 13(12): 8336-8349, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38106319

RESUMEN

Background: Rhabdomyolysis (RM)-induced acute kidney injury (AKI) is a common renal disease with low survival rate and inadequate prognosis. In this study, we investigate the feasibility of chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) for assessing the progression of RM-induced AKI in a mouse model. Methods: AKI was induced in C57BL/6J mice via intramuscular injection of 7.5 mL/kg glycerol (n=30). Subsequently, serum creatinine (SCr), blood urea nitrogen (BUN), and hematoxylin-eosin (HE) and Masson staining, were performed. Longitudinal CEST-MRI was conducted on days 1, 3, 7, 15, and 30 after AKI induction using a 7.0-T MRI system. CEST-MRI quantification parameters including magnetization transfer ratio (MTR), MTR asymmetric analysis (MTRasym), apparent amide proton transfer (APT*), and apparent relayed nuclear Overhauser effect (rNOE*) were used to investigate the feasibility of detecting RM-induced renal damage. Results: Significant increases of SCr and BUN demonstrated established AKI. The HE staining revealed various degrees of tubular damage, and Masson staining indicted an increase in the degree of fibrosis in the injured kidneys. Among CEST parameters, the cortical MTR presented a significant difference, and it also showed the best diagnostic performance for AKI [area under the receiver operating characteristic curve (AUC) =0.915] and moderate negative correlations with SCr and BUN. On the first day of renal damage, MTR was significantly reduced in cortex (22.7%±0.04%, P=0.013), outer stripe of outer medulla (24.7%±1.6%, P<0.001), and inner stripe of outer medulla (27.0%±1.5%, P<0.001) compared to the control group. Longitudinally, MTR increased steadily with AKI progression. Conclusions: The MTR obtained from CEST-MRI is sensitive to the pathological changes in RM-induced AKI, indicating its potential clinical utility for the assessment of kidney diseases.

7.
Mar Drugs ; 21(11)2023 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-37999417

RESUMEN

In our chemical investigation into Penicillium sp. UJNMF0740 derived from mangrove sediment, fourteen indole diterpene analogs, including four new ones, are purified by multiple chromatographic separation methods, with their structures being elucidated by the analyses of NMR, HR-ESIMS, and ECD data. The antibacterial and neuroprotective effects of these isolates were examined, and only compounds 6 and 9 exhibited weak antibacterial activity, while compounds 5, 8, and 10 showed protective effects against the injury of PC12 cells induced by 6-hydroxydopamine (6-OHDA). Additionally, compound 5 could suppress the apoptosis and production of reactive oxygen species (ROS) in 6-OHDA-stimulated PC12 cells as well as trigger the phosphorylation of PI3K and Akt. Taken together, our work enriches the structural diversity of indole diterpenes and hints that compounds of this skeleton can repress the 6-OHDA-induced apoptosis of PC12 cells via regulating the PI3K/Akt signaling pathway, which provides evidence for the future utilization of this fascinating class of molecules as potential neuroprotective agents.


Asunto(s)
Diterpenos , Fármacos Neuroprotectores , Penicillium , Ratas , Animales , Células PC12 , Proteínas Proto-Oncogénicas c-akt/metabolismo , Oxidopamina/toxicidad , Fosfatidilinositol 3-Quinasas/metabolismo , Penicillium/química , Especies Reactivas de Oxígeno/metabolismo , Apoptosis , Diterpenos/farmacología , Diterpenos/química , Indoles/farmacología , Indoles/química , Antibacterianos/farmacología , Fármacos Neuroprotectores/farmacología
8.
Carbohydr Polym ; 311: 120762, 2023 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-37028879

RESUMEN

Multidrug resistance (MDR) which is often related to the overexpression of P-glycoprotein (P-gp) in drug-resistant cancer cells has been a major problem faced by current cancer chemotherapy. Reversing P-gp-related MDR by disrupting tumor redox homeostasis that regulates the expression of P-gp is a promising strategy. In this work, a hyaluronic acid (HA) modified nanoscale cuprous metal-organic complex (HA-CuTT) was developed to reverse P-gp-related MDR via two-way regulated redox dyshomeostasis, which was achieved by both Cu+-catalyzed generation of •OH and disulfide bonds-mediated depletion of glutathione (GSH). In vitro studies reveal that the DOX-loaded complex (HA-CuTT@DOX) has excellent targeting ability to HepG2-ADR cells due to the modification of HA and effectively induces redox dyshomeostasis in HepG2-ADR cells. Moreover, HA-CuTT@DOX can cause mitochondrial damage, decrease ATP level, and downregulate the P-gp expression, thereby leading to the reversal of MDR and the increased drug accumulation in HepG2-ADR cells. Importantly, in vivo experimental results show that it can achieve effective inhibition (89.6 %) of tumor growth in nude mice bearing HepG2-ADR cells. This is the first work to reverse P-gp-related MDR via two-way regulated redox dyshomeostasis based on a HA modified nanoscale cuprous metal-organic complex, providing a new therapeutic paradigm for effective treatment of MDR-related cancer.


Asunto(s)
Doxorrubicina , Ácido Hialurónico , Humanos , Animales , Ratones , Ácido Hialurónico/farmacología , Doxorrubicina/farmacología , Ratones Desnudos , Resistencia a Antineoplásicos , Células MCF-7 , Resistencia a Múltiples Medicamentos , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Subfamilia B de Transportador de Casetes de Unión a ATP , Oxidación-Reducción
9.
Chem Commun (Camb) ; 58(90): 12584-12587, 2022 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-36285554

RESUMEN

A disulfide-induced supra-amphiphilic co-assembly strategy for hydrophobic drug co-delivery in combination therapies was proposed based on a disulfide bond containing hydrophobic pro-drug-photosensitizer (BG) and a hydrophilic/targeting dimer lactose molecule (Lac-SS-Lac). The anti-tumor efficiency was significantly enhanced by the combination therapies of epidermal growth factor receptor (EGFR) targeted therapy and phototherapy in EGFR-positive and/or galectin overexpressed tumors.


Asunto(s)
Nanopartículas , Neoplasias , Profármacos , Humanos , Profármacos/química , Fármacos Fotosensibilizantes/uso terapéutico , Disulfuros , Nanopartículas/química , Neoplasias/tratamiento farmacológico , Receptores ErbB , Línea Celular Tumoral
10.
Front Oncol ; 12: 945102, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36033435

RESUMEN

Despite improved methods of diagnosis and the development of different treatments, mortality from lung cancer remains surprisingly high. Non-small cell lung cancer (NSCLC) accounts for the large majority of lung cancer cases. Therefore, it is important to review current methods of diagnosis and treatments of NSCLC in the clinic and preclinic. In this review, we describe, as a guide for clinicians, current diagnostic methods and therapies (such as chemotherapy, chemoradiotherapy, targeted therapy, antiangiogenic therapy, immunotherapy, and combination therapy) for NSCLC.

11.
Front Pharmacol ; 13: 909526, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35860027

RESUMEN

Cancer is a disease that seriously threatens human health. Based on the improvement of traditional treatment methods and the development of new treatment modes, the pattern of cancer treatment is constantly being optimized. Nanomedicine plays an important role in these evolving tumor treatment modalities. In this article, we outline the applications of nanomedicine in three important tumor-related fields: chemotherapy, gene therapy, and immunotherapy. According to the current common problems, such as poor targeting of first-line chemotherapy drugs, easy destruction of nucleic acid drugs, and common immune-related adverse events in immunotherapy, we discuss how nanomedicine can be combined with these treatment modalities, provide typical examples, and summarize the advantages brought by the application of nanomedicine.

12.
Quant Imaging Med Surg ; 12(7): 3889-3902, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35782235

RESUMEN

Background: As an essential physiological parameter, pH plays a critical role in maintaining cellular and tissue homeostasis. The ratiometric chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) method using clinically approved iodinated agents has emerged as one of the most promising noninvasive techniques for pH assessment. Methods: In this study, we investigated the ability to use the combination of two different nonequivalent amide protons, chosen from five iodinated agents, namely iodixanol, iohexol, iobitridol, iopamidol, and iopromide, for pH measurement. The ratio of two nonequivalent amide CEST signals was calculated and compared for pH measurements in the range of 5.6 to 7.6. To quantify the CEST signals at 4.3 and 5.5 parts per million (ppm), we employed two analytic methods: magnetization transfer ratio asymmetry and Lorentzian fitting analysis. Lastly, the established protocol was used to measure the pH values in healthy rat kidneys (n=5). Results: The combination of iodixanol and iobitridol at a ratio of 1:1 was found to be suitable for pH mapping. The saturation power level (B1) was also investigated, and a low B1 of 1.5 µT was adopted for subsequent pH measurements. Improved precision and an extended pH detection range were achieved using iodixanol and iobitridol (1:1 ratio) and a single low B1 of 1.5 µT in vitro. In vivo renal pH values were measured as 7.23±0.09, 6.55±0.15, and 6.29±0.23 for the cortex, medulla, and calyx, respectively. Conclusions: These results show that the ratiometric CEST method using two iodinated agents with nonequivalent amide protons could be used for in vivo pH mapping of the kidney under a single low B1 saturation power.

13.
Front Immunol ; 13: 915047, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35784372

RESUMEN

The gut microbiota is composed of a large number of microorganisms with a complex structure. It participates in the decomposition, digestion, and absorption of nutrients; promotes the development of the immune system; inhibits the colonization of pathogens; and thus modulates human health. In particular, the relationship between gut microbiota and gastrointestinal tumor progression has attracted widespread concern. It was found that the gut microbiota can influence gastrointestinal tumor progression in independent ways. Here, we focused on the distribution of gut microbiota in gastrointestinal tumors and further elaborated on the impact of gut microbiota metabolites, especially short-chain fatty acids, on colorectal cancer progression. Additionally, the effects of gut microbiota on gastrointestinal tumor therapy are outlined. Finally, we put forward the possible problems in gut microbiota and the gastrointestinal oncology field and the efforts we need to make.


Asunto(s)
Microbioma Gastrointestinal , Neoplasias Gastrointestinales , Ácidos Grasos Volátiles , Humanos
14.
ACS Appl Mater Interfaces ; 14(18): 20749-20761, 2022 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-35481368

RESUMEN

The development of robust phototherapeutic strategies for eradicating tumors remains a significant challenge in the transfer of cancer phototherapy to clinical practice. Here, a phototherapeutic nanococktail atovaquone/17-dimethylaminoethylamino-17-demethoxygeldanamycin/glyco-BODIPY (ADB) was developed to enhance photodynamic therapy (PDT) and photothermal therapy (PTT) via alleviation of hypoxia and thermal resistance that was constructed using supramolecular self-assembly of glyco-BODIPY (BODIPY-SS-LAC, BSL-1), hypoxia reliever atovaquone (ATO), and heat shock protein inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG). Benefiting from a glyco-targeting and glutathione (GSH) responsive units BSL-1, ADB can be rapidly taken up by hepatoma cells, furthermore the loaded ATO and 17-DMAG can be released in original form into the cytoplasm. Using in vitro and in vivo results, it was confirmed that ADB enhanced the synergetic PDT and PTT upon irradiation using 685 nm near-infrared light (NIR) under a hypoxic tumor microenvironment where ATO can reduce O2 consumption and 17-DMAG can down-regulate HSP90. Moreover, ADB exhibited good biosafety, and tumor eradication in vivo. Hence, this as-developed phototherapeutic nanococktail overcomes the substantial obstacles encountered by phototherapy in tumor treatment and offers a promising approach for the eradication of tumors.


Asunto(s)
Nanopartículas , Fotoquimioterapia , Atovacuona , Línea Celular Tumoral , Humanos , Hipoxia/tratamiento farmacológico , Nanopartículas/uso terapéutico , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Fototerapia
15.
Chem Commun (Camb) ; 58(24): 3945-3948, 2022 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-35244637

RESUMEN

A GLUTs/GSH cascade targeting-responsive bioprobe, GluCC, was rationally designed and synthesized for the first time via the coordination of copper ions with a glucose-modified coumarin derivative ligand (GluC). GluCC can specifically detect circulating tumor cells (CTCs) in lung metastatic mice models by targeting the Warburg effect and responding to overexpressed glutathione in the tumor microenvironment. This bioprobe with a simple detection procedure has significant advantages for CTC detection.


Asunto(s)
Técnicas Biosensibles , Células Neoplásicas Circulantes , Animales , Biomarcadores de Tumor , Glutatión , Ratones , Células Neoplásicas Circulantes/patología , Microambiente Tumoral
16.
Huan Jing Ke Xue ; 43(2): 1059-1068, 2022 Feb 08.
Artículo en Chino | MEDLINE | ID: mdl-35075880

RESUMEN

Soil enzyme activity is an important index to characterize the nutrient requirements and nutrient limitations of soil microorganisms. In this study, Pinus massoniana plantations of different stand ages (9, 17, 26, 34, and 43 a) in mid-subtropical China were taken as the research object; the activities of ß-glucosidase (BG), N-acetyl-ß-glucosaminidase (NAG), leucine amino-peptidase (LAP), acid phosphatase (AP), polyphenol oxidase (POX), and peroxidase (POD) were determined; and soil enzyme stoichiometric ratios were also calculated to investigate the soil microbial nutrient limitations of P. massoniana plantation development. The results showed that the activities of BG, NAG, AP, POX, and POD were enhanced with the increase in stand age, and the activity of LAP was the lowest at 17 a, which showed a significant difference and fluctuated among the neighboring stand ages. The soil enzyme C:N:P stoichiometric ratio was 1:1:0.56, which deviated from the global ecosystem enzyme C:N:P stoichiometric ratio (1:1:1). The enzyme C:N increased, whereas the enzyme N:P decreased, with increasing stand age, and both ratios tended to be stable after 17 a. There was no significant difference in enzyme N:P among different stand ages. The vector length of enzyme stoichiometry was not significantly different among the five stand ages. The vector angles increased with the increase in stand ages and tended to be stable after 17 a of stand age, but the angles were less than 45°. Redundancy analysis (RDA) revealed that soil carbon quality index and pH were the main factors influencing soil enzyme activity and the associated stoichiometric ratio. Our findings indicated that P. massoniana plantation soil microorganisms at different growth stages were all subjected to N limitation, and the N limitation was alleviated with the increase in stand age; however, the P requirement was gradually enhanced. Therefore, the management of P. massoniana plantations should take care to increase nitrogen fertilizer at the early growth stage of P. massoniana, and more phosphorus fertilizers need to be applied with nitrogen at the late growth stage in order to maintain the productivity and sustainable development of P. massoniana plantations.


Asunto(s)
Pinus , Suelo , Carbono/análisis , China , Ecosistema , Nitrógeno/análisis , Fósforo/análisis , Microbiología del Suelo
17.
Chem Commun (Camb) ; 56(73): 10642-10645, 2020 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-32766652

RESUMEN

Supramolecular glyco-nanovesicles (SeSe-(P5)2⊃Man-NH3+) based on the host-guest complex of a diselenium-bridged pillar[5]arene dimer and a mannose derivative have been successfully developed for the first time, which possessed tumor microenvironment-responsiveness and specific targetability due to their diselenium bonds and mannose units, respectively.


Asunto(s)
Calixarenos/química , Portadores de Fármacos/química , Manósidos/química , Nanoestructuras/química , Compuestos de Organoselenio/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Doxorrubicina/farmacología , Liberación de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Células HEK293 , Humanos , Microambiente Tumoral/fisiología
18.
Artículo en Inglés | MEDLINE | ID: mdl-32695767

RESUMEN

Numerous tissue-engineered constructs have been investigated as bone scaffolds in regenerative medicine. However, it remains challenging to non-invasively monitor the biodegradation and remodeling of bone grafts after implantation. Herein, silk fibroin/hydroxyapatite scaffolds incorporated with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles were successfully synthesized, characterized, and implanted subcutaneously into the back of nude mice. The USPIO labeled scaffolds showed good three-dimensional porous structures and mechanical property, thermal stability for bone repair. After loaded with bone marrow-derived mesenchymal stem cells (BMSCs), the multifunctional scaffolds promoted cell adhesion and growth, and facilitated osteogenesis by showing increased levels of alkaline phosphatase activity and up-regulation of osteoblastic genes. Furthermore, in vivo quantitative magnetic resonance imaging (MRI) results provided valuable information on scaffolds degradation and bone formation simultaneously, which was further confirmed by computed tomography and histological examination. These findings demonstrated that the incorporation of USPIO into BMSCs-loaded multifunctional scaffold system could be feasible to noninvasively monitor bone regeneration by quantitative MRI. This tissue engineering strategy provides a promising tool for translational application of bone defect repair in clinical scenarios.

19.
Quant Imaging Med Surg ; 9(9): 1579-1591, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31667143

RESUMEN

BACKGROUND: To develop liposomes loaded with iodinated agents as nanosized CT/MRI bimodal contrast agents for monitoring liposome-mediated drug delivery. METHODS: Rhodamine-labeled iodixanol (VisipaqueTM)-loaded liposomes (IX-lipo) were prepared and tested for their properties as a diamagnetic CEST contrast agent in vitro. Mice bearing subcutaneous CT26 colon tumors were injected i.v. with 1 g/kg (535 mg iodine/kg) IX-lipo, and in vivo CT and CEST MR images were acquired on day 3. CT and CEST MR images were also acquired for tumor-bearing mice co-injected with IX-lipo and tumor necrosis factor (TNF-α). RESULTS: In addition to CT contrast, IX-lipo exhibited a strong CEST contrast similar to its non-liposomal form, with a detectability of ~2 nM per liposome. Both CT imaging and CEST MRI showed that i.v. injection of IX-lipo resulted in a rim enhancement of CT26 tumors with a heterogeneous central distribution. In contrast, co-injection of TNF-α caused a significantly augmented CT/MRI contrast in the tumor center. The intratumoral biodistribution of IX-lipo correlated well to the rhodamine patterns observed with fluorescence microscopy. CONCLUSIONS: We have developed a CT/MRI bimodal imaging approach for monitoring the delivery and biodistribution of liposomes by loading them with the clinically approved X-ray/CT contrast agent iodixanol. Our approach may be easily adapted for other-FDA approved iodinated agents and thus has great translational potential.

20.
Acta Biomater ; 74: 334-343, 2018 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-29753138

RESUMEN

Ternary copper-based chalcogenide nanomaterials have become rather attractive due to the near-infrared (NIR) response in cancer theranostic fields. However, it is still challenging to further improve the theranostic efficiency of these nanomaterials. Herein, Cu-Sb-S nanoparticles (NPs) around 24 nm are synthesized facilely and functionalized with poly(vinylpyrrolidone) (PVP). Under the NIR irradiation, the resultant PVP-Cu-Sb-S NPs exhibit a relatively high photothermal conversion efficiency of 53.16% and a simultaneous reactive oxygen species (ROS) generation effect. Due to these outstanding photothermal/photodynamic effects, excellent tumor ablation results can be achieved by the combination of PVP-Cu-Sb-S NPs and 808 nm NIR laser treatments without obvious side effect. In addition, they show remarkable contrast enhancement according to in vitro and in vivo photoacoustic (PA) imaging. These PVP-Cu-Sb-S NPs could be served as a multifunctional nanotheranostic agent for PA imaging, photothermal/photodynamic cancer therapy. STATEMENT OF SIGNIFICANCE: Highly theranostic efficiency ternary copper-based chalcogenide nanomaterials has not been fully developed yet. Herein we report the PVP-Cu-Sb-S nanoparticles (NPs) with relatively high photothermal efficiency, simultaneous reactive oxygen species generation effect and photoacoustic imaging capability. The photothermal conversion efficiency of PVP-Cu-Sb-S NPs is higher than most of copper-based chalcogenide nanomaterials reported before. These findings provide a new kind of ternary copper-based chalcogenide with an enhanced theranostic effect, which could be served as a promising multifunctional nanotheranostic agent in the field of biomedical application.


Asunto(s)
Hipertermia Inducida/métodos , Rayos Infrarrojos , Neoplasias Experimentales , Técnicas Fotoacústicas/métodos , Fotoquimioterapia/métodos , Animales , Antimonio/química , Antimonio/farmacología , Cobre/química , Cobre/farmacología , Femenino , Células HeLa , Humanos , Ratones , Ratones Endogámicos BALB C , Nanopartículas/química , Nanopartículas/uso terapéutico , Neoplasias Experimentales/diagnóstico por imagen , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/patología , Neoplasias Experimentales/terapia , Povidona/química , Povidona/farmacología , Sulfuros/química , Sulfuros/farmacología , Nanomedicina Teranóstica/métodos
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