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1.
J Nanobiotechnology ; 22(1): 156, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589867

RESUMO

Immunotherapy has revolutionized the treatment of cancer. However, its efficacy remains to be optimized. There are at least two major challenges in effectively eradicating cancer cells by immunotherapy. Firstly, cancer cells evade immune cell killing by down-regulating cell surface immune sensors. Secondly, immune cell dysfunction impairs their ability to execute anti-cancer functions. Radiotherapy, one of the cornerstones of cancer treatment, has the potential to enhance the immunogenicity of cancer cells and trigger an anti-tumor immune response. Inspired by this, we fabricate biofunctionalized liposome-like nanovesicles (BLNs) by exposing irradiated-cancer cells to ethanol, of which ethanol serves as a surfactant, inducing cancer cells pyroptosis-like cell death and facilitating nanovesicles shedding from cancer cell membrane. These BLNs are meticulously designed to disrupt both of the aforementioned mechanisms. On one hand, BLNs up-regulate the expression of calreticulin, an "eat me" signal on the surface of cancer cells, thus promoting macrophage phagocytosis of cancer cells. Additionally, BLNs are able to reprogram M2-like macrophages into an anti-cancer M1-like phenotype. Using a mouse model of malignant pleural effusion (MPE), an advanced-stage and immunotherapy-resistant cancer model, we demonstrate that BLNs significantly increase T cell infiltration and exhibit an ablative effect against MPE. When combined with PD-1 inhibitor (α-PD-1), we achieve a remarkable 63.6% cure rate (7 out of 11) among mice with MPE, while also inducing immunological memory effects. This work therefore introduces a unique strategy for overcoming immunotherapy resistance.


Assuntos
Lipossomos , Neoplasias , Humanos , Lipossomos/metabolismo , Neoplasias/radioterapia , Neoplasias/metabolismo , Macrófagos/metabolismo , Imunoterapia , Etanol/metabolismo , Linhagem Celular Tumoral
2.
Molecules ; 21(9)2016 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-27618001

RESUMO

Poly(N-isopropylacrylamide) (PNIPAM)-based polymers and gels are widely known and studied for their thermoresponsive property. In the biomaterials category, they are regarded as a potential cell culture substrate, not only because of their biocompatibility, but also their special character of allowing controlled detachment of cells via temperature stimulus. Previous research about PNIPAM-based substrates mostly concentrated on their effects in cell adhesion and proliferation. In this study, however, we investigate the influence of the PNIPAM-based substrate on the differentiation capacity of stem cells. Especially, we choose P(NIPAM-AA) microgels as a culture dish coating and mesenchymal stem cells (MSCs) are cultured on top of the microgels. Interestingly, we find that the morphology of MSCs changes remarkably on a microgel-coated surface, from the original spindle form to a more stretched and elongated cell shape. Accompanied by the alternation in morphology, the expression of several osteogenesis-related genes is elevated even without inducing factors. In the presence of full osteogenic medium, MSCs on a microgel substrate show an enhancement in the expression level of osteopontin and alizarin red staining signals, indicating the physical property of substrate has a direct effect on MSCs differentiation.


Assuntos
Resinas Acrílicas/química , Técnicas de Cultura de Células/métodos , Diferenciação Celular , Células-Tronco Mesenquimais/metabolismo , Animais , Células Cultivadas , Células-Tronco Mesenquimais/citologia , Camundongos
3.
Biomater Sci ; 9(19): 6381-6390, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34582527

RESUMO

Malignant pleural effusion (MPE) and malignant ascites (MA), which are common but serious conditions caused by malignancies, are related to poor quality of life and high mortality. Current treatments, including therapeutic thoracentesis and indwelling pleural catheters or paracentesis and catheter drainage, are largely palliative. An effective treatment is urgently needed. MPE and MA are excellent candidates for intratumoural injections that have direct contact with tumour cells and kill tumour cells more effectively and efficiently with fewer side effects, and the fluid environment of MPE and MA can provide a homogeneous area for drug distribution. The immunosuppressive environments within the pleural and peritoneal cavities suggest the feasibility of local immunotherapy. In this review, we introduce the current management of MPE and MA, discuss the latest advances and challenges in utilizing local biomaterial-assisted antitumour therapies for the treatment of MPE and MA, and discuss further opportunities in this field.


Assuntos
Derrame Pleural Maligno , Pleurodese , Materiais Biocompatíveis , Humanos , Imunoterapia , Derrame Pleural Maligno/terapia , Qualidade de Vida
4.
Thorac Cancer ; 10(6): 1369-1377, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31017731

RESUMO

BACKGROUND: This study evaluated the safety and efficacy of localized injection of polyethylene glycol (PEG)-hyperbranched polyethyleneimine (PEI)-EGFR-small interfering RNA (siRNA) nanocomposites as a treatment for residual lung cancer after incomplete microwave ablation (MWA). METHODS: Human lung cancer cell lines with high and low EGFR expression were selected for the study. The effects of PEG-PEI-EGFR-siRNA nanocomposite transfection on the proliferation, migration, and apoptosis of lung cancer cells were verified. Sixteen healthy ICR mice were injected into the lung to test the biological safety of the nanocomposites. In addition, 24 subcutaneous xenograft BALB/C nude mice with high EGFR expression were separated into four groups and then treated with an intratumoral injection of PEG-PEI-EGFR-siRNA, PEG-PEI-normal control (NC)-siRNA, PEG-PEI-EGFR-siRNA after MWA, or PEG-PEI-NC-siRNA after MWA. Tumor growth, pathological changes, and EGFR expression in each group were observed. RESULTS: PEG-PEI-EGFR-siRNA nanocomposites were transfected to HCC 827 cells showing high EGFR expression and to H23 cells showing low EGFR expression. In HCC827 cells, downregulation of EGFR gene expression reduced cell proliferation, invasion, and migration, whereas cell apoptosis increased. In contrast, in H23 cells, no significant differences in those parameters were detected. No acute toxicity occurred in the ICR mice during the biosafety test. Localized injection of PEG-PEI-EGFR-siRNA nanocomposites significantly inhibited the growth of human lung xenografts in mice and the growth of residual tumors after MWA. CONCLUSION: PEG-PEI-EGFR-siRNA nanocomposites may be a supplemental therapy strategy to treat residual lung cancer after incomplete MWA.


Assuntos
Polietilenoimina/química , Terapêutica com RNAi/métodos , Ablação por Radiofrequência/métodos , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Terapia Combinada , Receptores ErbB/antagonistas & inibidores , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Nanocompostos , Neoplasia Residual , Polietilenoglicóis/química , Interferência de RNA , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Biomater Sci ; 7(8): 3158-3164, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31232421

RESUMO

Indocyanine green (ICG) is a clinically-approved near infrared (NIR) dye used for optical imaging. The dye is only slightly soluble in water and is prone to aggregation in saline solutions, so that alternative formulations can improve photophysical performance. Numerous nanoscale formulations of ICG have been described in the literature, but we sought to develop an approach that does not require additional purification steps. Pre-formed liposomes incorporating 45 mol% of the cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) rapidly bind ICG, resulting in enhanced NIR optical properties. ICG binding is dependent on the amount of DOTAP incorporated in the liposomes. A dye-to-lipid mass ratio of [0.5 : 25] is sufficient for full complexation, without additional purification steps following mixing. NIR absorption, fluorescence intensity, and photoacoustic signals are increased for the liposome-bound dye. Not only is the optical character enhanced by simple mixing of ICG with liposomes, but retention in 4T1 mammary tumors is observed following intratumor injection, as assessed by fluorescence and photoacoustic imaging. Subsequent photothermal therapy with 808 nm laser irradiation is effective and results in tumor ablation without regrowth for at least 30 days. Thus, ICG optical properties and photothermal ablation outcomes can be improved by mixing the dye with pre-formed DOTAP liposomes in conditions that result in full dye-binding to the liposomes.


Assuntos
Técnicas de Ablação/métodos , Ácidos Graxos Monoinsaturados/química , Verde de Indocianina/química , Lipossomos/química , Neoplasias Mamárias Experimentais/terapia , Fenômenos Ópticos , Compostos de Amônio Quaternário/química , Animais , Feminino , Neoplasias Mamárias Experimentais/diagnóstico por imagem , Camundongos , Imagem Óptica , Fototerapia
6.
ACS Nano ; 12(4): 3295-3310, 2018 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-29558107

RESUMO

Immunosuppressive tumor microenvironments (TMEs) create tremendous obstacles for an effective cancer therapy. Herein, we developed a melittin-RADA32 hybrid peptide hydrogel loaded with doxorubicin (DOX) for a potent chemoimmunotherapy against melanoma through the active regulation of TMEs. The formed melittin-RADA32-DOX (MRD) hydrogel has an interweaving nanofiber structure and exhibits excellent biocompatibility, controlled drug release properties both in vitro and in vivo, and an enhanced killing effect to melanoma cells. A single-dose injection of MRD hydrogel retarded the growth of primary melanoma tumors by more than 95% due to loaded melittin and DOX, with concomitant recruitment of activated natural killer cells in the tumors. Furthermore, MRD hydrogel can activate dendritic cells of draining lymph nodes, specifically deplete M2-like tumor-associated macrophages (TAMs), and produce active, cytotoxic T cells to further defend the cells against remaining tumors, providing potent anticancer efficacy against subcutaneous and metastatic tumors in vivo. Multidose injection of MRD hydrogel eliminated 50% of the primary tumors and provided a strong immunological memory effect against tumor rechallenge after eradication of the initial tumors. Owing to its abilities to perform controlled drug release, regulate innate immune cells, deplete M2-like TAMs, direct anticancer and immune-stimulating capabilities, and reshape immunosuppressive TMEs, MRD hydrogel may serve as a powerful tool for anticancer applications.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacologia , Melanoma Experimental/terapia , Peptídeos/farmacologia , Neoplasias Cutâneas/terapia , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Humanos , Hidrogel de Polietilenoglicol-Dimetacrilato/administração & dosagem , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Imunoterapia , Melanoma Experimental/imunologia , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos C57BL , Peptídeos/administração & dosagem , Peptídeos/química , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Relação Estrutura-Atividade
7.
Biomaterials ; 120: 11-21, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28024231

RESUMO

Hydrogels prepared from poly(ethylene glycol) (PEG) are widely applied in tissue engineering, especially those derived from a combination of functional multi-arm star PEG and linear crosslinker, with an expectation to form a structurally ideal network. However, the poor mechanical strength still renders their further applications. Here we examined the relationship between the dynamics of the pre-gel solution and the mechanical property of the resultant hydrogel in a system consisting of 4-arm star PEG functionalized with vinyl sulfone and short dithiol crosslinker. A method to prepare mechanically strong hydrogel for cartilage tissue engineering is proposed. It is found that when gelation takes place at the overlap concentration, at which a slow relaxation mode just appears in dynamic light scattering (DLS), the resultant hydrogel has a local maximum compressive strength ∼20 MPa, while still keeps ultralow mass concentration and Young's modulus. Chondrocyte-laden hydrogel constructed under this condition was transplanted into the subcutaneous pocket and an osteochondral defect model in SCID mice. The in vivo results show that chondrocytes can proliferate and maintain their phenotypes in the hydrogel, with the production of abundant extracellular matrix (ECM) components, formation of typical chondrocyte lacunae structure and increase in Young's modulus over 12 weeks, as indicated by histological, immunohistochemistry, gene expression analyses and mechanical test. Moreover, newly formed hyaline cartilage was observed to be integrated with the host articular cartilage tissue in the defects injected with chondrocytes/hydrogel constructs. The results suggest that this hydrogel is a promising candidate scaffold for cartilage tissue engineering.


Assuntos
Cartilagem Articular/citologia , Cartilagem Articular/crescimento & desenvolvimento , Condrócitos/transplante , Hidrogéis/síntese química , Polietilenoglicóis/síntese química , Engenharia Tecidual/métodos , Animais , Células Cultivadas , Condrócitos/citologia , Condrócitos/fisiologia , Condrogênese/fisiologia , Força Compressiva , Módulo de Elasticidade , Dureza , Hidrogéis/administração & dosagem , Injeções , Masculino , Teste de Materiais , Camundongos , Camundongos SCID , Polietilenoglicóis/administração & dosagem , Estresse Mecânico , Resistência à Tração , Alicerces Teciduais , Viscosidade
8.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 27(1): 38-41, 2005 Feb.
Artigo em Zh | MEDLINE | ID: mdl-15782491

RESUMO

OBJECTIVE: To evaluate the efficacy of treating severe and chronic vertebral compressive fractures in the elderly with percutaneous vertebroplasty. METHODS: Sixteen patients who suffered from severe back pain and whose daily living was badly affected were retrospectively reviewed. The average age was 72.5 years, the average disease history was 19 months, and the average compressive rate of the affected vertebral bodies was 74.1%. RESULTS: Nineteen affected compressive vertebral bodies in 16 cases were treated with percutaneous vertebroplasty. All the procedures were successful without any complication. After 3.5-7 ml of cement was injected into the lesions, complete relief was achieved in 3 cases, remarkable relief was achieved in 11 cases, and improvement was observed in 2 cases. The scores of 6-point Behavioral Rating Scale and Activity of Daily Living (ADL) declined significantly after the treatment (P < 0.001). CONCLUSION: Percutaneous vertebroplasty can significantly improve the symptoms and quality of life in the elderly patients with severe and chronic vertebral compressive fractures.


Assuntos
Dor nas Costas/cirurgia , Cimentos Ósseos/uso terapêutico , Fraturas Espontâneas/cirurgia , Procedimentos Ortopédicos/métodos , Fraturas da Coluna Vertebral/cirurgia , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Feminino , Fraturas Espontâneas/etiologia , Humanos , Vértebras Lombares/cirurgia , Masculino , Osteoporose/complicações , Qualidade de Vida , Estudos Retrospectivos , Fraturas da Coluna Vertebral/etiologia , Vértebras Torácicas/cirurgia
9.
J Biomater Appl ; 29(9): 1272-83, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25361919

RESUMO

Osteoblastic differentiation of mesenchymal stem cells from bone marrow is an essential step for bone formation. The osteogenesis is normally induced by chemical mediators. Recent laboratory studies have revealed that mechanical properties of an extracellular matrix, typically hydrogels with different modules, also affect the fate of stem cells. The question is how to adjust their mechanical properties inside the body in biomedical applications. In this study, we designed/used a novel extracellular matrix, namely, a hybrid gel made of billions of injectable small thermally and pH-sensitive poly(N-isopropylacrylamide-co-acrylic acid) microgels whose swelling at the body pH and temperature physically jammed them and mesenchymal stem cells together, which enabled us to in situ apply an adjustable mechanical stress on those embedded stem cells. By treating the cell layer with the microgels, we found that an earlier incorporation of the microgels significantly increases the alkaline phosphatase activity, while a later addition of the microgels after the primary calcium deposition enhances the extracellular matrix mineralization in the mesenchymal stem cells cultures accompanied by up-regulation of osteogenic marker genes expression, presumably due to the calcium fixation by the carboxyl groups inside the microgels and the physical contact between the microgels and mesenchymal stem cells layers. These microgels provide an extracellular matrix microenvironment to affect the fate and biological behavior of mesenchymal stem cells, facilitating their potential applications in regenerative therapies.


Assuntos
Materiais Biocompatíveis/química , Células-Tronco Mesenquimais/citologia , Osteogênese , Acrilamidas/química , Fosfatase Alcalina/metabolismo , Animais , Fenômenos Biomecânicos , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Matriz Extracelular/química , Hidrogéis , Concentração de Íons de Hidrogênio , Teste de Materiais , Células-Tronco Mesenquimais/metabolismo , Camundongos , Osteopontina/genética , Osteopontina/metabolismo , Polímeros/química , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Temperatura
10.
Chem Commun (Camb) ; 51(48): 9785-8, 2015 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-25986474

RESUMO

This communication describes the fabrication of Pt/CeO2 nanotube@SiO2 core-shell catalysts applied to highly efficient water-gas shift reaction, where the initial CO conversion is 30.2% at 250 °C. Pt/CeO2 nanotube@SiO2 core-shell catalysts show outstanding thermal stability, even after accelerated aging under reaction conditions at 450 °C for 6 h, and the morphology is also unchanged after thermal treatment at 800 °C.


Assuntos
Cério/química , Nanotubos/química , Platina/química , Dióxido de Silício/química , Catálise , Temperatura Alta , Microscopia Eletrônica de Transmissão , Nanotubos/ultraestrutura , Povidona/química
11.
J Orthop Res ; 26(4): 539-46, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17960653

RESUMO

We have previously demonstrated that injections of the thrombin-related peptide, TP508, into the lengthening gap have significantly enhanced bone consolidation in a rabbit model of distraction osteogenesis. This study was to further test the effect of a single TP508 injection in slow release preparation on bone formation during distraction osteogenesis. Rabbits had left tibiae lengthened unilateral lengthener at rate of 1.4 mm/day for 6 days. TP508 was injected into as the following: Group 1, TP508 in saline; Group 2, in PPF/PLGA [poly(propylene fumarate)/poly(D,L-lactic-co-glycolic acid)] microparticles; and Group 3, dextran gel only. All the animals were killed 2 weeks after lengthening. On radiographies, more bone was formed in the two TP508-treated groups at first and secnd week postlengthening than that of the control Group 3. Microcomputed tomography (microCT) at 2 weeks indicated that the most advanced bone formation and remodeling was seen in Group 2. The mean volumetric BMD of the regenerates was significantly higher in the TP508 treated groups compared to the control group (p < 0.05). Histological evaluations supported the radiographic and the microCT results. In conclusion, we have demonstrated that a single injection of small amount of TP508 (300 microg) at the end of lengthening phases has significantly enhanced bone consolidation process in a rabbit model of distraction osteogenesis. The delivery of TP508 in PPF/PLGA microparticles appears to lead to a better quality bone formation over the saline delivery, further examinations are needed to confirm if PPF/PLGA microparticles may be desirable drug delivery form in augmenting bone formation.


Assuntos
Osteogênese por Distração , Osteogênese/efeitos dos fármacos , Fragmentos de Peptídeos/administração & dosagem , Tíbia/efeitos dos fármacos , Animais , Materiais Biocompatíveis , Portadores de Fármacos , Fumaratos , Injeções Intralesionais , Ácido Láctico , Masculino , Microesferas , Ácido Poliglicólico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Polímeros , Polipropilenos , Coelhos , Trombina , Tíbia/diagnóstico por imagem , Tíbia/patologia , Tomografia Computadorizada por Raios X
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