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1.
BMC Pediatr ; 24(1): 380, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38824506

RESUMEN

BACKGROUND: The survival rate of children with biliary atresia (BA) after liver transplantation (LT) is significantly improved, and their quality of life has attracted much attention.This study aimed to investigate the cognition and its influencing factors in children with BA after primary living donor LT (BA-pLDLT) during infancy. METHODS: Children with BA were recruited 6 months after pLDLT at Children's Hospital of Chongqing Medical University (2018-2022). Demographic and clinical data were collected from the health information system. Cognition was assessed using the Chinese version of the Griffiths Mental Development scale (GMDS-C). Multivariate linear regression were used to analyze the influencing factors of their cognitive function. RESULTS: In total, 57 children with BA-pLDLT, aged 5.00(3.90-9.30) months at transplantation and 25.00(14.00-60.80) months at evaluation were included. The general developmental quotient (89.02 ± 12.07) and motor, language, eye-hand coordination, performance, and practical reasoning quotients of these children were significantly lower than the normative mean values of GMDS-C(P < 0.05). Of the 57 children, 16 (28.07%) had borderline developmental delay (DQ between 70 and 84), 3 (5.26%) had developmental delay (DQ < 70), and 11(19.29%) had language delay. Reoperation for biliary or vascular complications after pLDLT was a risk factor for decreased general development quotient and motor quotient and lower ZW at assessment was associated with decline motor quotient. CONCLUSION: Children with BA-pLDLT have varying degrees of developmental delays in early life. Reoperation and nutritional deficiencies had adverse effects on cognitive development.


Asunto(s)
Atresia Biliar , Cognición , Trasplante de Hígado , Donadores Vivos , Humanos , Atresia Biliar/cirugía , Trasplante de Hígado/efectos adversos , Masculino , Femenino , Lactante , Preescolar , Discapacidades del Desarrollo/etiología
2.
Molecules ; 28(3)2023 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-36770907

RESUMEN

Cancer is a severe threat to human life. Recently, various therapeutic strategies, such as chemotherapy, photodynamic therapy, and combination therapy have been extensively applied in cancer treatment. However, the clinical benefits of these therapeutics still need improvement. In recent years, supramolecular chemistry based on host-guest interactions has attracted increasing attention in biomedical applications to address these issues. In this review, we present the properties of the major macrocyclic molecules and the stimulus-response strategies used for the controlled release of therapeutic agents. Finally, the applications of supramolecular-macrocycle-based nanomaterials in cancer therapy are reviewed, and the existing challenges and prospects are discussed.


Asunto(s)
Nanoestructuras , Neoplasias , Fotoquimioterapia , Humanos , Sistemas de Liberación de Medicamentos , Nanoestructuras/uso terapéutico , Nanoestructuras/química , Neoplasias/tratamiento farmacológico
3.
Small ; 17(31): e2100578, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34190401

RESUMEN

Drug delivery systems (DDS) are extensively studied to improve the solubility, stability, pharmacokinetic, and biodistribution of chemotherapeutics. However, the drug delivery efficiency of traditional DDS is often limited by the complicated biological barriers in vivo. Herein, a multistage adaptive nanoparticle (MAN) that simultaneously overcomes multiple biological barriers to achieve tumor-targeted drug delivery with high efficiency is presented. MAN has a core-shell structure, in which both the core and the shell are made of responsive polymers. This structure allows MAN to present different surface properties to adapt to its surrounding biological microenvironment, thereby achieving enhanced stability in blood circulation, improved tumor accumulation and cellular internalization in tumor tissues, and effective release of drug in cells. With these unique characteristics, the MAN loaded with docetaxel achieves effective tumor suppression with reduced systemic toxicity. Furthermore, MAN can load almost any hydrophobic drugs, providing a general strategy for the tumor-targeted delivery of hydrophobic drugs to overcome the multiple biological barriers and improve the efficacy of chemotherapy.


Asunto(s)
Antineoplásicos , Nanopartículas , Antineoplásicos/farmacología , Línea Celular Tumoral , Docetaxel/farmacología , Sistemas de Liberación de Medicamentos , Humanos , Distribución Tisular
4.
Nano Lett ; 20(6): 4454-4463, 2020 06 10.
Artículo en Inglés | MEDLINE | ID: mdl-32401534

RESUMEN

Inspired by heat shock proteins (HSPs), a self-assembly nanochaperone (nChap) is developed as a novel nanovaccine for boosting antitumor immune responses. Taking advantage of HSP-like microdomains and surface-decorated mannose, this nChap can efficiently capture antigens and ferry them into the dendritic cells (DCs). Subsequently, the nChap can blast lysosomes by transforming the structure and property of surface microdomains, thereby promoting antigen escape and enhancing their cross-presentation in cytoplasm. As a result, the nChap-based nanovaccine can elicit both CD4+ and CD8+ T cell-based immune responses and shows an excellent preventive effect on melanoma. Further combination of the nanovaccine with antiprogrammed death-1 (anti-PD-1) checkpoint blockade offers effective inhibition on the growth of already-established melanoma. Therefore, this nC ap-based nanovaccine provides a simple and robust strategy in mimicking HSPs to realize structure-assisted antigen capture, surface-receptor-mediated DC internalization, and both activation of humoral immunity and cellular immunity, promising for efficient cancer immunotherapy.


Asunto(s)
Vacunas contra el Cáncer , Proteínas de Choque Térmico , Inmunoterapia , Melanoma , Linfocitos T CD8-positivos/inmunología , Células Dendríticas/inmunología , Humanos , Inmunidad , Melanoma/tratamiento farmacológico
5.
Adv Funct Mater ; 30(48)2020 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-34737689

RESUMEN

Internalization of Staphylococcus aureus by macrophages can inactivate bacterial killing mechanisms, allowing intracellular residence and dissemination of infection. Concurrently, these staphylococci can evade antibiotics that are frequently unable to pass mammalian cell membranes. A binary, amphiphilic conjugate composed of triclosan and ciprofloxacin is synthesized that self-assemble through micelle formation into antimicrobial nanoparticles (ANPs). These novel ANPs are stabilized through encapsulation in macrophage membranes, providing membrane-encapsulated, antimicrobial-conjugated NPs (Me-ANPs) with similar protein activity, Toll-like receptor expression and negative surface charge as their precursor murine macrophage/human monocyte cell lines. The combination of Toll-like receptors and negative surface charge allows uptake of Me-ANPs by infected macrophages/monocytes through positively charged, lysozyme-rich membrane scars created during staphylococcal engulfment. Me-ANPs are not engulfed by more negatively charged sterile cells possessing less lysozyme at their surface. The Me-ANPs kill staphylococci internalized in macrophages in vitro. Me-ANPs likewise kill staphylococci more effectively than ANPs without membrane-encapsulation or clinically used ciprofloxacin in a mouse peritoneal infection model. Similarly, organ infections in mice created by dissemination of infected macrophages through circulation in the blood are better eradicated by Me-ANPs than by ciprofloxacin. These unique antimicrobial properties of macrophage-monocyte Me-ANPs provide a promising direction for human clinical application to combat persistent infections.

6.
Nano Lett ; 19(11): 7662-7672, 2019 11 13.
Artículo en Inglés | MEDLINE | ID: mdl-31593471

RESUMEN

Tumor heterogeneity has been one of the most important factors leading to the failure of conventional cancer therapies due to the accumulation of genetically distinct tumor-cell subpopulations during the tumor development process. Due to the diversity of genetic mutations during tumor growth, combining the use of multiple drugs has only achieved limited success in combating heterogeneous tumors. Herein, we report a novel antitumor strategy that effectively addresses tumor heterogeneity by using a CRISPR/Cas9-based nanoRNP carrying a combination of sgRNAs. Such nanoRNP is synthesized from Cas9 ribonucleoprotein, any combinations of required sgRNAs, and a rationally designed responsive polymer that endows nanoRNP with high circulating stability, enhanced tumor accumulation, and the efficient gene editing in targeted tumor cells eventually. By carrying a combination of sgRNAs that targets STAT3 and RUNX1, the nanoRNP exhibited efficient gene expression disruptions on a heterogeneous tumor model with two subsets of cells whose proliferations were sensitive to the reduced expression of STAT3 and RUNX1, respectively, leading to the effective growth inhibition of the heterogeneous tumor. Considering the close relationship between tumor heterogeneity and cancer progression, resistance to therapy, and recurrences, nanoRNP provides a feasible strategy to overcome tumor heterogeneity in the development of more advanced cancer therapy against malignant tumors.


Asunto(s)
Sistemas CRISPR-Cas , Edición Génica/métodos , Neoplasias/terapia , Animales , Línea Celular Tumoral , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Terapia Genética/métodos , Humanos , Ratones , Ratones Desnudos , Nanomedicina/métodos , Neoplasias/genética , Neoplasias/patología , Factor de Transcripción STAT3/genética
7.
Small ; : e1801865, 2018 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-30035856

RESUMEN

Confinement of urate oxidase with detoxifying enzymes into multienzyme architecture is an appealing approach for gout treatment due to its capability to decompose serum uric acid without generation of H2 O2 . However, most of these strategies involve chemical modifications to the enzymes and barely consider enhancing the stability of the multienzyme architectures particularly against proteolysis, which significantly dampened its catalytic activity and in vivo stability. Herein, a novel strategy to prepare multienzyme nanoclusters with highly uricolytic activity and enhanced stability is demonstrated. With the close proximation, catalase can effectively decompose the H2 O2 generated by uricase during uricolysis. Moreover, with a shell structure constructed with polyethylene glycol, the nanocluster achieves great performance in reducing the nonspecific serum protein adsorptions and proteases digestion, leading to an enhanced circulation time after the intravenous administration. Such complementary multienzyme nanoclusters realize the long-term therapeutic effect in the management of serum uric acid level, without any toxicity or undesired immune responses in vivo. This work mimics the synergistic effect of protein complex in nature and can be further developed to a general method for the construction of multienzyme nanoclusters, which provides new opportunities for utilizing therapeutic enzymes for the treatment of metabolic diseases.

8.
ScientificWorldJournal ; 2014: 670328, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25105165

RESUMEN

Quantum image recognition is a technology by using quantum algorithm to process the image information. It can obtain better effect than classical algorithm. In this paper, four different quantum algorithms are used in the three stages of palmprint recognition. First, quantum adaptive median filtering algorithm is presented in palmprint filtering processing. Quantum filtering algorithm can get a better filtering result than classical algorithm through the comparison. Next, quantum Fourier transform (QFT) is used to extract pattern features by only one operation due to quantum parallelism. The proposed algorithm exhibits an exponential speed-up compared with discrete Fourier transform in the feature extraction. Finally, quantum set operations and Grover algorithm are used in palmprint matching. According to the experimental results, quantum algorithm only needs to apply square of N operations to find out the target palmprint, but the traditional method needs N times of calculation. At the same time, the matching accuracy of quantum algorithm is almost 100%.


Asunto(s)
Algoritmos , Dermatoglifia , Reconocimiento de Normas Patrones Automatizadas/métodos , Inteligencia Artificial , Biometría , Medicina Legal , Humanos
9.
Sci Adv ; 10(6): eadk0716, 2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38324678

RESUMEN

Nanoparticle-based cancer immunotherapy has shown promising therapeutic potential in clinical settings. However, current research mainly uses nanoparticles as delivery vehicles but overlooks their potential to directly modulate immune responses. Inspired by the endogenous endoplasmic reticulum (ER) stress caused by unfolded/misfolded proteins, we present a rationally designed immunogenic cell death (ICD) inducer named NanoICD, which is a nanoparticle engineered for ER targeting and retention. By carefully controlling surface composition and properties, we have obtained NanoICD that can effectively accumulate in the ER, induce ER stress, and activate ICD-associated immune responses. In addition, NanoICD is generally applicable to various proteins and enzymes to further enhance the immunomodulatory capacity, exemplified by encapsulating catalase (CAT) to obtain NanoICD/CAT, effectively alleviated immunosuppressive tumor microenvironment and induced robust antitumor immune responses in 4T1-bearing mice. This work demonstrates engineered nanostructures' potential to autonomously regulate biological processes and provides insights into the development of advanced nanomedicines for cancer treatment.


Asunto(s)
Antineoplásicos , Nanopartículas , Neoplasias , Ratones , Animales , Neoplasias/tratamiento farmacológico , Muerte Celular Inmunogénica , Antineoplásicos/farmacología , Inmunoterapia , Nanopartículas/uso terapéutico , Línea Celular Tumoral , Microambiente Tumoral
10.
Theranostics ; 13(14): 4781-4801, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37771786

RESUMEN

Hitchhiking, a recently developed bio-inspired cargo delivery system, has been harnessed for diverse applications. By leveraging the interactions between nanoparticles and circulatory cells or proteins, hitchhiking enables efficient navigation through the vasculature while evading immune system clearance. Moreover, it allows for targeted delivery of nutrients to tissues, surveillance of the immune system, and pathogen elimination. Various synthetic nanomaterials have been developed to facilitate hitchhiking with circulatory cells or proteins. By combining the advantages of synthetic nanomaterials and circulatory cells or proteins, hitchhiking nanomaterials demonstrate several advantages over conventional vectors, including enhanced circulatory stability and optimized therapeutic efficacy. This review provides an overview of general strategies for hitchhiking, choices of cells and proteins, and recent advances of hitchhiking nanomaterials for biomedical applications.

11.
BMC Med Genomics ; 16(1): 307, 2023 11 30.
Artículo en Inglés | MEDLINE | ID: mdl-38037104

RESUMEN

BACKGROUND: ATP7B is a copper-transporting protein that contributes to the chemo-resistance of human cancer cells. It remains unclear what the molecular mechanisms behind ATP7B are in cancer, as well as its role in human pan-cancer studies. METHODS: Our study evaluated the differential expression of ATP7B in cancer and paracancerous tissues based on RNA sequencing data from the GTEx and TCGA. Kaplan-Meier and Cox proportional hazards regressions were used to estimate prognostic factors associated with ATP7B.The correlations between the expression of ATP7B and immune cell infiltration, tumor mutation burden, microsatellite instability and immune checkpoint molecules were analyzed. Co-expression networks and mutations in ATP7B were analyzed using the web tools. An analysis of ATP7B expression difference on drug sensitivity on tumor cells was performed using the CTRP, GDSC and CMap database. RESULTS: ATP7B expression differed significantly between cancerous and paracancerous tissues. The abnormal expression of ATP7B was linked to prognosis in LGG and KIRC. Infiltration of immune cells, tumor mutation burden, microsatellite instability and immunomodulators had all been linked to certain types of cancer. Cancer cells exhibited a correlation between ATP7B expression and drug sensitivity. CONCLUSION: ATP7B might be an immunotherapeutic and prognostic biomarker based on its involvement in cancer occurrence and development.


Asunto(s)
Inestabilidad de Microsatélites , Neoplasias , Humanos , Inmunoterapia , Neoplasias/genética , Neoplasias/terapia , Adyuvantes Inmunológicos , Bases de Datos Factuales , Pronóstico
12.
ACS Nano ; 17(22): 22399-22409, 2023 11 28.
Artículo en Inglés | MEDLINE | ID: mdl-37930191

RESUMEN

Precise delivery of radionuclides and anticancer drugs to tumor tissue is crucial to ensuring drug synergism and optimal therapeutic effects in radionuclide-based combination radio-chemotherapy. However, current codelivery vectors often rely on physical embedment/adsorption to load anticancer drugs, which lacks precise mechanisms for drug loading and release, resulting in unpredictable combination effects. Herein, a macrocyclic-albumin conjugate (MAC) that enables precise loading and controlled release of anticancer drugs is presented. By conjugating multiple macrocyclic hosts (sulfonate azocalix[4]arenes, SAC4A) to albumin molecules, the MAC facilitates the precise loading of anticancer drugs through host-guest interactions and site-specific labeling of radionuclides. Furthermore, the MAC degrades under hypoxic conditions, enabling the release of loaded drugs upon reaching tumor tissues. Through precise loading and targeted delivery of radionuclides and anticancer drugs, MAC achieves efficient cancer diagnosis and combined radio-chemotherapy in breast cancer cell (4T1)-bearing mice. Considering that SAC4A can load many anticancer drugs, MAC may provide a promising platform for effective combination radio-chemotherapy.


Asunto(s)
Antineoplásicos , Nanopartículas , Neoplasias , Animales , Ratones , Sistemas de Liberación de Medicamentos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Albúminas , Sinergismo Farmacológico
13.
Front Nutr ; 10: 1168849, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37810921

RESUMEN

Objectives: This study analyzed the physical growth of small for gestational age (SGA) and appropriate for gestational age (AGA) twins up to one year after birth. Methods: Weight, length, and head circumference data of 0-1 year-old twins were collected from the Child Health Care System from 2010 to 2019. Physical data were presented as Z-scores. Five parameters - growth level of weight, body length, head circumference, growth velocity, and body proportion (weight for length) were compared in twins. Results: A total of 3,909 cases were collected (22.61% SGA, 77.39% AGA). 1. In both groups, WAZ (Weight for age z-score), HCZ (Head circumference for age z-score), and LAZ (Length for age z-score) increased more rapidly in the first 6 months. By one year of age, WAZ, HCZ, and LAZ had reached the normal range, but none had reached the average level of normal singleton children. 2. The mean values of WAZ, HCZ, and LAZ in the AGA group were between -1 and 0, and between -2 and - 1 in the SGA group, in the first year after birth. The SGA group lagged significantly behind the AGA group. The LAZ score of SGA and AGA was lower than the WAZ and HCZ scores. 3. The proportion of preterm AGA was the largest in twins, and the growth rate of preterm AGA was the fastest. Preterm twins had greater growth potential than term twins. However, the growth level of preterm SGA was always low. 4. The WFLZ (Weight for length z-score) in each group was approximately close to 0. The WFLZ of SGA was smaller than that of AGA twins at most time points. After 4 months of age, the WFLZ of twins had a downward trend. The WFLZ of preterm SGA approached -1 at approximately 1 year old. Conclusion: The physical growth of SGA and AGA in twins in the first year can reach the normal range but cannot reach the average level of normal singleton children. More attention should be paid to SGA in twins, especially preterm SGA. We should give proper nutritional guidance after 4 months of age to ensure the appropriate body proportion (weight for length) of SGA in twins. Clinical trial registration: www.chictr.org.cn, CTR2000034761.

14.
Zhongguo Dang Dai Er Ke Za Zhi ; 14(7): 481-4, 2012 Jul.
Artículo en Zh | MEDLINE | ID: mdl-22809596

RESUMEN

OBJECTIVE: To evaluate birth weights (BW) in late preterm infants (LPI) with different gestational ages (GA) and their physical growths at correct ages (CA) 1, 3 and 6 months. METHODS: A total of 287 LPIs were recruited for a cohort study between May 2010 and September 2011. Birth weights (BW) in infants with different gestational ages and their physical growths at CA 1, 3 and 6 months were evaluated. RESULTS: Of the 287 LPIs, mean BW in LPIs with gestational ages of 34-34(+6) and 35-35(+6) weeks was significantly lower than the reference value from a physical growth investigation on newborns of 15 cities of China in 1986 (P<0.05). However, mean BW in singleton LPIs (n=128) with gestational ages of 36-36(+6) weeks was significantly higher than the reference value (P<0.05). At CA 1, 3 and 6 months, more than 90% LPIs reached P(3) level in weights for age, length for age and head circumference for age. At CA 1 and 3 months, weight for age and head circumference for age in the LPIs were statistically higher than the reference values of physical growth in children under 7 years from nine cities of china in 2005 (P<0.05). Mean length for age at CA 1, 3 and 6 months was not significantly different from the reference value. CONCLUSIONS: There are obvious differences in BW in the LPIs compared with the reference value from a physical growth investigation on newborns of 15 cities of China in 1986, suggesting that the reference value of BW at different gestational ages needs to be updated in a certain interval. Before CA 6 months, there is a risk of overweight in LPIs and long-term monitoring is necessary. Growth of length should be followed-up for a long time.


Asunto(s)
Recien Nacido Prematuro/crecimiento & desarrollo , Peso al Nacer , Estatura , Femenino , Humanos , Recién Nacido , Masculino , Estudios Prospectivos , Valores de Referencia
15.
Medicine (Baltimore) ; 101(52): e32553, 2022 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-36596083

RESUMEN

RATIONALE: Rosai Dorfman disease is a rare benign histiocytoproliferative disorder that occurs in the intracranial area, which occurrs typically in lymph nodes. Extrapnodal Rosai Dorfman disease rarely develops in the central nervous system and is often a focal lesion based on the dura. Based on imaging and clinical symptoms, RDD may be misdiagnosed as meningioma, and some lesions can also occur in the brain parenchyma. In the case of benign disease, the final diagnosis is made by pathological tissue diagnosis. For chronic diseases, progression may be chronic or remitting and relapsing. PATIENT CONCERNS: A 54-years-old man was hospitalized after experiencing paroxic convulsions and being unconsciousness. A head magnetic resonance imaging demonstrates a strip of lesions in the right parietal lobe. No obvious abnormality is found in the laboratory data. DIAGNOSES: We diagnosed meningioma of right parietal lobe and secondary epilepsy, and prescribed oral sodium valproate to treat him. INTERVENTIONS: The lesion is located in the right parietal lobe on neuroimaging prior to surgery, which was taken for immunohistochemical examination. OUTCOMES: If it is found that immunohistochemistry reveals histiocytes are positive for CD68, S-100, but negative for CD1a, it is identified as RDD. For patients who are seizure-free following surgery, symptomatic management is used. Following parietal lesion resection, patients are seizure-free during the follow-up period (44 months). LESSONS: Basing on studying and summarizing relevant literatures, RDD is described in the report in terms of its diagnosis, pathology, treatment, and clinical outcome, in order to improve the diagnosis and identification of intracranial RDD by physicians.


Asunto(s)
Epilepsia , Histiocitosis Sinusal , Neoplasias Meníngeas , Meningioma , Humanos , Masculino , Persona de Mediana Edad , Histiocitosis Sinusal/complicaciones , Histiocitosis Sinusal/diagnóstico , Histiocitosis Sinusal/patología , Meningioma/diagnóstico , Diagnóstico Diferencial , Epilepsia/etiología , Epilepsia/complicaciones , Convulsiones/diagnóstico , Neoplasias Meníngeas/diagnóstico
16.
Int J Immunopathol Pharmacol ; 36: 3946320221104548, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35609253

RESUMEN

OBJECTIVES: Glioma is a common type of brain tumor with high incidence and mortality rates. Procollagen C-protease enhancer protein (PCOLCE) has been shown to regulate tumor growth and metastasis in several cancers. However, the role of PCOLCE in glioma is unknown. This study aims to assess the association between PCOLCE and prognosis of glioma, and investigated the potential mechanisms. METHODS: The prognostic value of PCOLCE was determined using data from nine publicly available glioma cohorts. We also investigated the relationship between PCOLCE and glioma immune microenvironment and predicted response to immunotherapy based on the expression levels of PCOLCE. The potential roles of PCOLCE in glioma were also explored and validated in cell experiment. RESULTS: Survival analysis suggested that high-PCOLCE expression was associated with poor prognosis in glioma. Upregulation of PCOLCE enhanced an immune suppressive microenvironment in glioma by regulating immunocyte infiltration and Cancer-Immunity Cycle. Cox and ROC analysis revealed that PCOLCE was a prognostic factor for glioma and could be used to predict survival of the patients. Patients with low-PCOLCE expression were more likely to respond to Immunotherapy with ICI (immune checkpoint inhibitor) and survive longer. Enrichment analysis showed that PCOLCE was associated with multiple tumor-related pathways. Finally, we demonstrated that the knockdown of PCOLCE inhibited glioma development by regulating cell cycle and promoting apoptosis in in vitro experiments. CONCLUSION: PCOLCE promotes glioma progression by regulating multiple tumor-related pathways and immune microenvironment and can be used as a prognostic factor for glioma.


Asunto(s)
Neoplasias Encefálicas , Glioma , Biomarcadores de Tumor/genética , Humanos , Péptido Hidrolasas , Procolágeno/metabolismo , Pronóstico , Microambiente Tumoral
17.
Adv Healthc Mater ; 11(14): e2200371, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35460333

RESUMEN

Efficient delivery of biomacromolecules or drugs across the cell membrane via endocytosis usually encounters inevitable entrapment in endosomes and subsequent degradation in lyso-endosomes. To address this issue, a series of arginine-rich cell penetrating polymers is designed and synthesized, which internalize into cells by inducing the formation of pores on the cell membrane, thereby crossing the cell membrane via direct translocation that fundamentally avoids endo/lysosomal entrapment. The structure-activity relationship studies show that PTn-R2-C6, which is a type of polymer that has two arginine residues and a flexible hexanoic acid linker in each side chain, exhibits excellent pore-formation ability on the cell membrane. Further investigations indicate that PTn-R2-C6 rapidly transports plasmid DNAs into cytosol through a similar endocytosis-independent pathway, thereby achieving significantly higher transfection efficiency and lower cytotoxicity than the gold-standard transfection reagent PEI 25K. These results suggest the great potential of PTn-R2-C6 as a safe and efficient gene transfection reagent for wide applications including disease treatments, vaccine development, and biomedical research purposes.


Asunto(s)
Arginina , Polímeros , Membrana Celular/metabolismo , Endosomas/metabolismo , Polímeros/metabolismo , Transfección
18.
Theranostics ; 12(8): 3747-3757, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35664058

RESUMEN

Rationale: In combination chemotherapy, the molar ratio of drugs is a critical parameter that determines the synergistic effects. However, most co-delivery vectors are incapable of maintaining the optimal molar ratio of drugs throughout the delivery process. Herein, a calixarene-modified albumin (CaMA), which can co-deliver multiple drugs with precise control of the drug ratio, is presented. Methods: CaMA was prepared by chemically conjugating multiple sulfonate azocalix[4]arenes (SAC4A) onto the surface of bovine serum albumin (BSA). The precise drug loading and synchronous drug release were measured using fluorescence spectroscopy. Mouse tumor cell 4T1 and 4T1-bearing mice were used to evaluate the combined effects of mitomycin C (MMC) and doxorubicin (DOX) in vitro and in vivo. Results: With multiple hypoxia-responsive calixarenes conjugated onto a single albumin molecule, CaMA achieved precise drug loading and synchronous release of multiple drugs into the tumor microenvironment. This unique drug loading and release mechanism ensures that CaMA maintains the drug ratio from the initial drug loading to the release site, providing a solid foundation for multi-drug combination therapy with the goal of achieving predictable therapeutic outcomes in vivo. The delivery of the model drug combination MMC and DOX at a prescreened ratio via CaMA achieved significantly enhanced tumor suppression and reduced systemic toxicity. Conclusions: This stoichiometric delivery feature makes CaMA a powerful tool for the development of combination chemotherapy and personalized medications for cancer treatment.


Asunto(s)
Calixarenos , Nanopartículas , Animales , Línea Celular Tumoral , Doxorrubicina , Combinación de Medicamentos , Sistemas de Liberación de Medicamentos/métodos , Quimioterapia Combinada , Ratones , Nanopartículas/química , Preparaciones Farmacéuticas , Albúmina Sérica Bovina/química
19.
Adv Mater ; 34(23): e2201945, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35385590

RESUMEN

Antimicrobial peptides (AMPs) hold great potential for use in tumor treatment. However, developing AMP-based antitumor therapies is challenging due to circulatory instability, hemolytic toxicity, low selectivity, and poor cell permeability of AMPs. In this study, a polymeric carrier for AMPs (denoted as PAMPm -co-PPBEn /PCA) is presented that effectively enhances their anticancer efficacy while minimizing their potential side effects. By integrating multiple responsive structures at the molecular level, the carrier finely controls the spatial distribution of AMPs in different biological microenvironments, thereby effectively modulating their membranolytic ability. Upon employing KLA as the model AMP, the polymeric carrier's hemolytic toxicity during blood circulation is suppressed, its cellular internalization when reaching tumor tissues facilitated, and its membranolytic toxicity toward the mitochondria upon entering cancer cells restored and further enhanced. Animal studies indicate that this approach significantly improves the antitumor efficacy of KLA and reduces its toxicity. Considering that the loading method for most AMPs is identical to that of KLA, the polymeric carrier reported in this study may provide a feasible approach for the development of AMP-based cancer treatments.


Asunto(s)
Péptidos Catiónicos Antimicrobianos , Neoplasias , Animales , Péptidos Catiónicos Antimicrobianos/farmacología , Péptidos Antimicrobianos , Neoplasias/tratamiento farmacológico , Polímeros/química
20.
Adv Mater ; 34(3): e2107161, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34767279

RESUMEN

The release of tumor-associated antigens (TAAs) and their cross-presentation in dendritic cells (DCs) are crucial for radio-immunotherapy. However, the irradiation resistance of tumor cells usually results in limited TAA generation and release. Importantly, TAAs internalized by DCs are easily degraded in lysosomes, resulting in unsatisfactory extent of TAA cross-presentation. Herein, an antigen-capturing stapled liposome (ACSL) with a robust structure and bioactive surface is developed. The ACSLs capture and transport TAAs from lysosomes to the cytoplasm in DCs, thereby enhancing TAA cross-presentation. l-arginine encapsulated in ACSLs induces robust T cell-dependent antitumor response and immune memory in 4T1 tumor-bearing mice after local irradiation, resulting in significant tumor suppression and an abscopal effect. Replacing l-arginine with radiosensitizers, photosensitizers, and photothermal agents may make ACSL a universal platform for the rapid development of various combinations of anticancer therapies.


Asunto(s)
Reactividad Cruzada , Liposomas , Animales , Antígenos de Neoplasias , Células Dendríticas , Inmunoterapia/métodos , Liposomas/metabolismo , Ratones
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