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Integrins are heterodimers composed of two subunits, α(120-185kD) and ß (90-110kD), which mediate the connection between cells and their external environment, such as extracellular matrix (ECM), and play an important role in the regulation of cell shape, proliferation and migration. Herein, we identified a potent anti-tumor migration peptide Accutin from crude venom of Agkistrodon acutus using an A549 3D tumor sphere model, and simulation tools and RNA sequencing were performed to reveal the mechanism of Accutin. Accutin is a disintegrin and docking, molecular dynamics simulations and ITC assay indicate that the RGD motif in the Accutin sequence can stably bind to integrins α5ß1. 9.22 nM Accutin can significantly inhibit the migration and invasion of lung cancer cell lines. Transcriptome analysis indicated that many genes are involved in tumor cell adhesion-related biological processes. Several pathways, like the "mTOR signaling pathway", "TGF-ß signaling pathway", and "Focal adhesion" were enriched. Interestingly, pathways involved in "N-Glycan biosynthesis" etc. were significantly inhibited. These transcriptomics data suggested that the molecular basis of Accutin-mediated inhibition of cancer cell migration may be by inhibiting N-glycosylation of integrin, then inhibiting signaling pathways such as PI3K/AKT/mTOR and TGFß/smad. Western blotting analysis further confirmed that Accutin could suppress migration via down-regulating the phosphorylation of FAK and AKT and inhibiting EMT (epithelial-mesenchymal transition). Taken together, as a disintegrin with high efficiency, Accutin may be a potential precursor of a therapeutic agent for the treatment of lung cancer migration.
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Movimento Celular , Transição Epitelial-Mesenquimal , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Humanos , Movimento Celular/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Células A549 , Quinase 1 de Adesão Focal/metabolismo , Desintegrinas/farmacologia , Desintegrinas/química , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológicoRESUMO
Anti-cancer peptides (ACPs) represent a promising potential for cancer treatment, although their mechanisms need to be further elucidated to improve their application in cancer therapy. Lycosin-I, a linear amphipathic peptide isolated from the venom of Lycosa singorensis, shows significant anticancer potential. Herein, it is found that Lycosin-I, which can self-assemble into a nanosphere structure, has a multimodal mechanism of action involving lipid binding for the selective and effective treatment of leukemia. Mechanistically, Lycosin-I selectively binds to the K562 cell membrane, likely due to its preferential interaction with negatively charged phosphatidylserine, and rapidly triggers membrane lysis, particularly at high concentrations. In addition, Lycosin-I induces apoptosis, cell cycle arrest in the G1 phase and ferroptosis in K562 cells by suppressing the PI3K-AKT-mTOR signaling pathway and activating cell autophagy at low concentrations. Furthermore, intraperitoneal injection of Lycosin-I inhibits tumor growth of K562 cells in a nude mouse xenograft model without causing side effects. Collectively, the multimodal effect of Lycosin-I can provide new insights into the mechanism of ACPs, and Lycosin-I, which is characterized by high potency and specificity, can be a promising lead for the development of anti-leukemia drugs.
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Leucemia , Camundongos Nus , Animais , Camundongos , Humanos , Leucemia/tratamento farmacológico , Células K562 , Apoptose/efeitos dos fármacos , Venenos de Aranha/farmacologia , Venenos de Aranha/química , Modelos Animais de Doenças , Antineoplásicos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Linhagem Celular Tumoral , Peptídeos/farmacologia , Peptídeos Catiônicos AntimicrobianosRESUMO
Vaccines against influenza and many other infectious diseases require multiple boosters in addition to the primary dose to improve efficacy, but this approach is not ideal for compliance. The multiple doses could potentially be replaced by sustained or pulsatile release of antigens encapsulated in degradable microparticles (MPs). The efficacy of a vaccine is improved by adding an adjuvant, which can be co-delivered from the particles to enhance immunogenicity. Here, we developed degradable poly-lactic-co-glycolic acid (PLGA) (7-17 kDa) MPs capable of sustained release of ultraviolet killed influenza virus (A/PR/8/34) (kPR8) vaccine and the natural killer T (NKT) cell agonist alpha-galactosylceramide (α-GalCer) and tested their effectiveness at providing long-term protection against influenza virus infection in mice. Multiple formulations were developed for encapsulating the virus and adjuvant separately, and in combination. The MPs exhibited sustained release of both the virus and the adjuvant lasting more than a month. Co-encapsulation significantly increased the encapsulation efficiency (EE) of the vaccine but reduced the release duration. On the other hand, co-encapsulation led to a reduction in EE for the α-GalCer and a change in release profile to a higher initial burst followed by a linear release compared to a low initial burst and slower linear release. The α-GalCer also had considerably longer release duration compared to the vaccine. Mice injected with particle formulations co-encapsulating kPR8 and α-GalCer were protected from a lethal influenza virus infection 30 weeks after vaccination. This study demonstrates that PLGA MP based vaccines are promising for providing effective vaccination and possibly for replacing multiple doses with a single injection.
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Preparações de Ação Retardada , Galactosilceramidas , Vacinas contra Influenza , Células T Matadoras Naturais , Infecções por Orthomyxoviridae , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Animais , Galactosilceramidas/administração & dosagem , Galactosilceramidas/imunologia , Galactosilceramidas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Camundongos , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/química , Células T Matadoras Naturais/imunologia , Células T Matadoras Naturais/efeitos dos fármacos , Infecções por Orthomyxoviridae/prevenção & controle , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/virologia , Feminino , Camundongos Endogâmicos BALB C , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/farmacologia , Camundongos Endogâmicos C57BL , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/administração & dosagemRESUMO
Influenza vaccines administered as intramuscularly injected inactivated viruses or intranasally administered live-attenuated viruses usually provide short-term protection against influenza infections. Biodegradable particles that provide sustained release of the antigen has been studied as an approach to extend vaccine protection. Here, we investigate sustained release of ultraviolet killed influenza A virus (A/PR/8/34(H1N1)) (kPR8) loaded into poly(D,L-lactic-co-glycolic acid) (PLGA) microparticles. Particles were prepared using the double emulsion method, and polymer molecular weight (MW), polymer hydrophobicity, polymer concentration in the organic phase, and the amount of killed virus were varied to obtain a range of particles. Formulations included PLGA 50:50 (2-6, 7-17 kDa), PLGA 75:25 (4-15 kDa), and 50/50 PLGA 75:25 (4-15 kDa)/PCL (14 kDa). Additionally, NaOH was co-encapsulated in some cases to enhance particle degradation. The structure of the particles was explored by size measurements and electron microscopy. The kPR8 release profiles were measured using hemagglutinin ELISA. The concentration of the polymer (PLGA) in the organic phase and polymer MW significantly influenced virus loading, while polymer MW and co-encapsulation of NaOH modulated the release profiles. Mice receiving a single intramuscular injection of NaOH microparticle-encapsulated kPR8 were partially protected against a lethal influenza challenge 32 weeks post immunization. Microparticle (MP) vaccination induced a gradual increase in PR8-specific IgGs dominated by IgG1 in contrast to the rapid IgG2a-biased response elicited by soluble kPR8 immunization. Our results indicate that vaccine-NaOH co-loaded PLGA particles show potential as a single dose vaccination strategy for extended protection against influenza virus infection.
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Preparações de Ação Retardada , Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza , Ácido Láctico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Vírus da Influenza A Subtipo H1N1/imunologia , Animais , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Camundongos , Ácido Láctico/química , Vacinação/métodos , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Ácido Poliglicólico/química , Feminino , Infecções por Orthomyxoviridae/prevenção & controle , Infecções por Orthomyxoviridae/virologia , Infecções por Orthomyxoviridae/imunologia , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/imunologia , Microesferas , Injeções IntramuscularesRESUMO
In recent years, virtual reality (VR) technology has emerged as a powerful tool in the field of therapeutic landscapes. For hospitalized patients or individuals with limited mobility, VR provides highly personalized therapy by simulating authentic natural environments within a safe, convenient, and engaging setting. This study investigated the effectiveness of immersing patients in virtual natural environments for health recovery and compared the varying impacts of different types of landscapes on patients' recovery levels. The aim was to complement traditional medical approaches and enhance environmental design in the field of public health. Researchers systematically reviewed databases (January 2018 to August 2, 2023) to identify randomized controlled trials comparing the efficacy of virtual nature immersion with other treatments. The inclusion/exclusion criteria were established based on the population, intervention, comparison, outcomes, study design, and other aspects (expanded PICO) framework. The Cochrane tool was employed to assess the risk of bias. Meta-analysis was conducted by pooling the mean differences with a 95% confidence interval. Among 30 trials, a total of 2123 patients met the inclusion criteria, with 15 studies included in the meta-analysis. 30 trials met the criteria. Results show significant improvements in pain, anxiety, fear, and some physiological indicators with virtual nature-based treatments. On the other hand, natural scenes incorporating blue and green elements have been applied more extensively and have shown more significant effects. In comparison to conventional methods, this study strongly advocates that virtual reality environments are a crucial tool in bridging the gap between patients and nature, demonstrating their potential to reshape medical interventions and improve environmental design in the field of public health.
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Saúde Pública , Ensaios Clínicos Controlados Aleatórios como Assunto , Realidade Virtual , Humanos , Planejamento Ambiental , Terapia de Exposição à Realidade Virtual/métodosRESUMO
The MYB (v-Myb avivan myoblastsis virus oncogene homolog) transcription factor family is one of the largest families of plant transcription factors which plays a vital role in many aspects of plant growth and development. MYB-related is a subclass of the MYB family. Fifty-nine Arabidopsis thaliana MYB-related (AtMYB-related) genes have been identified. In order to understand the functions of these genes, in this review, the promoters of AtMYB-related genes were analyzed by means of bioinformatics, and the progress of research into the functions of these genes has been described. The main functions of these AtMYB-related genes are light response and circadian rhythm regulation, root hair and trichome development, telomere DNA binding, and hormone response. From an analysis of cis-acting elements, it was found that the promoters of these genes contained light-responsive elements and plant hormone response elements. Most genes contained elements related to drought, low temperature, and defense and stress responses. These analyses suggest that AtMYB-related genes may be involved in A. thaliana growth and development, and environmental adaptation through plant hormone pathways. However, the functions of many genes do not occur independently but instead interact with each other through different pathways. In the future, the study of the role of the gene in different pathways will be conducive to a comprehensive understanding of the function of the gene. Therefore, gene cloning and protein functional analyses can be subsequently used to understand the regulatory mechanisms of AtMYB-related genes in the interaction of multiple signal pathways. This review provides theoretical guidance for the follow-up study of plant MYB-related genes.
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Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Seguimentos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , OncogenesRESUMO
Wearable electronic sensors that can perform real-time, continuous, and high-fidelity monitoring of diverse biophysical signals from the human body are burgeoning and exhibit great potential to transform traditional clinical healthcare. However, such emerging devices often suffer from strict requirements of special precursor materials and sophisticated fabrication procedures. Here, we present a new paradigm of a self-powered, skin-attachable, and multifunctional sensing platform that can be fully created just at home with daily necessities. Its operating mechanism is based on mechanical/thermal regulation of the potential difference output of a primary electrochemical cell. This proposed sensing platform is totally self-powered and can be conformally attached to the skin for continuous monitoring of both mechanical and thermal stimulations. A wide spectrum of vital physiological signs of the human body, including body temperature, heart/pulse rate, respiratory rate, coughing, and body motions, can be continuously monitored and analyzed with this home-made sensing platform. This study demonstrates that the lab-conducted professional and expensive scientific research can also be accomplished at home, opening up new opportunities for home-centered healthcare in low-resource environments. Moreover, this work can serve as a handy and cost-efficient prototype for classroom education and clinical training purposes.
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Dispositivos Eletrônicos Vestíveis , Humanos , Eletrônica , Pele , Temperatura Corporal , Monitorização FisiológicaRESUMO
The article presents for the first time a pill-based ingestible electronics with CMOS integrated multiplexed fluorescence bio-molecular sensor arrays, bi-directional wireless communication and packaged optics in a FDA-approved capsule for in-vivo bio-molecular sensing. The silicon chip integrates both the sensor array, and the ultra-low-power (ULP) wireless system that allows offloading sensor computing to an external base station that can reconfigure the sensor measurement time, and its dynamic range, allowing optimized high sensitivity measurement under low power consumption. The integrated receiver achieves -59 dBm receiver sensitivity dissipating 121 µW of power. The integrated transmitter operates in a dual mode FSK/OOK delivering -15 dBm of power. The 15-pixel fluorescence sensor array follows an electronic-optic co-design methodology and integrates the nano-optical filters with integrated sub-wavelength metal layers that achieves high extinction ratio (39 dB), thereby eliminating the need for bulky external optical filters. The chip integrates photo-detection circuitry and on-chip 10-bit digitation, and achieves measured sensitivity of 1.6 attomoles of fluorescence labels on surface, and between 100 pM to 1 nM of target DNA detection limit per pixel. The complete package includes a CMOS fluorescent sensor chip with integrated filter, a prototyped UV LED and optical waveguide, functionalized bioslip, off-chip power management and Tx/Rx antenna that fits in a standard FDA approved capsule size 000.
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Eletrônica , Tecnologia sem Fio , Desenho de Equipamento , DNA , MetaisRESUMO
Recently, combining immunotherapy and chemotherapy has become a promising strategy to treat cancer. However, this therapeutic strategy still has its limitations because of the adverse effects caused by the simultaneous administration of multiple therapeutic agents. Using nanoparticles is an effective approach to successfully combine these therapies because they can reduce side effects, increase circulation time, and ensure the delivery of cytotoxic agents to tumor tissues. In this study, dual pH-sensitive and tumor microenvironment (TME)-active targeting micelles comprising poly(propyl methacrylate-co-glucosamine/histidine/doxorubicin) (P(PAA-co-GLU/HIS/DOX) and methoxy-poly(ethylene glycol)-block-poly(l-lysine) were prepared to encapsulate an immunomodulator, imiquimod (IMQ). Because these micelles can expose glucose targeting ligands at the TME and pH-dependently release IMQ and DOX, micelles effectively inhibit the growth of 4T1 cells selectively and highly accumulate in 4T1 cells as the pH decreased to 6.5. Moreover, in RAW 264.7 âcells, these micelles prevent cell death and induce M1 macrophage polarization. In 4T1 orthotopic tumor-bearing mice, micelles not only exhibited high tumor accumulation, effective tumor inhibition, and fewer adverse effects, but also dramatically increased the number of mature dendritic cells, activate cytotoxic T cells, and polarize M1-like macrophages in tumor tissues. Overall, these micelles exhibit precise pH responsiveness and ideal drug delivery capabilities for combined chemo- and immunotherapy; these results significantly contribute to the future development of nanomedicines in cancer therapy.
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A simple, selective, and quantitative platform for point-of-care diagnostic of COVID-19 is urgently needed as a complement in areas where resources are currently relatively scarce. To meet the needs of early diagnosis and intervention, a proof-of-concept demonstration of a universal personal glucose meter-based nucleic acid assay platform (PGM-NAAP) is presented, which converts to SARS-CoV-2 detection from glucose detection. By using magnetic bead separation together with the hand-held PGM for quantitative readout, PGM-NAAP achieves the 98 pM limit of detection for a sequence related to SARS-CoV-2. The ability to discriminate target nucleic acid from genomic DNA, the satisfactory spike recoveries of saliva and serum samples, as well as the good stability all together suggest the potential of the PGM-NAAP for the screening and diagnosis of suspected patients during the outbreaks of COVID-19 in resource-limited settings without sophisticated instruments. On the basis of these findings, PGM-NAAP can be expected to provide an accurate and convenient path for diagnosis of disease-associated nucleic acid.
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COVID-19 , Ácidos Nucleicos , COVID-19/diagnóstico , Glucose , Humanos , Técnicas de Amplificação de Ácido Nucleico , Sistemas Automatizados de Assistência Junto ao Leito , SARS-CoV-2/genéticaRESUMO
OBJECTIVE: This paper sets out to investigate the miR-205 and HMGB1 expressions in chronic periodontitis (PO) patients and their associations with the inflammatory factors. METHODS: From February 2016 to May 2018, 68 PO patients treated in our hospital were recruited for the study and placed in a patient group (PG), and 60 healthy volunteers were also recruited and placed in a healthy group (HG). Serum samples were collected from both groups for the identification of miR-205 using qPCR, as well as to determine the HMGB1 and inflammatory factor (IL-1ß, IL-6, TNF-α) expression levels using ELISA. The correlations of the miR-205 and HMGB1 expression levels with the periodontal clinical indicators and the inflammatory factors were analyzed using a correlation analysis. RESULTS: In comparison with the HG expression, the serum miR-205 expression was lower, and the HMGB1 was elevated in PG (P < 0.05). An ROC curve analysis showed that the areas under the curve (AUCs) of the serum miR-205 and HMGB1 expressions in diagnosing PO were 0.936 and 0.955 respectively. However, the serum miR-205 expression in PG increased while the HMGB1 expression decreased post treatment (P < 0.05). A correlation analysis revealed an inverse association between the serum miR-205 expression levels and the periodontal clinical indicators [bleeding index (BI), probing depth (PD), plaque index (PLI), and attachment loss (AL)], and the inflammatory factors [interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α)], but there was a positive association between the HMGB1 expression level and these parameters. CONCLUSIONS: miR-205 and HMGB1 are closely related to the progression of PO, and may be candidate biomarkers for the diagnosis and treatment of PO.
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In the treatment of cancers, small interfering ribonucleic acids (siRNAs) are delivered into cells to inhibit the oncogenic protein's expression; however, polyanions, hydrophilicity, and rapid degradations in blood, endosomal or secondary lysosomal degradation hamper clinal applications. In this study, we first synthesized and characterized two copolymers: methoxy poly(ethylene glycol)-b-poly(2-hydroxy methacrylate-ketal-pyridoxal) and methoxy poly(ethylene glycol)-b-poly(methacrylic acid-co-histidine). Afterwards, we assembled two polymers with the focal adhesion kinase (FAK) siRNA, forming polyplex-mixed micelles for the treatment of the human colon cancer cell line HCT116. In terms of the physiological condition, the cationic pyridoxal molecules that were conjugated on the copolymer with ketal bonds could electrostatically attract the siRNA. Additionally, the pyridoxal could form a hydrophobic core together with the hydrophobic deprotonated histidine molecules in the other copolymer and the hydrophilic polyethylene glycol (PEG) shell to protect the siRNA. In an acidic condition, the pyridoxal would be cleaved from the polymers due to the breakage of the ketal bonds and the histidine molecules can simultaneously be protonated, resulting in the endosome/lysosome escape effect. On the basis of our results, the two copolymers were successfully prepared and the pyridoxal derivatives were identified to be able to carry the siRNA and be cleavable by the copolymers in an acidic solution. Polyplex-mixed micelles were prepared, and the micellar structures were identified. The endosome escape behavior was observed using a confocal laser scanning microscopy (CLSM). The FAK expression was therefore reduced, and the cytotoxicity of siRNA toward human colon cancer cells was exhibited, rapidly in 24 h. This exceptional anticancer efficiency suggests the potential of the pH-sensitive polyplex-mixed micellar system in siRNA delivery.
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Urinary polycyclic aromatic hydrocarbon (PAH) metabolites, biomarkers of internal PAH exposure, are commonly used to explore the effects of PAH on human health. However, the correlation between environmental PAH exposure and the species or levels of urinary PAH metabolites remains unclear. We collected detailed information on PAH exposure sources, including cigarette smoking, cooking, traffic and diet habits via structured questionnaires, and determined 12 urinary monohydroxylated PAH metabolites (OH-PAHs) among 4092 participants from the Wuhan-Zhuhai cohort. Linear mixed models and generalized linear models were conducted to explore the associations of urinary metabolite levels with single or multiple PAH exposure sources. We also calculated the standardized regression coefficients to further compare the contributions of different sources to urinary OH-PAH levels. Our results showed that increasing levels of urinary 1-, 2-hydroxynaphthalene (1-, 2- OHNa) and 2-hydroxyfluorene (2-OHFlu) were significantly correlated with tobacco smoking (all Pâ¯<â¯0.01). The concentrations of 1-, 2- OHNa and 9-hydroxyfluorene (9-OHFlu) were positively correlated with dietary intake (all Pâ¯<â¯0.05). Individuals who spent a long time in traffic showed elevated levels of 9-OHFlu and 1-hydroxyphenanthrene (1-OHPh) compared with individuals who spent a short time in traffic (all Pâ¯<â¯0.05). Self-cooking was associated only with elevated 1-hydroxypyrene (1-OHP) levels. Moreover, good kitchen ventilation resulted in significantly decreased urinary low-molecular-weight OH-PAH levels. These findings suggested that cigarette smoking, self-cooking, high dietary PAH intake and a long time spent in traffic were associated with increased levels of specific urinary PAH metabolites, and good kitchen ventilation effectively reduced the exposure to low-molecular-weight PAHs in self-cooking participants.
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Exposição Ambiental/análise , Poluentes Ambientais/urina , Hidrocarbonetos Policíclicos Aromáticos/urina , Adulto , Biomarcadores/urina , China , Estudos de Coortes , Estudos Transversais , Exposição Ambiental/estatística & dados numéricos , Feminino , Fluorenos , Humanos , Estilo de Vida , Modelos Lineares , Pulmão/metabolismo , Masculino , Naftóis , FenantrenosRESUMO
To reduce the side effects of immune drugs and the sustainable release of immune drugs on local parts, we have designed an injectable thermal-sensitive hydrogel containing an imiquimod-loaded liposome system. In the extracellular environment of tumor tissues (pH 6.4), 50% of the drug was released from the carrier, which could be a result of the morphological changes of the liposomal microstructure in the acidic environment. According to the results in animals, the drug-containing liposomes combined with hydrogel can be effectively applied in breast cancer therapy to delay the growth of tumors as well as to dramatically reduce the death rate of mice.
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Health-related quality of life (HRQOL) was reported to reflect overall quality of life and individual perceptions related to health. Decreased lung function is associated with reduced ventilation and oxygen intake and reported to affect body functions. However, the effect of lung function reduction on HRQOL is still unclear. A total of 8398 retired workers from Dongfeng-Tongji Cohort Study were included in this cross section study. Lung function was measured using an electronic spirometer. HRQOL was evaluated through a questionnaire designed according to the WHOQOL-BREF. The mean of the HRQOL scores of its four domains (physical health, psychological state, social relationships and environment) is the total HRQOL score. A general linear model was used to analyse the association between lung function and HRQOL. In the continuous analysis by the general linear model, FVC was associated with the total HRQOL, physical health domain and social relationships domain scores. In the categorical analysis, there was a linear trend between FVC and the total HRQOL and physical health scores. We also found a similar relationship between FEV1 and HRQOL scores. Further analysis suggested that elevated lung function could improve the scores of pain and discomfort facet and independence facet of physical health domain. The lung function was significantly positively associated with HRQOL in middle-aged and older Chinese.
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Pulmão/fisiologia , Qualidade de Vida , Idoso , China , Estudos Transversais , Feminino , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Testes de Função RespiratóriaRESUMO
pH-sensitive polymerâ»liposomes can rapidly release their payloads. However, it is difficult to simultaneously achieve stability and pH-responsiveness in the polymerâ»liposomes. In this study, stable and pH-sensitive crosslinked polymerâ»liposomes were fabricated through electrostatic interactions. The pH-sensitive copolymer methoxy poly(ethylene glycol)-block-poly(methacrylic acid)-cholesterol (mPEG-b-P(MAAc)-chol) and crosslinking reagent poly(ethylene glycol) with end-capped with lysine (PEG-Lys2) were synthesized and characterized. At physiological conditions, the pH-sensitive copolymers were anionic and interacted electrostatically with the cationic crosslinker PEG-Lys2, forming the electrostatically-crosslinked polymerâ»liposomes and stabilizing the liposomal structure. At pH 5.0, the carboxylic groups in mPEG-b-P(MAAc)-chol were neutralized, and the liposomal structure was destroyed. The particle size of the crosslinked polymerâ»liposomes was approximately 140 nm and the polymerâ»liposomes were loaded with the anticancer drug doxorubicin. At pH 7.4, the crosslinked polymerâ»liposomes exhibited good stability with steady particle size and low drug leakage, even in the presence of fetal bovine serum. At pH 5.0, the architecture of the crosslinked polymerâ»liposomes was damaged following rapid drug release, as observed by using transmission electron microscopy and their apparent size variation. The crosslinked polymerâ»liposomes were pH-sensitive within the endosome and in the human breast cancer cells MDA-MB-231, as determined by using confocal laser scanning microscopy. The intracellular drug release profiles indicated cytotoxicity in cancer cells. These results indicated that the highly-stable and pH-sensitive electrostatically-crosslinked polymerâ»liposomes offered a potent drug-delivery system for use in anticancer therapies.
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Antineoplásicos/química , Lipossomos/química , Polímeros/química , Linhagem Celular Tumoral , Doxorrubicina/química , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Humanos , Concentração de Íons de Hidrogênio , Microscopia Eletrônica de Transmissão , Polietilenoglicóis/químicaRESUMO
Multifunctional polymer nanoparticles have been developed for cancer treatment because they could be easily designed to target cancer cells and to enhance therapeutic efficacy according to cancer hallmarks. In this study, we synthesized a pH-sensitive polymer, poly(methacrylic acid-co-histidine/doxorubicin/biotin) (HBD) in which doxorubicin (DOX) was conjugated by a hydrazone bond to encapsulate an immunotherapy drug, imiquimod (IMQ), to form dual cancer-targeting and dual drug-loaded nanoparticles. At low pH, polymeric nanoparticles could disrupt and simultaneously release DOX and IMQ. Our experimental results show that the nanoparticles exhibited pH-dependent drug release behavior and had an ability to target cancer cells via biotin and protonated histidine.