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1.
Semin Cancer Biol ; 89: 61-75, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36682438

RESUMO

Over the last decade, the nanomedicine has experienced unprecedented development in diagnosis and management of diseases. A number of nanomedicines have been approved in clinical use, which has demonstrated the potential value of clinical transition of nanotechnology-modified medicines from bench to bedside. The application of artificial intelligence (AI) in development of nanotechnology-based products could transform the healthcare sector by realizing acquisition and analysis of large datasets, and tailoring precision nanomedicines for cancer management. AI-enabled nanotechnology could improve the accuracy of molecular profiling and early diagnosis of patients, and optimize the design pipeline of nanomedicines by tuning the properties of nanomedicines, achieving effective drug synergy, and decreasing the nanotoxicity, thereby, enhancing the targetability, personalized dosing and treatment potency of nanomedicines. Herein, the advances in AI-enabled nanomedicines in cancer management are elaborated and their application in diagnosis, monitoring and therapy as well in precision medicine development is discussed.


Assuntos
Nanomedicina , Neoplasias , Humanos , Inteligência Artificial , Nanotecnologia , Sistemas de Liberação de Medicamentos , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico
2.
Anal Chem ; 96(6): 2550-2558, 2024 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-38314707

RESUMO

Cancer-related extracellular vesicles (EVs) are considered important biomarkers for cancer diagnosis because they can convey a large amount of information about tumor cells. In order to detect cancer-related EVs efficiently, an electrochemiluminescence (ECL) sensor for the specific identification and highly sensitive detection of EVs in the plasma of cancer patients was constructed based on dual recognitions by glycosyl-imprinted polymer (GIP) and aptamer. The characteristic glycosyl Neu5Ac-α-(2,6)-Gal-ß-(1-4)-GlcNAc trisaccharide on the surface of EVs was used as a template molecule and 3-aminophenylboronic acid as a functional monomer to form a glycosyl-imprinted polymer by electropolymerization. After glycosyl elution, the imprinted film specifically recognized and adsorbed the EVs in the sample, and then the CD63 aptamer-bipyridine ruthenium (Aptamer-Ru(bpy)) was added to combine with the CD63 glycoprotein on the extracellular vesicle's surface, thus providing secondary recognition of the EVs. Finally, the EVs were quantitatively detected according to the ECL signal produced by the labeled bipyridine ruthenium. When more EVs were captured by the imprinted film, more probes were obtained after incubation, and the ECL signal was stronger. Under the optimized conditions, the ECL signal showed a good linear relationship with the concentration of EVs in the range of 9.5 × 102 to 9.5 × 107 particles/mL, and the limit of detection was 641 particles/mL. The GIP sensor can discriminate between the EV contents of cancer patients and healthy controls with high accuracy. Because of its affordability, high sensitivity, and ease of use, it is anticipated to be employed for cancer early detection and diagnosis.


Assuntos
Técnicas Biossensoriais , Vesículas Extracelulares , Neoplasias , Rutênio , Humanos , Medições Luminescentes , Oligonucleotídeos , Polímeros , Técnicas Eletroquímicas , Neoplasias/diagnóstico
3.
Small ; : e2401397, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898735

RESUMO

Pyroptosis, an inflammatory cell death, plays a pivotal role in activating inflammatory response, reversing immunosuppression and enhancing anti-tumor immunity. However, challenges remain regarding how to induce pyroptosis efficiently and precisely in tumor cells to amplify anti-tumor immunotherapy. Herein, a pH-responsive polydopamine (PDA) nanocluster, perfluorocarbon (PFC)@octo-arginine (R8)-1-Hexadecylamine (He)-porphyrin (Por)@PDA-gambogic acid (GA)-cRGD (R-P@PDA-GC), is rationally design to augment phototherapy-induced pyroptosis and boost anti-tumor immunity through a two-input programmed cascade therapy. Briefly, oxygen doner PFC is encapsulated within R8 linked photosensitizer Por and He micelles as the core, followed by incorporation of GA and cRGD peptides modified PDA shell, yielding the ultimate R-P@PDA-GC nanoplatforms (NPs). The pH-responsive NPs effectively alleviate hypoxia by delivering oxygen via PFC and mitigate heat resistance in tumor cells through GA. Upon two-input programmed irradiation, R-P@PDA-GC NPs significantly enhance reactive oxygen species production within tumor cells, triggering pyroptosis via the Caspase-1/GSDMD pathway and releasing numerous inflammatory factors into the TME. This leads to the maturation of dendritic cells, robust infiltration of cytotoxic CD8+ T and NK cells, and diminution of immune suppressor Treg cells, thereby amplifying anti-tumor immunity.

4.
J Nanobiotechnology ; 22(1): 180, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622591

RESUMO

To address the limitations of traditional photothermal therapy (PTT)/ photodynamic therapy (PDT) and real-time cancer metastasis detection, a pH-responsive nanoplatform (NP) with dual-modality imaging capability was rationally designed. Herein, 1 H,1 H-undecafluorohexylamine (PFC), served as both an oxygen carrier and a 19F magnetic resonance imaging (MRI) probe, and photosensitizer indocyanine green (ICG) were grafted onto the pH-responsive peptide hexahistidine (H6) to form H6-PFC-ICG (HPI). Subsequently, the heat shock protein 90 inhibitor, gambogic acid (GA), was incorporated into hyaluronic acid (HA) modified HPI (HHPI), yielding the ultimate HHPI@GA NPs. Upon self-assembly, HHPI@GA NPs passively accumulated in tumor tissues, facilitating oxygen release and HA-mediated cell uptake. Once phagocytosed by lysosomes, protonation of H6 was triggered due to the low pH, resulting in the release of GA. With near-infrared laser irradiation, GA-mediated decreased HSP90 expression and PFC-mediated increased ROS generation amplified the PTT/PDT effect of HHPI@GA, leading to excellent in vitro and in vivo anticancer efficacies. Additionally, the fluorescence and 19F MRI dual-imaging capabilities of HHPI@GA NPs enabled effective real-time primary cancer and lung metastasis monitoring. This work offers a novel approach for enhanced cancer phototherapy, as well as precise cancer diagnosis.


Assuntos
Neoplasias Pulmonares , Nanopartículas , Fotoquimioterapia , Humanos , Fototerapia/métodos , Verde de Indocianina , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/terapia , Oxigênio , Concentração de Íons de Hidrogênio , Linhagem Celular Tumoral
5.
J Nanobiotechnology ; 22(1): 106, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38468300

RESUMO

Understanding the intricate nanoscale architecture of neuronal myelin during central nervous system development is of utmost importance. However, current visualization methods heavily rely on electron microscopy or indirect fluorescent method, lacking direct and real-time imaging capabilities. Here, we introduce a breakthrough near-infrared emissive curcumin-BODIPY derivative (MyL-1) that enables direct visualization of myelin structure in brain tissues. The remarkable compatibility of MyL-1 with stimulated emission depletion nanoscopy allows for unprecedented super-resolution imaging of myelin ultrastructure. Through this innovative approach, we comprehensively characterize the nanoscale myelinogenesis in three dimensions over the course of brain development, spanning from infancy to adulthood in mouse models. Moreover, we investigate the correlation between myelin substances and Myelin Basic Protein (MBP), shedding light on the essential role of MBP in facilitating myelinogenesis during vertebral development. This novel material, MyL-1, opens up new avenues for studying and understanding the intricate process of myelinogenesis in a direct and non-invasive manner, paving the way for further advancements in the field of nanoscale neuroimaging.


Assuntos
Compostos de Boro , Curcumina , Animais , Camundongos , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Neurônios , Microscopia Eletrônica
6.
Chem Soc Rev ; 52(1): 47-96, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36427082

RESUMO

Cancer radio-immunotherapy, integrating external/internal radiation therapy with immuno-oncology treatments, emerges in the current management of cancer. A growing number of pre-clinical studies and clinical trials have recently validated the synergistic antitumor effect of radio-immunotherapy, far beyond the "abscopal effect", but it suffers from a low response rate and toxicity issues. To this end, nanomedicines with an optimized design have been introduced to improve cancer radio-immunotherapy. Specifically, these nanomedicines are elegantly prepared by incorporating tumor antigens, immuno- or radio-regulators, or biomarker-specific imaging agents into the corresponding optimized nanoformulations. Moreover, they contribute to inducing various biological effects, such as generating in situ vaccination, promoting immunogenic cell death, overcoming radiation resistance, reversing immunosuppression, as well as pre-stratifying patients and assessing therapeutic response or therapy-induced toxicity. Overall, this review aims to provide a comprehensive landscape of nanomedicine-assisted radio-immunotherapy. The underlying working principles and the corresponding design strategies for these nanomedicines are elaborated by following the concept of "from bench to clinic". Their state-of-the-art applications, concerns over their clinical translation, along with perspectives are covered.


Assuntos
Nanomedicina , Neoplasias , Humanos , Nanomedicina/métodos , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Imunoterapia/métodos , Antígenos de Neoplasias
7.
J Environ Manage ; 351: 119757, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38100863

RESUMO

Spatial conflicts of land use (SCLU) arise during land-use change, which causes an imbalance of land-use spatial patterns and negatively affects society, the economy, and ecology. Previous research has focused on identifying and measuring SCLU, with less attention on the negative effects. The incorporation of risk assessment methods to evaluate potential conflict risks has been limited. The current study presents methods for measuring SCLU and assessing potential conflict risks from the ecological environment perspective. The spatial comprehensive conflicts index and potential conflict risk index were used to identify and measure the SCLU and to assess and warn against potential conflict risks, respectively, based on a case study in the Ili River Valley in China. The impacts of terrain restriction and land-use change on the SCLU were explored. Results indicate that (1) the SCLU area in the Ili River Valley decreased by 2,608 km2 from 2010 to 2020, compared to the previous decade, the degree of conflict weakened, and the main body of the SCLU gradually shifted northwest. (2) The potential risk areas cover 20,268 km2 in 2020-2030 and are mainly distributed in the "Khorgas City-Huocheng County-Yining City-Yining County" group of towns, as well as along the Ili-Kunes rivers and in the ecological protection zone in the south of the Ili River Valley, which shows the clustering along the city and distribution along the river in the spatial pattern. (3) Topography had a significant impact on the SCLU, and the main types of land-use change in the severe-conflict zone were the reduction of grassland and the expansion of arable and built-up land. For future conflict mitigation in the Ili River Valley, cautioning against urban sprawl and safeguarding land ecological security is critical. This study systematically investigates and analyzes SCLU across three dimensions: theory, methodology, and application to produce a theoretical and practical framework to identify SCLU and assess potential conflict risks.


Assuntos
Conservação dos Recursos Naturais , Rios , Cidades , China , Medição de Risco , Ecossistema
8.
J Environ Manage ; 363: 121411, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38861887

RESUMO

Rural areas are the main source of ecosystem services in arid and semi-arid areas, and ecosystem services are the background conditions for rural revitalization. In this study, the spatial pattern of key ecosystem services in the countryside was assessed, and the trade-offs and synergistic relationships among ecosystem services were investigated, using the Tacheng-Emin Basin in China as the study area. Finally, the types of ecological function zoning and development strategies for the countryside are proposed. The results showed that: (1) the area of ecological land was large, and the average land use intensity was 2.48, which belonged to the medium intensity. (2) The mean values of the six ecosystem services are all in the middle and lower classes, and the spatial distribution of the five ecosystem services is similar, except for food production. (3) Except for grain production, the other five ecosystem services showed positive feedback to elevation. The other five ecosystem services are synergistic, and there are trade-offs between grain production and other ecosystem services. In the nonlinear interaction mechanism of ecosystem services, the fluctuation constraint occupies the largest proportion. (4) At smaller spatial scales, there are more types of ecosystem service clusters. Combining the results of the study, the villages in the study area can be categorized into five types. This study formulates five priority levels of rural ecological revitalization and proposes different development recommendations for the sustainable development of each type of village. This study is helpful for the fine management of land resources and the revitalization of rural ecology and provides a reference for the sustainable development of ecosystem services in arid and semi-arid areas.


Assuntos
Conservação dos Recursos Naturais , Ecossistema , China , Ecologia
9.
Small ; 19(24): e2207898, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36932938

RESUMO

Chemotherapeutics can induce immunogenic cell death (ICD) by triggering autophagy and mediate antitumor immunotherapy. However, using chemotherapeutics alone can only cause mild cell-protective autophagy and be incapable of inducing sufficient ICD efficacy. The participation of autophagy inducer is competent to enhance autophagy, so the level of ICD is promoted and the effect of antitumor immunotherapy is highly increased. Herein, tailor-made autophagy cascade amplification polymeric nanoparticles STF@AHPPE are constructed to enhance tumor immunotherapy. Arginine (Arg), polyethyleneglycol-polycaprolactone, and epirubicin (EPI) are grafted onto hyaluronic acid (HA) via disulfide bond to form the AHPPE nanoparticles and autophagy inducer STF-62247 (STF) is loaded. When STF@AHPPE nanoparticles target to tumor tissues and efficiently enter into tumor cells with the help of HA and Arg, the high glutathione concentration leads to the cleavage of disulfide bond and the release of EPI and STF. Finally, STF@AHPPE induces violent cytotoxic autophagy and strong ICD efficacy. As compared to AHPPE nanoparticles, STF@AHPPE nanoparticles kill the most tumor cells and show the more obvious ICD efficacy and immune activation ability. This work provides a novel strategy for combining tumor chemo-immunotherapy with autophagy induction.


Assuntos
Antineoplásicos , Nanopartículas , Neoplasias , Humanos , Antineoplásicos/farmacologia , Autofagia , Imunoterapia , Dissulfetos/farmacologia , Linhagem Celular Tumoral , Microambiente Tumoral
10.
Metab Eng ; 77: 64-75, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36948242

RESUMO

Butyl butyrate has broad applications in foods, cosmetics, solvents, and biofuels. Microbial synthesis of bio-based butyl butyrate has been regarded as a promising approach recently. Herein, we engineered Clostridium tyrobutyricum ATCC 25755 to achieve de novo biosynthesis of butyl butyrate from fermentable sugars. Through introducing the butanol synthetic pathway (enzyme AdhE2), screening alcohol acyltransferases (AATs), adjusting transcription of VAAT and adhE2 (i.e., optimizing promoter), and efficient supplying butyryl-CoA, an excellent engineered strain, named MUV3, was obtained with ability to produce 4.58 g/L butyl butyrate at 25 °C with glucose in serum bottles. More NADH is needed for butyl butyrate synthesis, thus mannitol (the more reduced substrate) was employed to produce butyl butyrate. Ultimately, 62.59 g/L butyl butyrate with a selectivity of 95.97%, and a yield of 0.21 mol/mol was obtained under mannitol with fed-batch fermentation in a 5 L bioreactor, which is the highest butyl butyrate titer reported so far. Altogether, this study presents an anaerobic fermentative platform for de novo biosynthesis of butyl butyrate in one step, which lays the foundation for butyl butyrate biosynthesis from renewable biomass feedstocks.


Assuntos
Clostridium tyrobutyricum , Clostridium tyrobutyricum/genética , Clostridium tyrobutyricum/metabolismo , Butiratos/metabolismo , 1-Butanol/metabolismo , Fermentação , Manitol/metabolismo
11.
Psychol Med ; : 1-12, 2023 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-36748350

RESUMO

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a clinically heterogeneous neurodevelopmental disorder defined by characteristic behavioral and cognitive features. Abnormal brain dynamic functional connectivity (dFC) has been associated with the disorder. The full spectrum of ADHD-related variation of brain dynamics and its association with behavioral and cognitive features remain to be established. METHODS: We sought to identify patterns of brain dynamics linked to specific behavioral and cognitive dimensions using sparse canonical correlation analysis across a cohort of children with and without ADHD (122 children in total, 63 with ADHD). Then, using mediation analysis, we tested the hypothesis that cognitive deficits mediate the relationship between brain dynamics and ADHD-associated behaviors. RESULTS: We identified four distinct patterns of dFC, each corresponding to a specific dimension of behavioral or cognitive function (r = 0.811-0.879). Specifically, the inattention/hyperactivity dimension was positively associated with dFC within the default mode network (DMN) and negatively associated with dFC between DMN and the sensorimotor network (SMN); the somatization dimension was positively associated with dFC within DMN and SMN; the inhibition and flexibility dimension and fluency and memory dimensions were both positively associated with dFC within DMN and between DMN and SMN, and negatively associated with dFC between DMN and the fronto-parietal network. Furthermore, we observed that cognitive functions of inhibition and flexibility mediated the relationship between brain dynamics and behavioral manifestations of inattention and hyperactivity. CONCLUSIONS: These findings document the importance of distinct patterns of dynamic functional brain activity for different cardinal behavioral and cognitive features related to ADHD.

12.
Neurochem Res ; 48(2): 458-470, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36322370

RESUMO

BACKGROUND: Subarachnoid hemorrhage (SAH) is a cerebral hemorrhagic disease with a high disability and fatality rate. Cell pyroptosis is involved in the brain injury following SAH. Here, we explored the effect of HDAC inhibitor SAHA against cell pyroptosis after SAH. METHODS: The rat SAH model was established by endovascular perforation and the rat microglia were treated with 25 µm oxyhemoglobin (OxyHb) for 24 h to mimic SAH model in vitro. Neurological score and brain edema were assessed in rat SAH model. TUNEL staining detected apoptosis. qRT-PCR and western blotting were employed to detect expression levels of miR-340, NEK7 and inflammatory cytokines. ELISA assay determined the secretion of IL-1ß and IL-18 in rat serum and cell supernatant. A lactate dehydrogenase (LDH) kit measured the LDH activity in rat primary microglia. Microglia pyroptosis was detected by flow cytometry. RIP and dual luciferase reporter assays confirmed the binding relationship between miR-340 and NEK7. RESULTS: SAHA alleviated neurological dysfunction, inflammatory injury and microglia pyroptosis in SAH rats. SAHA suppressed LDH release, inflammatory factor expression and pyroptosis in microglia treated with OxyHb. Meanwhile, SAHA increased miR-340 expression and inhibited NEK7 level in vivo and in vitro SAH models. Further, miR-340 directly targeted NEK7 to inhibit the NLRP3 signaling pathway. Knockdown of miR-340 or overexpression of NEK7 reversed the suppressive effects of SAHA on microglia inflammation and pyroptosis. Additionally, knockdown of NEK7 impaired microglia inflammation and pyroptosis induced by miR-340 inhibitor. CONCLUSION: HDAC inhibitor SAHA ameliorates microglia pyroptosis in SAH through triggering miR-340 expression to suppress NEK7 signaling. This novel mechanism provides promise for SAHA in SAH treatment.


Assuntos
MicroRNAs , Hemorragia Subaracnóidea , Ratos , Animais , Hemorragia Subaracnóidea/tratamento farmacológico , Hemorragia Subaracnóidea/metabolismo , Piroptose , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Transdução de Sinais , Inflamação/metabolismo , MicroRNAs/metabolismo
13.
Mol Pharm ; 20(2): 829-852, 2023 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-36588471

RESUMO

Epidermal growth factor receptor (EGFR) plays a key role in signal transduction pathways associated with cell proliferation, growth, and survival. Its overexpression and aberrant activation in malignancy correlate with poor prognosis and short survival. Targeting inhibition of EGFR by small-molecular tyrosine kinase inhibitors (TKIs) is emerging as an important treatment model besides of chemotherapy, greatly reshaping the landscape of cancer therapy. However, they are still challenged by the off-targeted toxicity, relatively limited cancer types, and drug resistance after long-term therapy. In this review, we summarize the recent progress of oral, pulmonary, and injectable drug delivery systems for enhanced and targeting TKI delivery to tumors and reduced side effects. Importantly, EGFR-TKI-based combination therapies not only greatly broaden the applicable cancer types of EGFR-TKI but also significantly improve the anticancer effect. The mechanisms of TKI resistance are summarized, and current strategies to overcome TKI resistance as well as the application of TKI in reversing chemotherapy resistance are discussed. Finally, we provide a perspective on the future research of EGFR-TKI-based cancer therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB , Mutação
14.
Sensors (Basel) ; 23(18)2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37765920

RESUMO

Bridge inspection and monitoring are usually used to evaluate the status and integrity of bridge structures to ensure their safety and reliability. Computer vision (CV)-based methods have the advantages of being low cost, simple to operate, remote, and non-contact, and have been widely used in bridge inspection and monitoring in recent years. Therefore, this paper reviews three significant aspects of CV-based methods, including surface defect detection, vibration measurement, and vehicle parameter identification. Firstly, the general procedure for CV-based surface defect detection is introduced, and its application for the detection of cracks, concrete spalling, steel corrosion, and multi-defects is reviewed, followed by the robot platforms for surface defect detection. Secondly, the basic principle of CV-based vibration measurement is introduced, followed by the application of displacement measurement, modal identification, and damage identification. Finally, the CV-based vehicle parameter identification methods are introduced and their application for the identification of temporal and spatial parameters, weight parameters, and multi-parameters are summarized. This comprehensive literature review aims to provide guidance for selecting appropriate CV-based methods for bridge inspection and monitoring.

15.
J Am Chem Soc ; 144(3): 1455-1463, 2022 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-35029384

RESUMO

Self-inhibition has been observed widely in hierarchical biochemical processes but has yet to be demonstrated in pure molecular physical rather than chemical or biological processes. Herein, we report an unprecedented example of self-inhibition during the supramolecular chirality induction, memory, erasure, and inversion processes of pillar[5]arene (P[5]) derivatives. The addition of chiral alanine ethyl ester to bulky substituent-modified P[5]s led to time-dependent chirality induction due to the shift in the equilibrium of the SP and RP conformers P[5]. Intriguingly, more chiral inducers led to more intensive final chiroptical properties but lower chiral induction rates. Thus, the chiral inducer plays the role of both activator and inhibitor. Such self-inhibition essentially arises from kinetics manipulation of three tandem equilibria. Moreover, the chiroptical properties could be memorized by replacing the chiral inducer with an achiral competitive binder, and the chiroptical signal could be erased and reversed by an antipodal chiral inducer, which also showed the self-inhibition property.

16.
Biomacromolecules ; 23(12): 5202-5212, 2022 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-36287618

RESUMO

Poor antitumor drug penetration into tumor tissues is a global challenge in clinical cancer treatment. Here, we reported a smart multistage "Trojan Horse"-inspired bovine serum albumin (BSA)-coated liposome (HBM), including the mimics of capsid and secondary BSA-coated polymeric nanoparticles (NPs) for enhancing tumor penetration and antitumor efficacy. These drug-loaded polymeric NPs possess a capsid-like component, a well-distributed nanostructure (size: 190.1 ± 4.98 nm, PDI: 0.259), and an excellent drug loading content (15.85 ± 1.36%). Meaningfully, after the smart multistage BSA-coated liposome targeted the tumor tissue, the mimics of capsid were "taken off" under the condition of tumor-specific enzymes, releasing "Heart" BSA-modified secondary NPs to increase the ability to penetrate tumor cells for enhancing antitumor efficacy. As expected, the HBM efficiently achieves high drug penetration into PAN02 tumor cells. Moreover, compared to free DOX and HM (HBM without BSA) NPs, DOX/HBM NPs exhibited the strongest tumor penetration and the highest cytotoxicity against PAN02 tumor cells both in vitro (IC50 = 0.141 µg/mL) and in vivo. This smart multistage "Trojan Horse"-inspired BSA-coated liposome should provide a new hathpace for further development of polymeric NPs in clinical treatment.


Assuntos
Nanopartículas , Neoplasias , Humanos , Soroalbumina Bovina , Lipossomos/uso terapêutico , Portadores de Fármacos/uso terapêutico , Neoplasias/tratamento farmacológico , Linhagem Celular Tumoral
17.
Bioorg Med Chem Lett ; 75: 128952, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36031018

RESUMO

Prostate cancer (PCa) is the most frequently diagnosed male malignant tumor and remains the second leading cause of male cancer mortality in western countries. The development of novel antiandrogens to circumvent the drug resistance in anti-PCa treatment is highly demanded. Herein, we identified that gossypol (GOS) specificly inhibited the AR signaling. Further optimization of GOS derivatives led to the discovery of compound XY-32. XY-32 efficiently inhibits AR signaling with the IC50 of 1.23 µM. XY-32 downregulates both the full-length AR and the AR variable splice AR-V7 via suppressing the mRNA expression. It inhibits the proliferation of CRPC cells such as the LNCaP cells, the PC-3 cells, and enzalutamide resistance 22Rv1 cells. The work demonstrates the GOS derivatives represent a novel series of anti-androgen to conquer the acquired AR mutations or AR splice variants induced drug resistance of mCRPC.


Assuntos
Gossipol , Neoplasias de Próstata Resistentes à Castração , Antagonistas de Androgênios/farmacologia , Antagonistas de Receptores de Andrógenos/farmacologia , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Gossipol/farmacologia , Humanos , Masculino , Nitrilas , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias de Próstata Resistentes à Castração/patologia , RNA Mensageiro , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo
18.
Nanotechnology ; 33(34)2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35550566

RESUMO

Fe-based metal-organic frameworks (MOFs) are promising drug delivery materials due to their large surface area, high stability, and biocompatibility. However, their drug loading capacity is constrained by their small pore size, and a further improvement in their drug capacity is needed. In this work, we report an effective and green structural modification strategy to improve drug loading capacity for Fe-based MOFs. Our strategy is to grow MIL-100 (Fe) on carboxylate-terminated polystyrene (PS-COOH) via a sustainable route, which creates a large inner cavity as well as exposure to more functional groups that benefit drug loading capacity. We employ the scanning electron microscope and transmission electron microscope to confirm the hollow structure of MIL-100 (Fe). Up to 30% of drug loading capacity has been demonstrated in our study. We also conduct cell viability tests to investigate its therapeutic effects on breast cancer cells (MDA-MB-231). Confocal laser scanning microscopy imaging confirms cellular uptake and mitochondrial targeting function of doxorubicin-loaded H-M (DOX@H-M) nanoparticles. JC-1 staining of cancer cells reveals a significant change in the mitochondrial membrane potential, indicating the mitochondrial dysfunction and apoptosis of tumor cells. Our study paves the way for the facile synthesis of hollow structural MOFs and demonstrates the potential of applying Fe-based MOFs in breast cancer treatment.


Assuntos
Estruturas Metalorgânicas , Nanopartículas , Doxorrubicina/farmacologia , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Mitocôndrias
19.
Small ; 17(47): e2104125, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34655163

RESUMO

Oxygen evolution reaction (OER) is critical for optimizing renewable energy systems, including metal-air batteries and water electrolysis. One major challenge for OER is to develop durable and cost-effective electrocatalysts with high catalytic performance. Herein, a controllable ion-exchange method to synthesize amorphous zinc/cobalt-iron hydroxide-based hollow nanowall arrays (A-Zn/Co-Fe HNAs) derived from bimetallic metal-organic frameworks (MOFs) on carbon cloth is reported. The amorphous characteristic enables the presented materials with more electrocatalytic sites and short diffusion paths for rapid access to the electrolyte, achieving efficient charge transfer for OER. The optimized nanostructure of A-Zn/Co-Fe HNAs via tuning the amount of iron sulfate in the reaction solution delivers a low overpotential of 226 mV to reach a current density of 10 mA cm-2 with a small Tafel slope of 37.81 mV dec-1 while exhibiting high durability at varied current densities over 80 h. The remarkable electrochemical performance can be attributed to the synergistic effect from chemical elements of Zn, Co-Fe, and a robust hollow structure. This simple method of fabricating bimetallic-MOF-derived amorphous Zn/Co-Fe HNAs on carbon cloth can be applied as a practical platform for other OER electrocatalysts.


Assuntos
Ferro , Oxigênio , Cobalto , Troca Iônica , Zinco
20.
Macromol Rapid Commun ; 42(12): e2100111, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33871122

RESUMO

An amphiphilic peptide dendrimer conjugated with gemcitabine (GEM), PEGylated dendron-Gly-Phe-Leu-Gly-GEM (PEGylated dendron-GFLG-GEM), is developed as a nano-prodrug for breast cancer therapy. The self-assembled behavior is observed under a transmission electron microscopy and dynamic light scattering. The negatively charged surface and hydrodynamic size of the amphiphilic nanosized prodrug supported that the prodrug can maintain the stability of GEM during circulation and accumulate in the tumor tissue. Drug release assays are conducted to monitor the release of GEM from this nanodrug delivery system in response to the tumor microenvironment, and these assays confirm that GEM released from the nanocarrier is identical to free GEM. The GEM prodrug can prevent proliferation of tumor cells. The therapeutic effect against breast cancer is systematically investigated using an in vivo animal model. Immunohistochemical results are aligned with the significantly enhanced anticancer efficacy of GEM released from the prodrug. This self-assembled amphiphilic drug delivery nanocarrier may broaden the application for GEM and other anticancer agents for breast cancer chemotherapy.


Assuntos
Dendrímeros , Nanopartículas , Neoplasias , Pró-Fármacos , Animais , Linhagem Celular Tumoral , Desoxicitidina/análogos & derivados , Peptídeos , Polietilenoglicóis , Pró-Fármacos/farmacologia , Gencitabina
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