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1.
Theranostics ; 11(19): 9415-9430, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646378

RESUMO

The feasibility of personalized medicine for cancer treatment is largely hampered by costly, labor-intensive and time-consuming models for drug discovery. Herein, establishing new pre-clinical models to tackle these issues for personalized medicine is urgently demanded. Methods: We established a three-dimensional tumor slice culture (3D-TSC) platform incorporating label-free techniques for time-course experiments to predict anti-cancer drug efficacy and validated the 3D-TSC model by multiphoton fluorescence microscopy, RNA sequence analysis, histochemical and histological analysis. Results: Using time-lapse imaging of the apoptotic reporter sensor C3 (C3), we performed cell-based high-throughput drug screening and shortlisted high-efficacy drugs to screen murine and human 3D-TSCs, which validate effective candidates within 7 days of surgery. Histological and RNA sequence analyses demonstrated that 3D-TSCs accurately preserved immune components of the original tumor, which enables the successful achievement of immune checkpoint blockade assays with antibodies against PD-1 and/or PD-L1. Label-free multiphoton fluorescence imaging revealed that 3D-TSCs exhibit lipofuscin autofluorescence features in the time-course monitoring of drug response and efficacy. Conclusion: This technology accelerates precision anti-cancer therapy by providing a cheap, fast, and easy platform for anti-cancer drug discovery.

2.
Adv Sci (Weinh) ; : e2101176, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34605222

RESUMO

Most breast cancers at an advanced stage exhibit an aggressive nature, and there is a lack of effective anticancer options. Herein, the development of patient-derived organoids (PDOs) is described as a real-time platform to explore the feasibility of tailored treatment for refractory breast cancers. PDOs are successfully generated from breast cancer tissues, including heavily treated specimens. The microtubule-targeting drug-sensitive response signatures of PDOs predict improved distant relapse-free survival for invasive breast cancers treated with adjuvant chemotherapy. It is further demonstrated that PDO pharmaco-phenotyping reflects the previous treatment responses of the corresponding patients. Finally, as clinical case studies, all patients who receive at least one drug predicate to be sensitive by PDOs achieve good responses. Altogether, the PDO model is developed as an effective platform for evaluating patient-specific drug sensitivity in vitro, which can guide personal treatment decisions for breast cancer patients at terminal stage.

3.
Bioresour Technol ; 342: 126026, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34598072

RESUMO

It is challenging to regenerate enzyme carriers when covalently immobilized enzymes suffered from inactivation during continuous operations. Hence, it is urgent to develop a facile strategy to immobilize enzymes reversibly. Herein, the non-covalent interaction between protein and carbohydrate was used to adsorb and desorb enzymes reversibly. Laccase was immobilized onto glycopolymer microspheres via protein-carbohydrate interaction using lectins as the intermediates. The enzyme loading and immobilization yield were up to 49 mg/g and 77.1% with highly expressed activity of 107.9 U/mg. The immobilized laccase exhibited enhanced pH stability and high activity in catalyzing the biodegradation of paracetamol. During ten successive recoveries, the immobilized laccases could be recycled while maintaining relatively high enzyme activity. The glycopolymer microspheres could be efficiently regenerated by elution with an aqueous solution of mannose or acid for further enzyme immobilization. This glycopolymer microspheres has excellent potential to act as reusable carriers for the non-covalent immobilization of different enzymes.

4.
Oncogene ; 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34611310

RESUMO

Androgen receptor (AR) plays a central role in driving prostate cancer (PCa) progression. How AR promotes this process is still not completely clear. Herein, we used single-cell transcriptome analysis to reconstruct the transcriptional network of AR in PCa. Our work shows AR directly regulates a set of signature genes in the ER-to-Golgi protein vesicle-mediated transport pathway. The expression of these genes is required for maximum androgen-dependent ER-to-Golgi trafficking, cell growth, and survival. Our analyses also reveal the signature genes are associated with PCa progression and prognosis. Moreover, we find inhibition of the ER-to-Golgi transport process with a small molecule enhanced antiandrogen-mediated tumor suppression of hormone-sensitive and insensitive PCa. Finally, we demonstrate AR collaborates with CREB3L2 in mediating ER-to-Golgi trafficking in PCa. In summary, our findings uncover a critical role for dysregulation of ER-to-Golgi trafficking expression and function in PCa progression, provide detailed mechanistic insights for how AR tightly controls this process, and highlight the prospect of targeting the ER-to-Golgi pathway as a therapeutic strategy for advanced PCa.

5.
Adv Sci (Weinh) ; : e2100974, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34514747

RESUMO

Fibroblast growth factor receptor 2 (FGFR2) is a membrane-spanning tyrosine kinase that mediates FGF signaling. Various FGFR2 alterations are detected in breast cancer, yet it remains unclear if activation of FGFR2 signaling initiates tumor formation. In an attempt to answer this question, a mouse model berrying an activation mutation of FGFR2 (FGFR2-S252W) in the mammary gland is generated. It is found that FGF/FGFR2 signaling drives the development of triple-negative breast cancer accompanied by epithelial-mesenchymal transition that is regulated by FGFR2-STAT3 signaling. It is demonstrated that FGFR2 suppresses BRCA1 via the ERK-YY1 axis and promotes tumor progression. BRCA1 knockout in the mammary gland of the FGFR2-S252W mice significantly accelerated tumorigenesis. It is also shown that FGFR2 positively regulates PD-L1 and that a combination of FGFR2 inhibition and immune checkpoint blockade kills cancer cells. These data suggest that the mouse models mimic human breast cancers and can be used to identify actionable therapeutic targets.

6.
Oncogene ; 40(41): 6023-6033, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34433910

RESUMO

Sirtuin-1 (SIRT1) is involved in various metabolic pathways, including fatty acid synthesis and gluconeogenesis in the liver. However, its role in initiation and progression of liver cancer remains unclear. Studying Sirt1 liver-specific knockout (LKO) mice in combination with diethylnitrosamine (DEN) treatment, we demonstrated that loss of Sirt1 rendered mice resistant to DEN-induced hepatocellular carcinoma (HCC) development. RNA-seq revealed that livers from LKO mice exhibited an enrichment in glutathione metabolism eight months after DEN challenge. Sirt1 deficiency elevated the expression of glutathione-s-transferase family genes by increasing the level of Nrf2, a key regulator of glutathione metabolism. Hence, LKO livers displayed a reductive environment with an increased ratio of GSH to GSSG and an elevated GSH level. Furthermore, using CRISPR knockout techniques, we confirmed that the impairment of HCC formation in LKO mice is mainly dependent on NRF2 signaling. Meanwhile, HCC induced by DEN could be blocked by the administration of N-acetyl cysteine (NAC) when administered one month after DEN challenge. However, NAC treatment starting five months after DEN injection was not able to prevent tumor development. In conclusion, our findings indicate that a reductive environment orchestrated by glutathione metabolism at an early stage can prevent the initiation of HCC.

7.
Nat Commun ; 12(1): 4755, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34362890

RESUMO

Some specific chemotherapeutic drugs are able to enhance tumor immunogenicity and facilitate antitumor immunity by inducing immunogenic cell death (ICD). However, tumor immunosuppression induced by the adenosine pathway hampers this effect. In this study, E-selectin-modified thermal-sensitive micelles are designed to co-deliver a chemotherapeutic drug (doxorubicin, DOX) and an A2A adenosine receptor antagonist (SCH 58261), which simultaneously exhibit chemo-immunotherapeutic effects when applied with microwave irradiation. After intravenous injection, the fabricated micelles effectively adhere to the surface of leukocytes in peripheral blood mediated by E-selectin, and thereby hitchhiking with leukocytes to achieve a higher accumulation at the tumor site. Further, local microwave irradiation is applied to induce hyperthermia and accelerates the release rate of drugs from micelles. Rapidly released DOX induces tumor ICD and elicits tumor-specific immunity, while SCH 58261 alleviates immunosuppression caused by the adenosine pathway, further enhancing DOX-induced antitumor immunity. In conclusion, this study presents a strategy to increase the tumor accumulation of drugs by hitchhiking with leukocytes, and the synergistic strategy of chemo-immunotherapy not only effectively arrested primary tumor growth, but also exhibited superior effects in terms of antimetastasis, antirecurrence and antirechallenge.


Assuntos
Tratamento Farmacológico , Imunoterapia , Leucócitos/efeitos dos fármacos , Micelas , Neoplasias/terapia , Animais , Doxorrubicina/farmacologia , Portadores de Fármacos/administração & dosagem , Liberação Controlada de Fármacos , Feminino , Hipertermia/terapia , Imunidade , Camundongos , Camundongos Endogâmicos BALB C , Micro-Ondas/uso terapêutico , Fototerapia
8.
J Int Med Res ; 49(8): 3000605211031682, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34369190

RESUMO

Infected cavitating pulmonary infarction is a rare complication of pulmonary embolism with a high mortality rate. Surgical excision for this complication has been used in past decades. Abrupt cavitation and a large oval-shaped lung abscess caused by acute thromboembolic pulmonary infarction during anticoagulation are rare. We present a 70-year-old man who suffered from pleuritic pain and breathlessness, accompanied by nausea and vomiting for 1 day. A physical examination showed tachycardia and tachypnea with moist rales in the left upper chest. High D-dimer levels, leukocytosis, respiratory failure and left upper lobe consolidation were found on plain computed tomography (CT). CT pulmonary angiography was performed 2 days after the previous CT scan because pulmonary embolism was suspected. This scan showed emboli in the main, right upper, middle, lower and left upper pulmonary arteries with deteriorated left upper lobe consolidation and cavitation. Thromboembolic pulmonary infarction and an abscess were diagnosed. Enoxaparin 60 mg was administered every 12 hours for 10 days, followed by rivaroxaban, antibiotics and drainage of the hydrothorax. The patient improved after the strategy of non-surgical treatment and was discharged approximately 1 month later. The patient had an uneventful course during rivaroxaban 20 mg once daily for 1 year.


Assuntos
Abscesso Pulmonar , Embolia Pulmonar , Infarto Pulmonar , Tromboembolia , Idoso , Humanos , Abscesso Pulmonar/complicações , Abscesso Pulmonar/diagnóstico por imagem , Masculino , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/cirurgia , Embolia Pulmonar/complicações , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/tratamento farmacológico , Infarto Pulmonar/complicações , Infarto Pulmonar/diagnóstico por imagem
9.
Mol Pharm ; 18(9): 3206-3222, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34337953

RESUMO

Kidney diseases, including acute kidney injury (AKI) and chronic kidney disease (CKD), have become a global public health concern associated with high morbidity, mortality, and healthcare costs. However, at present, very few effective and specific drug therapies are available, owing to the poor therapeutic efficacy and systemic side effects. Kidney-targeted drug delivery, as a potential strategy for solving these problems, has received great attention in the fields of AKI and CKD in recent years. Here, we review the literature on renal targeted, more specifically, renal cell-targeted formulations of AKI and CKD that offered biodistribution data. First, we provide a broad overview of the unique structural characteristics and injured cells of acute and chronic injured kidneys. We then separately summarize literature examples of renal targeted formulations according to the difference of target cells and elaborate on the appropriate formulation design criteria for AKI and CKD. Finally, we propose a hypothetic strategy to improve the renal accumulation of glomerular cell-targeted formulation by escaping the uptake of the reticuloendothelial system and provide some perspectives for future studies.

10.
Int J Nanomedicine ; 16: 4693-4712, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34267518

RESUMO

Benefiting from the rapid development of nanotechnology, photodynamic therapy (PDT) is arising as a novel non-invasive clinical treatment for specific cancers, which exerts direct efficacy in destroying primary tumors by generating excessive cytotoxic reactive oxygen species (ROS). Notably, PDT-induced cell death is related to T cell-mediated antitumor immune responses through induction of immunogenic cell death (ICD). However, ICD elicited via PDT is not strong enough and is limited by immunosuppressive tumor microenvironment (ITM). Therefore, it is necessary to improve PDT efficacy through enhancing ICD with the combination of synergistic tumor therapies. Herein, the recent progress of nanomaterials-based PDT combined with chemotherapy, photothermal therapy, radiotherapy, and immunotherapy, employing ICD-boosted treatments is reviewed. An outlook about the future application in clinics of nanomaterials-based PDT strategies is also mentioned.


Assuntos
Morte Celular Imunogênica/efeitos dos fármacos , Nanomedicina/métodos , Nanoestruturas , Fotoquimioterapia/métodos , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Neoplasias/patologia
11.
Artigo em Inglês | MEDLINE | ID: mdl-34219038

RESUMO

As an active glycoprotein with high nutritional value, lactoferrin is widely used in food and medical treatment. Therefore, it is very important to establish an accurate and efficient detection method for lactoferrin. At present, the detection of lactoferrin in milk faces many challenges, such as low separation degree and poor parallelism. To address this issue, we developed an aptamer affinity column (AAC) for purification and enrichment of lactoferrin in milk. The column was prepared by covalent conjugation of an amino-modified aptamer with NHS-activated Sepharose. The washing buffer type (0.01 mol/L phosphate buffer) and volume (10 mL) and the sodium chlorideconcentration (1 mol/L) in the elution buffer were optimized for the AAC method. The performance of the AAC was then evaluated in terms of the column capacity, specificity, stability, and reusability. The column capacity was 500 ± 13.7 µg and the column could be reused up to ten times with a large loss in performance. The AAC method combined with high-performance liquid chromatography gave excellent linearity over a wide range, good sensitivity with a limit of detection of 3 µg/mL, and acceptable recoveries for different concentrations of lactoferrin spiked in real raw milk samples from cattle. Finally, the AAC was successfully applied to analyze lactoferrin in milk. This method could be applied to routine analysis of samples for lactoferrin in testing laboratories and dairy factories.


Assuntos
Cromatografia de Afinidade/métodos , Lactoferrina , Leite/química , Animais , Aptâmeros de Nucleotídeos/química , Bovinos , Cromatografia Líquida de Alta Pressão/métodos , Lactoferrina/análise , Lactoferrina/química , Lactoferrina/isolamento & purificação , Limite de Detecção , Modelos Lineares , Reprodutibilidade dos Testes
12.
J Control Release ; 337: 90-104, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34274385

RESUMO

Photodynamic therapy (PDT) and chemotherapy show clinical promise in destroying orthotopic tumors but are insufficient against abscopal metastases. The research reports the combined application of an anti-CD73 antibody and chemo-PDT to synergistically amplify the anti-metastatic effects of T cell-mediated antitumor immunity. The cancer cell membrane (CM)-cloaked upconversion nanoparticles, integrating rose bengal (RB) and the reactive oxygen species (ROS)-sensitive polymer polyethylene glycol-thioketal-doxorubicin (PEG-TK-DOX, i.e., PTD), are tailored for near-infrared (NIR)-triggered chemo-PDT. CM camouflage enables nanoparticles' excellent tumor-targeting abilities and immune escape from macrophages. The combination of PDT and chemotherapy presents strong synergistic antitumor efficacy and synchronously causes a series of immunogenic cell death (ICD), leading to tumor-specific immunity. The anti-CD73 antibody prevents the immunosuppression phenomenon in tumors by blocking the adenosine pathway, and it is emerging as a sufficient immune checkpoint blockade when combined with ICD-elicited tumor therapies. As cancer membrane camouflaged nanoparticles CM@UCNP-RB/PTD combined with anti-CD73 antibodies, synergistic efficacy of chemotherapy and PDT not only destroys the orthotopic tumors by DOX and cytotoxic ROS but also prevents abscopal tumor metastasis via inducing systemic cytotoxic T cell responses with CD73 blockade. This strategy is promising in curing metastatic triple-negative breast cancer in preclinical research.

13.
J Hazard Mater ; 419: 126503, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-34214857

RESUMO

Excess boron in water could result in a critical hazard to plants and humans. Traditional treatment approaches cannot efficiently remove boron from water, especially during seawater desalination using reverse osmosis technology. Achieving satisfactory adsorption capacity and rate for boron remains an unmet goal for decades. Herein, we report cellulose-derived polyols as high-performance adsorbents that can rapidly remove boron and organic pollutants from water. Cellulose-derived polyols were synthesized from saccharides and cellulose via controlled radical polymerization and click reaction. Remarkably, CA@NMDG can adsorb boron with an astonishing capacity of ~34 mg g-1 in 10 min, which surpasses all those cellulose-based materials reported thus far, meanwhile, much faster than those of commercial adsorption resin. Moreover, cellulose-derived polyols also showed high removal efficiencies (70-98% in several minutes) toward certain organic pollutants, including Congo red and Reactive Blue 19. The water-insoluble characteristic of cellulose-derived polyols is advantageous to be separated from the treated sewage after adsorption for reuse. This work provides a novel insight into the fabrication of safe, fast, and high-capacity cellulose adsorbents for water purification.


Assuntos
Poluentes Ambientais , Poluentes Químicos da Água , Purificação da Água , Adsorção , Boro , Celulose , Humanos , Polímeros , Água , Poluentes Químicos da Água/análise
14.
J Cell Mol Med ; 25(11): 5295-5304, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33960640

RESUMO

Acute myeloid leukaemia is a complex, highly aggressive hematopoietic disorder. Currently, in spite of great advances in radiotherapy and chemotherapy, the prognosis for AML patients with initial treatment failure is still poor. Therefore, the need for novel and efficient therapies to improve AML treatment outcome has become desperately urgent. In this study, we identified the expression of ZEB1 (a transcription factor) and focused on its possible role and mechanisms in the progression of AML. According to the data provided by the Gene Expression Profiling Interactive Analysis (GEPIA), high expression of ZEB1 closely correlates with poor prognosis in AML patients. Additionally, the overexpression of ZEB1 was observed in both AML patients and cell lines. Further functional experiments showed that ZEB1 depletion can induce AML differentiation and inhibit AML proliferation in vitro and in vivo. Moreover, ZEB1 expression was negatively correlated with tumour suppressor P53 expression and ZEB1 can directly bind to P53. Our results also revealed that ZEB1 can regulate PTEN/PI3K/AKT signalling pathway. The inhibitory effect of ZEB1 silencing on PTEN/PI3K/AKT signalling pathway could be significantly reversed by P53 small interfering RNA treatment. Overall, the present data indicated that ZEB1 may be a promising therapeutic target for AML treatment or a potential biomarker for diagnosis and prognosis.


Assuntos
Biomarcadores Tumorais/metabolismo , Leucemia Mieloide Aguda/tratamento farmacológico , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo , Animais , Apoptose , Biomarcadores Tumorais/genética , Ciclo Celular , Diferenciação Celular , Proliferação de Células , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , PTEN Fosfo-Hidrolase/genética , Fosfatidilinositol 3-Quinases/genética , Prognóstico , Proteínas Proto-Oncogênicas c-akt/genética , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética
15.
J Nanobiotechnology ; 19(1): 132, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33971910

RESUMO

Molecular imaging technology enables us to observe the physiological or pathological processes in living tissue at the molecular level to accurately diagnose diseases at an early stage. Optical imaging can be employed to achieve the dynamic monitoring of tissue and pathological processes and has promising applications in biomedicine. The traditional first near-infrared (NIR-I) window (NIR-I, range from 700 to 900 nm) imaging technique has been available for more than two decades and has been extensively utilized in clinical diagnosis, treatment and scientific research. Compared with NIR-I, the second NIR window optical imaging (NIR-II, range from 1000 to 1700 nm) technology has low autofluorescence, a high signal-to-noise ratio, a high tissue penetration depth and a large Stokes shift. Recently, this technology has attracted significant attention and has also become a heavily researched topic in biomedicine. In this study, the optical characteristics of different fluorescence nanoprobes and the latest reports regarding the application of NIR-II nanoprobes in different biological tissues will be described. Furthermore, the existing problems and future application perspectives of NIR-II optical imaging probes will also be discussed.

16.
Nat Commun ; 12(1): 3046, 2021 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-34031426

RESUMO

Nasopharyngeal carcinoma (NPC) is a malignant head and neck cancer type with high morbidity in Southeast Asia, however the pathogenic mechanism of this disease is poorly understood. Using integrative pharmacogenomics, we find that NPC subtypes maintain distinct molecular features, drug responsiveness, and graded radiation sensitivity. The epithelial carcinoma (EC) subtype is characterized by activations of microtubule polymerization and defective mitotic spindle checkpoint related genes, whereas sarcomatoid carcinoma (SC) and mixed sarcomatoid-epithelial carcinoma (MSEC) subtypes exhibit enriched epithelial-mesenchymal transition (EMT) and invasion promoting genes, which are well correlated with their morphological features. Furthermore, patient-derived organoid (PDO)-based drug test identifies potential subtype-specific treatment regimens, in that SC and MSEC subtypes are sensitive to microtubule inhibitors, whereas EC subtype is more responsive to EGFR inhibitors, which is synergistically enhanced by combining with radiotherapy. Through combinational chemoradiotherapy (CRT) screening, effective CRT regimens are also suggested for patients showing less sensitivity to radiation. Altogether, our study provides an example of applying integrative pharmacogenomics to establish a personalized precision oncology for NPC subtype-guided therapies.


Assuntos
Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/genética , Farmacogenética/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Transição Epitelial-Mesenquimal , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Técnicas de Inativação de Genes , Humanos , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Medicina de Precisão , Transcriptoma , Sequenciamento Completo do Exoma
17.
Sensors (Basel) ; 21(7)2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33807129

RESUMO

This paper is concerned with relative localization-based optimal area coverage placement using multiple unmanned aerial vehicles (UAVs). It is assumed that only one of the UAVs has its global position information before performing the area coverage task and that ranging measurements can be obtained among the UAVs by using ultra-wide band (UWB) sensors. In this case, multi-UAV relative localization and cooperative coverage control have to be run simultaneously, which is a quite challenging task. In this paper, we propose a single-landmark-based relative localization algorithm, combined with a distributed coverage control law. At the same time, the optimal multi-UAV placement problem was formulated as a quadratic programming problem by compromising between optimal relative localization and optimal coverage control and was solved by using Sequential Quadratic Programming (SQP) algorithms. Simulation results show that our proposed method can guarantee that a team of UAVs can efficiently localize themselves in a cooperative manner and, at the same time, complete the area coverage task.

18.
Expert Rev Vaccines ; 20(5): 545-557, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33769185

RESUMO

INTRODUCTION: Cancer remains a major source of disease burden worldwide. Although cancer vaccines have been developed, most currently available cancer vaccines have limited therapeutic efficacy. Recent research using novel sequencing and bioinformatic tools has led scientists to realize that each tumor harbors a unique set of genetic mutations that can manifest as tumor-specific neoantigens. Therefore, it would be useful to develop personalized cancer vaccines that target neoantigens, which might improve the efficacy of these cancer treatments. AREAS COVERED: This review covers cancer vaccine development and the emerging field of personalized cancer vaccines, with a discussion of future clinical trials for this promising treatment strategy. EXPERT OPINION: Developing vaccines to treat tumors is one of the most promising and exciting fields in cancer research. However, cancer vaccines have shown limited efficacy in clinical trials for several decades, which may be related to the unique and complex processes underlying tumor development and progression. Recent studies have indicated that tumors express highly specific neoantigens, which are distinct from self-antigens. Thus, developing cancer vaccines that target these tumor-specific neoantigens is a promising strategy for developing personalized cancer vaccines.

19.
J Nanobiotechnology ; 19(1): 76, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33731140

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis. Magnetic resonance imaging (MRI) is one of the most effective imaging methods for the early diagnosis of HCC. However, the current MR contrast agents are still facing challenges in the early diagnosis of HCC due to their relatively low sensitivity and biosafety. Thus, the development of effective MR agents is highly needed for the early diagnosis of HCC. RESULTS: Herein, we fabricated an HCC-targeted nanocomplexes containing SPIO-loaded mesoporous polydopamine (MPDA@SPIO), sialic acid (SA)-modified polyethyleneimine (SA-PEI), and alpha-fetoprotein regulated ferritin gene (AFP-Fth) which was developed for the early diagnosis of HCC. It was found that the prepared nanocomplexes (MPDA@SPIO/SA-PEI/AFP-Fth) has an excellent biocompatibility towards the liver cells. In vivo and in vivo studies revealed that the transfection of AFP-Fth gene in hepatic cells significantly upregulated the expression level of ferritin, thereby resulting in an enhanced contrast on T2-weighted images via the formed endogenous MR contrast. CONCLUSIONS: The results suggested that MPDA@SPIO/SA-PEI/AFP-Fth had a superior ability to enhance the MR contrast of T2-weighted images of tumor region than the other preparations, which was due to its HCC-targeted ability and the combined T2 contrast effect of endogenous ferritin and exogenous SPIO. Our study proved that MPDA@SPIO/SA-PEI/AFP-Fth nanocomplexes could be used as an effective MR contrast agent to detect HCC in the early stage.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Compostos Férricos/química , Ferritinas/genética , Indóis/química , Neoplasias Hepáticas/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Ácido N-Acetilneuramínico/química , Polímeros/química , Animais , Carcinoma Hepatocelular/patologia , Modelos Animais de Doenças , Células Hep G2 , Humanos , Ferro , Fígado/diagnóstico por imagem , Fígado/patologia , Neoplasias Hepáticas/patologia , Nanopartículas de Magnetita/química , Camundongos , Camundongos Endogâmicos BALB C , Transfecção , alfa-Fetoproteínas/metabolismo
20.
Int J Nanomedicine ; 16: 1435-1456, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33654395

RESUMO

Cancer immunotherapy is a promising treatment strategy that aims to strengthen immune responses against cancer. However, the low immunogenicity of tumor cells and inhibition of effector T cells in the tumor immunosuppressive microenvironment remain two major challenges. Immunogenic cell death (ICD) inducers not only directly kill cancer cells but also increase the tumor immunogenicity and induce antitumor immune responses. Immune checkpoint inhibitors can alleviate the inhibition of immune cells. Significantly, the combination of ICD inducers and immune checkpoint inhibitors elicits a remarkable antitumor effect. Nanoparticles confer the ability to modulate systemic biodistribution and achieve targeted accumulation of administered therapeutic agents, thereby facilitating the clinical translation of immunotherapies based on ICD inducers in a safe and effective manner. In this review, we summarize the nanoparticle-based chemical and physical cues that induce effective tumor ICD and elicit an antitumor immune response. In particular, combination of ICD inducers with immune checkpoint inhibitors can further reverse immunosuppression and prevent tumor metastasis and recurrence. An overview of the future challenges and prospects is also provided.


Assuntos
Inibidores de Checkpoint Imunológico/uso terapêutico , Morte Celular Imunogênica , Imunoterapia , Nanopartículas/química , Neoplasias/terapia , Animais , Terapia Combinada , Humanos , Neoplasias/tratamento farmacológico
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