ABSTRACT
Abstract The aim of the present study is to assess the effects of selenium nanoparticles on the growth, hematology and nutrients digestibility of Labeorohita fingerlings. Fingerlings were fed with seven isocaloric sunflower meal-based diet supplemented with different concentrations of nanoparticles naming T1 to T7 (0, 0.5, 1, 1.5, 2, 2.5, and 3 mg/kg), with 5% wet body weight while chromic oxide was used as an indigestible marker. After experimentation for 90 days T3 treated group (1mg/kg -1Se-nano level) showed the best result in hematological parameters (WBC's 7.97 ×103mm-3, RBC's 2.98 ×106 mm-3 and Platelet count 67), nutrient digestibility (crude protein: 74%, ether extract: 76%, gross energy: 70%) and growth performance (weight gain 13.24 g, weight gain% 198, feed conversion ratio 1.5, survival rate 100%) as compared to the other treatment groups. Specific growth rates were found significantly higher in T5 than in other groups. The present study indicated positive effect of 1 mg/kg Se-nanoparticles on growth advancement, hematological parameters, and nutrients digestibility of L. rohita fingerlings.
Resumo O objetivo do presente estudo é avaliar os efeitos das nanopartículas de selênio no crescimento, hematologia e digestibilidade dos nutrientes de alevinos de Labeo rohita. Os alevinos foram alimentados com sete dietas isocalóricas à base de farinha de girassol suplementada com diferentes concentrações de nanopartículas, nomeando T1 a T7 (0, 0,5, 1, 1,5, 2, 2,5 e 3 mg / kg), com 5% do peso corporal úmido enquanto o óxido crômico foi usado como um marcador indigesto. Após a experimentação por 90 dias, o grupo tratado com T3 (nível 1mg / kg -1Se-nano) mostrou o melhor resultado em parâmetros hematológicos (WBC's 7,97 × 103mm-3, RBC's 2,98 × 106mm-3 e contagem de plaquetas 67), digestibilidade dos nutrientes (proteína bruta: 74%, extrato de éter: 76%, energia bruta: 70%) e desempenho de crescimento (ganho de peso 13,24 g, ganho de peso % 198, taxa de conversão alimentar 1,5, taxa de sobrevivência 100%) em comparação com os outros grupos de tratamento. As taxas de crescimento específicas foram encontradas significativamente mais altas em T5 do que em outros grupos. O presente estudo indicou efeito positivo de 1 mg / kg de nanopartículas de Se no avanço do crescimento, parâmetros hematológicos e digestibilidade de nutrientes de alevinos de L. rohita.
Subject(s)
Animals , Nanoparticles , Helianthus , Nutrients , Dietary Supplements , Diet , Animal Feed/analysis , Animal Nutritional Physiological PhenomenaABSTRACT
Abstract The aim of the present study is to assess the effects of selenium nanoparticles on the growth, hematology and nutrients digestibility of Labeorohita fingerlings. Fingerlings were fed with seven isocaloric sunflower meal-based diet supplemented with different concentrations of nanoparticles naming T1 to T7 (0, 0.5, 1, 1.5, 2, 2.5, and 3 mg/kg), with 5% wet body weight while chromic oxide was used as an indigestible marker. After experimentation for 90 days T3 treated group (1mg/kg -1Se-nano level) showed the best result in hematological parameters (WBCs 7.97 ×103mm-3, RBCs 2.98 ×106 mm-3 and Platelet count 67), nutrient digestibility (crude protein: 74%, ether extract: 76%, gross energy: 70%) and growth performance (weight gain 13.24 g, weight gain% 198, feed conversion ratio 1.5, survival rate 100%) as compared to the other treatment groups. Specific growth rates were found significantly higher in T5 than in other groups. The present study indicated positive effect of 1 mg/kg Se-nanoparticles on growth advancement, hematological parameters, and nutrients digestibility of L. rohita fingerlings.
Resumo O objetivo do presente estudo é avaliar os efeitos das nanopartículas de selênio no crescimento, hematologia e digestibilidade dos nutrientes de alevinos de Labeo rohita. Os alevinos foram alimentados com sete dietas isocalóricas à base de farinha de girassol suplementada com diferentes concentrações de nanopartículas, nomeando T1 a T7 (0, 0,5, 1, 1,5, 2, 2,5 e 3 mg / kg), com 5% do peso corporal úmido enquanto o óxido crômico foi usado como um marcador indigesto. Após a experimentação por 90 dias, o grupo tratado com T3 (nível 1mg / kg -1Se-nano) mostrou o melhor resultado em parâmetros hematológicos (WBCs 7,97 × 103mm-3, RBCs 2,98 × 106mm-3 e contagem de plaquetas 67), digestibilidade dos nutrientes (proteína bruta: 74%, extrato de éter: 76%, energia bruta: 70%) e desempenho de crescimento (ganho de peso 13,24 g, ganho de peso % 198, taxa de conversão alimentar 1,5, taxa de sobrevivência 100%) em comparação com os outros grupos de tratamento. As taxas de crescimento específicas foram encontradas significativamente mais altas em T5 do que em outros grupos. O presente estudo indicou efeito positivo de 1 mg / kg de nanopartículas de Se no avanço do crescimento, parâmetros hematológicos e digestibilidade de nutrientes de alevinos de L. rohita.
ABSTRACT
Abstract The objective of this work was to evaluate the mechanical performance of Z350 resin composite modified with Bombyx mori cocoons silk nanoparticles for dental applications. Four experimental groups were analyzed G0% = Filtek Z350 resin composite (control); G1% = Filtek Z350 with 1% of silk nanoparticles; G3% = Filtek Z350 with 3% of silk nanoparticles; G5% = Filtek Z350 with 5% of silk nanoparticles. It was employed scanning electron microscopy, energy dispersive X-ray spectroscopy, X-ray diffraction, 3-point flexural strength test, Knoop hardness test, and surface roughness. From 3-point flexural strength tests the control group presented the best results G0% = 113.33 MPa (±23.73). The higher flexural modulus was shown by groups G3% = 29.150 GPa (±5.191) and G5% = 34.101 GPa (±7.940), which are statistically similar. The Knoop microhardness test has shown statistical difference only among the G3% group between the top 80.78 (± 3.00) and bottom 68.80 (±3.62) and no difference between the groups. The roughness test presented no statistical difference between the groups. The incorporation of silk nanoparticles reduced the flexural strength of Z350 resin composite. The surface roughness and microhardness tests showed no changes in any of the groups studied.
Resumo O objetivo deste trabalho foi avaliar o desempenho mecânico da resina composta Z350 modificada com nanopartículas de seda Bombyx mori cocoons para aplicações odontológicas. Quatro grupos experimentais foram analisados: G0%) Resina Z350 apenas (grupo controle); G1%) Reforço com 1% de nanopartículas de seda; G3%) Reforço com 3% de nanopartículas de seda; e G5%) Reforço com 5% de nanopartículas de seda. Foi empregado microscopia eletrônica de varredura, espectroscopia de energia dispersiva de raios X, difração de raios X, teste de resistência à flexão de 3 pontos, teste de dureza Knoop e rugosidade superficial. Nos testes de resistência à flexão de 3 pontos o grupo controle apresentou melhores resultados G0% = 0.113 GPa (±0.024). O maior módulo de flexão foi demonstrado pelos grupos G3% = 29.151GPa (±5.191) e G5% = 34.102 GPa (±7.94), que são estatisticamente semelhantes. O teste de microdureza Knoop mostrou diferença estatística apenas entre o grupo G3% entre os 80.78 superiores (± 3.00) e os 68.80 inferiores (±3.62). Não há diferença entre os grupos. O teste de rugosidade não apresentou diferença estatística entre os grupos. A incorporação de nanopartículas de seda reduziu a resistência à flexão da resina composta Z350. Os testes de rugosidade superficial e microdureza não apresentaram alterações em nenhum dos grupos estudados.
ABSTRACT
Size and surface modification are the two key factors affecting the effect of macrophages polarization induced by superparamagnetic iron oxide nanoparticles (SPIONs). The smaller the particle size, the better the polarization effect of SPIONs. Besides, the reasonable SPIONs surface modification method can also be used to enhance the polarization effect. In this study, SPIONs was prepared by solvothermal method and optimized by Box-Benhnken center combination design and response surface method. Furthermore, astragalus polysaccharide-superparamagnetic iron oxide nanocomplex (APS-SPIONs) was successfully constructed by EDC/NHS esterification method. The structure of APS-SPIONs was confirmed by dynamic light scatter and infrared spectrometer, and the contents of iron and polysaccharide were characterized by spectrophotometry. The effect of APS-SPIONs on inducing mouse macrophages RAW264.7 polarization was investigated by flow cytometry. The RAW264.7 macrophages-HepG2 human hepatoma cancer cells Transwell co-culture system was established to investigate APS-SPIONs improve anti-tumor function of macrophages in vitro, and the proliferation activity of APS-SPIONs on RAW264.7 detected by cell counting kit-8 (CCK-8) method. The results showed that the average particle size and zeta potential of APS-SPIONs were (82.93 ± 1.47) nm and (-24.00 ± 0.47) mV. Polysaccharide and Fe content were 8.69% and 7.04%, respectively. APS-SPIONs effectively induced the polarization of RAW264.7 into M1 type in vitro, improving the anti-tumor ability of macrophages in a co-culture system, without effecting the proliferation of macrophages. Our study provides a drug development strategy and preliminary research results to educate macrophages and reshape the tumor immune microenvironment to achieve tumor-killing effects.
ABSTRACT
Lung is susceptible to external disturbance, resulting in a variety of acute and chronic lung diseases. Functionalized nanoparticles as carriers can carry drugs through multiple biological barriers of lung into lung lesions, but there are some problems such as poor targeting and low therapeutic efficiency. As a drug carrier, membrane-coated biomimetic nanoparticles have the characteristics of immune system escape, active targeting, inflammatory chemotaxis and crossing physiological barriers due to the retention of the characteristics of the source cells. Therefore, it has been widely used in the treatment of lung diseases in recent years. In this review, the application of membrane-coated biomimetic nanoparticles in the treatment of lung diseases in the recent years was summarized and classified. Cell membrane sources include erythrocyte membrane, platelet membrane, macrophage membrane, neutrophil membrane, lung epithelial membrane, lung surfactant, endothelial membrane, cancer cell membrane, bacterial membrane, hybrid membrane and so on. The purpose of this review is to provide a new idea for treating lung diseases with membrane-coated biomimetic nanoparticles.
ABSTRACT
Polymer nanoparticles generally refer to hydrophobic polymers-based nanoparticles, which have been extensively studied in the nanomedicine field due to their good biocompatibility, efficient long-circulation characteristics, and superior metabolic discharge patterns over other nanoparticles. Existing studies have proved that polymer nanoparticles possess unique advantages in the diagnosis and treatment of cardiovascular diseases, and have been transformed from basic researches to clinical applications, especially in the diagnosis and treatment of atherosclerosis (AS). However, the inflammatory reaction induced by polymer nanoparticles would induce the formation of foam cells and autophagy of macrophages. In addition, the variations in the mechanical microenvironment of cardiovascular diseases may cause the enrichment of polymer nanoparticles. These could possibly promote the occurrence and development of AS. Herein, this review summarized the recent application of polymer nanoparticles in the diagnosis and treatment of AS, as well as the relationship between polymer nanoparticles and AS and the associated mechanism, with the aim to facilitate the development of novel nanodrugs for the treatment of AS.
Subject(s)
Humans , Polymers/chemistry , Cardiovascular Diseases , Nanoparticles/chemistry , Drug Delivery Systems , Atherosclerosis/pathologyABSTRACT
Deficiency of natural killer (NK) cells shows a significant impact on tumor progression and failure of immunotherapy. It is highly desirable to boost NK cell immunity by upregulating active receptors and relieving the immunosuppressive tumor microenvironment. Unfortunately, mobilization of NK cells is hampered by poor accumulation and short retention of drugs in tumors, thus declining antitumor efficiency. Herein, we develop an acid-switchable nanoparticle with self-adaptive aggregation property for co-delivering galunisertib and interleukin 15 (IL-15). The nanoparticles induce morphology switch by a decomposition-metal coordination cascade reaction, which provides a new methodology to trigger aggregation. It shows self-adaptive size-enlargement upon acidity, thus improving drug retention in tumor to over 120 h. The diameter of agglomerates is increased and drug release is effectively promoted following reduced pH values. The nanoparticles activate both NK cell and CD8+ T cell immunity in vivo. It significantly suppresses CT26 tumor in immune-deficient BALB/c mice, and the efficiency is further improved in immunocompetent mice, indicating that the nanoparticles can not only boost innate NK cell immunity but also adaptive T cell immunity. The approach reported here provides an innovative strategy to improve drug retention in tumors, which will enhance cancer immunotherapy by boosting NK cells.
ABSTRACT
Given the complexity of biological samples and the trace nature of target materials in forensic trace analysis, a simple and effective method is needed to obtain sufficient target materials from complex substrates. Magnetic nanoparticles (MNPs) have shown a wide range of application value in many research fields, such as biomedicine, drug delivery and separation, due to their unique superparamagnetic properties, stable physical and chemical properties, biocompatibility, small size, high specific surface area and other characteristics. To apply MNPs in the pretreatment of forensic materials, maximize the extraction rate of the target materials, and minimize interference factors to meet the requirements of trace analysis of the target materials, this paper reviews the application of MNPs in the fields of forensic toxicological analysis, environmental forensic science, trace evidence analysis and criminal investigation in recent years, and provides research ideas for the application of MNPs in forensic trace analysis.
Subject(s)
Magnetite Nanoparticles/chemistry , Forensic Medicine , Forensic Sciences , Forensic ToxicologyABSTRACT
Plant diseases and insect pests threaten the safety of crop production greatly. Traditional methods for pest management are challenged by the problems such as environmental pollution, off-target effects, and resistance of pathogens and insects. New biotechnology-based strategies for pest control are expected to be developed. RNA interference (RNAi) is an endogenous process of gene regulation, which has been widely used to study the gene functions in various organisms. In recent years, RNAi-based pest management has received increasing attention. The effective delivery of the exogenous interference RNA into the targets is a key step in RNAi-mediated plant diseases and pest control. Considerable advances were made on the mechanism of RNAi, and various RNA delivery systems were developed for efficient pest control. Here we review the latest advances on mechanisms and influencing factors of RNA delivery, summarize the strategies of exogenous RNA delivery in RNAi-mediated pest control, and highlight the advantages of nanoparticle complexes in dsRNA delivery.
Subject(s)
Animals , RNA Interference , Pest Control , Insecta/genetics , RNA, Double-Stranded , Gene Expression RegulationABSTRACT
Background Silica nanoparticles (SiNPs) enter the human body through respiratory tract, digestive tract, and skin, causing body damage. Lung is one of the main damaged organs. Objective To observe the expressions of complement activated fragment C3a and its receptor C3aR in the lungs of mice exposed to SiNPs through respiratory tract, and to explore the involvement of C3a/C3aR in lung injury induced by SiNPs exposure. Methods The ultrastructure of SiNPs (particle size 5-20 nm) was determined under a transmission electron microscope, and the hydrodynamic diameter and surface Zeta potential of SiNPs were determined using a nanoparticle size analyzer. A total of 88 SPF C57BL/6J mice were randomly divided into five groups: a blank control group without any treatment (14 mice), a vehicle control group treated with 50 μL stroke-physiological saline solution by intratracheal instillation (14 mice), and three SiNPs exposure groups (low-dose group, medium-dose group, and high-dose group with 20 mice in each group, who were given 50 μL SiNPs suspension of 7, 21, and 35 mg·kg−1 respectively and exposed once every 3 days for 5 times). The mice were anesthetized on day 1 (1-day model group) and day 15 (15-day model group) after exposure, then sacrificed after extraction of bronchoalveolar lavage fluid (BALF), and lung tissues were retained. The morphological changes of lung tissues were observed by HE staining, the expression level of C3a in BALF was detected by enzyme-linked immunosorbent assay, the deposition of C3a and C3aR in lung tissues were observed by immunohistochemistry, the protein expression level of C3aR was determined by Western blotting, and the localization and semi-quantitative detection of C3a and C3aR in lung tissues was observed by immunofluorescence. Results SiNPs agglomerated in stroke-physiological saline solution. The average hydrodynamic diameter was (185.60±7.39) nm and the absolute value of Zeta potential was (43.33±0.76) mV. The condition of mice in the 1-day model group and the 15-day model group was good, while 2 mice died in the medium-dose group of the 1-day model group due to misoperation. The autopsy results of the two mice showed congestion of the lung tissue, emphysema, and no imperfection of trachea integrity. No death was observed in other dose groups. The HE staining results showed pathological damage to the mouse lung, including alveolar wall thickening and inflammatory cell infiltration after SiNPs exposure. The pathological damage became more serious with the increase of dose. Regarding pathological changes, the 15-day model group was slightly relieved compared with the 1-day model group, but there were still pathological changes. The enzyme-linked immunosorbent assay results showed that there was no difference in the expression level of C3a between the blank control group and the vehicle control group (P＞0.05), the expression levels of C3a in the medium-dose group and the high-dose group were significantly higher than that in the vehicle control group (P<0.05). The immunohistochemistry results showed that C3a deposition was consistent with the enzyme-linked immunosorbent assay results. The Western blotting and the immunohistochemistry results showed that C3aR expression was low in the blank control group and the vehicle control group, while the expression in each dose group tended to increase with the increase of dose. The immunofluorescence results showed that the fluorescence signals of C3a and C3aR were weak in the blank control group and the vehicle control group in the 1-day model group and the 15-day model group, while the fluorescence signals in the lung tissues of mice in the SiNPs exposure groups tended to increase with the increase of dose. Conclusion The increased expressions of C3a and C3aR in complement activation may be related to lung injury induced by intratracheal instillation of SiNPs, suggesting that C3a/C3aR may be involved in lung injury induced by SiNPs exposure.
ABSTRACT
Abstract Vascular endothelial growth factor (VEGF) is an essential angiogenic factor in breast cancer development and metastasis. Small interfering RNAs (siRNAs) can specifically silence genes via the RNA interference pathway, therefore were investigated as cancer therapeutics. In this study, we investigated the effects of siRNAs longer than 30 base pairs (bp) loaded into chitosan nanoparticles in triple-negative breast cancer cells, compared with conventional siRNAs. 35 bp long synthetic siRNAs inhibited VEGF gene expression by 51.2% and increased apoptosis level by 1.75-fold in MDA-MB-231 cell lines. Furthermore, blank and siRNA-loaded chitosan nanoparticles induced expression of IFN-γ in breast cancer cells. These results suggest that long synthetic siRNAs can be as effective as conventional siRNAs, when introduced into cells with chitosan nanoparticles
Subject(s)
RNA, Small Interfering/pharmacology , Vascular Endothelial Growth Factor A/analysis , Chitosan/adverse effects , Nanoparticles/classification , Triple Negative Breast Neoplasms/pathology , Neoplasm Metastasis/diagnosisABSTRACT
With the rapid development of nanotechnology, the research and development of nanomedicines have become one of the development directions of drug innovation. Nanomedicines have special physical and chemical properties, such as nanoscale effects and nanostructure effects, so they have special biological properties, which may change the pharmacokinetic profiles such as absorption and tissue distribution of drug molecules, and thus affect their safety and effectiveness. There are many special concerns on the non-clinical safety evaluation of nanomedicines at the basis of ordinary drug because of the particularity of nanomedicines. On August 25, 2021, China issued Guidance on Non-clinical Safety Evaluation for Nanomedicines(interim). This article interprets comprehensively the guidance, focuses on the key points of non-clinical safety evaluation for nanomedicines, and expounds combined with some cases, aiming to provide reference for drug researchers.
ABSTRACT
As an edible eukaryotic microorganism, Saccharomyces cerevisiae has the characteristics of high safety, rapid proliferation, low cost, easy transformation, etc. It has been widely used to produce vaccines, antibodies, insulin, etc. Up to now, yeast components, such as cell wall and yeast microcapsules, have been widely used in the treatment of tumors, inflammatory virus infection, post-traumatic osteoarthritis and other diseases. Among them, the components of yeast cell membrane are relatively simple and stable, which are easy to be extracted on a large scale. Therefore, yeast cell membrane material was used to construct yeast membrane vesicle nanosystem, and its biomedical application was preliminarily explored. In this study, Saccharomyces cerevisiae membrane vesicle (SMV) was prepared by co-extrusion method, and the particle size and surface potential of SMV, drug loading and release characteristics, stability, cell safety, and in vitro therapeutic effect were investigated. The results showed that the average particle size of SMV was 185.1 nm. Curcumin and silica nanoparticles were effectively encapsulated by co-incubation and ultrasonic methods, and the characteristics of cell membrane proteins were maintained. Moreover, SMV had good stability and biocompatibility. In addition, SMV could be effectively uptaken by macrophages RAW 264.7, and curcumin loaded SMV could effectively eliminate reactive oxygen species (ROS). In conclusion, the yeast plasma membrane vesicles prepared in this study could effectively deliver curcumin drugs and encapsulate nanoparticles, and could be effectively absorbed by macrophages and effectively eliminate ROS, providing new ideas and new methods for biomedical applications of yeast membrane materials.
ABSTRACT
Oral mucosal drug delivery has the advantages of rapid drug absorption, no first-pass effect and good patient compliance. However, factors such as low drug dissolution, saliva carrying the drug into the gastrointestinal tract and the existence of physiological barriers in the mucosa may affect the mucosal permeation and bioavailability of the drug. Nanotechnology applied to drug oral mucosa delivery can overcome the above disadvantages and obtain efficient absorption effect. This paper describes the physiological structure of oral mucosa and the factors affecting the absorption of drugs in oral mucosa, reviews the application of nanotechnology such as liposomes, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, polymer nanoparticles, polymer micelles and nanohybrid suspensions in oral mucosal drug delivery and the mechanism of promoting drug absorption, summarizes the main problems of current research, and gives an outlook on the application of nano oral mucosal drug delivery system. The main problems of current research are summarized, and the prospects for the application of nano oral mucosal drug delivery systems are discussed.
ABSTRACT
Small interfering RNA (siRNA) is the initiator of RNA interference and inhibits gene expression by targeted degradation of specific messenger RNA. siRNA-mediated gene regulation has high efficiency and specificity and exhibits great significance in the treatment of diseases. However, the naked or unmodified siRNA has poor stability, easy to degrade by nuclease, short half-life, and low intracellular delivery. As an emerging non-viral nucleic acid delivery system, ionizable lipid nanoparticles play an important role in improving the druggability of siRNA. At present, one siRNA drug based on ionizable lipid nanoparticles has been approved for the treatment of rare disease. This review introduces the research progress in ionizable lipid nanoparticles for siRNA delivery, focusing on the effect of each component of lipid nanoparticles on the efficiency of siRNA-mediated gene silencing, which provides new references for the studies on ionizable lipid nanocarriers for siRNA delivery.
ABSTRACT
To investigate the crucial role of particle size in the biological effects of nanoparticles, a series of mesoporous silica nanoparticles (MSNs) were prepared with particle size gradients (50, 100, 150, 200 nm) with the traditional Stober method and adjusting the type and ratio of the silica source. The correlation between toxicity and size-caused biological effects were then further examined both in vitro and in vivo. The results indicated that the prepared MSNs had a uniform size, good dispersal, and ordered mesoporous structure. Hemolytic toxicity was found to be independent of particle size. At the cellular level, MSNs with smaller particle sizes were more readily internalized by cells, which initiated to more intense oxidative stress, therefor inducing higher cytotoxicity, and apoptosis rate. In vivo studies demonstrated that MSNs primarily accumulated in the liver and kidneys of mice. Pharmacokinetic analysis revealed that larger MSNs were eliminated more efficiently by the urinary system than smaller MSNs. The mice's body weight monitoring, blood tests, and pathological sections of major organs indicated good biocompatibility for MSNs of different sizes. Animal welfare and the animal experimental protocols were strictly consistent with related ethics regulations of Zhejiang Chinese Medical University. Overall, this study prepared MSNs with a particle size gradient to investigate the correlation between toxicity and particle size using macrophages and endothelial cells. The study also examined the biosafety of MSNs with different particle sizes in vivo and in vitro, which could help to improve the safety design strategy of MSNs for drug delivery systems.
ABSTRACT
Objective To prepare and optimize the formulation of Albumin nanoparticles loading PROTAC molecule and observe the inhibition effect of nanoparticles on the proliferation and NAD+ metabolism of glioma cells. Methods Albumin nanoparticles loading NPT-B2 were prepared and characterized with a thermal driving method, and the prescription was optimized. An HPLC method was established to determine the content of NPT-B2. The proliferation inhibition of NPT-B2 and B2-BSA-NPs on U251 cells were investigated by the CCK8 method, and the degradation effects of NPT-B2 and B2-BSA-NPs on NAMPT in glioma cells were investigated by western blotting. Results The HPLC method was stable, with good linearity, precision, and recovery rate. The nanoparticles had a particle size of about 55.48 nm, a potential of about −12.9 mV, an encapsulation rate of about 94.74%, and a drug loading amount of about 8.61%. The IC50 of NPT-B2 on glioma cells was 61.16 nmol/L, which had a degradation effect on NAMPT. The IC50 of B2-BSA-NPs on glioma was 41.21 nmol/L, which had a very significant degradation effect on NAMPT. Conclusion Albumin nanoparticles loading PROTAC molecules were constructed. The prescription was optimized to improve the drug encapsulation rate, and the low water solubility of PROTAC molecule was improved, which had a significant inhibitory effect on the proliferation and NAD+ energy metabolism of glioma cells.
ABSTRACT
Drug resistance presents one of the major causes for the failure of cancer chemotherapy. Cancer stem-like cells (CSCs), a population of self-renewal cells with high tumorigenicity and innate chemoresistance, can survive conventional chemotherapy and generate increased resistance. Here, we develop a lipid-polymer hybrid nanoparticle for co-delivery and cell-distinct release of the differentiation-inducing agent, all-trans retinoic acid and the chemotherapeutic drug, doxorubicin to overcome the CSC-associated chemoresistance. The hybrid nanoparticles achieve differential release of the combined drugs in the CSCs and bulk tumor cells by responding to their specific intracellular signal variation. In the hypoxic CSCs, ATRA is released to induce differentiation of the CSCs, and in the differentiating CSCs with decreased chemoresistance, DOX is released upon elevation of reactive oxygen species to cause subsequent cell death. In the bulk tumor cells, the drugs are released synchronously upon the hypoxic and oxidative conditions to exert potent anticancer effect. This cell-distinct drug release enhances the synergistic therapeutic efficacy of ATRA and DOX with different anticancer mechanism. We show that treatment with the hybrid nanoparticle efficiently inhibit the tumor growth and metastasis of the CSC-enriched triple negative breast cancer in the mouse models.
ABSTRACT
Fluorescence-guided surgery (FGS) with tumor-targeted imaging agents, particularly those using the near-infrared wavelength, has emerged as a real-time technique to highlight the tumor location and margins during a surgical procedure. For accurate visualization of prostate cancer (PCa) boundary and lymphatic metastasis, we developed a new approach involving an efficient self-quenched near-infrared fluorescence probe, Cy-KUE-OA, with dual PCa-membrane affinity. Cy-KUE-OA specifically targeted the prostate-specific membrane antigen (PSMA), anchored into the phospholipids of the cell membrane of PCa cells and consequently showed a strong Cy7-de-quenching effect. This dual-membrane-targeting probe allowed us to detect PSMA-expressing PCa cells both in vitro and in vivo and enabled clear visualization of the tumor boundary during fluorescence-guided laparoscopic surgery in PCa mouse models. Furthermore, the high PCa preference of Cy-KUE-OA was confirmed on surgically resected patient specimens of healthy tissues, PCa, and lymph node metastases. Taken together, our results serve as a bridge between preclinical and clinical research in FGS of PCa and lay a solid foundation for further clinical research.
ABSTRACT
Platinum-based chemotherapy resistance is a key factor of poor prognosis and recurrence in hepatocellular carcinoma (HCC). Herein, RNAseq analysis revealed that elevated tubulin folding cofactor E (TBCE) expression is associated with platinum-based chemotherapy resistance. High expression of TBCE contributes to worse prognoses and earlier recurrence among liver cancer patients. Mechanistically, TBCE silencing significantly affects cytoskeleton rearrangement, which in turn increases cisplatin-induced cycle arrest and apoptosis. To develop these findings into potential therapeutic drugs, endosomal pH-responsive nanoparticles (NPs) were developed to simultaneously encapsulate TBCE siRNA and cisplatin (DDP) to reverse this phenomena. NPs (siTBCE + DDP) concurrently silenced TBCE expression, increased cell sensitivity to platinum treatment, and subsequently resulted in superior anti-tumor effects both in vitro and in vivo in orthotopic and patient-derived xenograft (PDX) models. Taken together, NP-mediated delivery and the co-treatment of siTBCE + DDP proved to be effective in reversing chemotherapy resistance of DDP in multiple tumor models.