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1.
Sci Rep ; 14(1): 5095, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429374

RESUMO

The clinical application of conventional doxorubicin (CDOX) was constrained by its side effects. Liposomal doxorubicin was developed to mitigate these limitations, showing improved toxicity profiles. However, the adverse events associated with liposomal doxorubicin and CDOX have not yet been comprehensively evaluated in clinical settings. The FAERS data from January 2004 to December 2022 were collected to analyze the adverse events of liposomal doxorubicin and CDOX. Disproportionate analysis and Bayesian analysis were employed to quantify this association. Our analysis incorporated 68,803 adverse event reports related to Doxil/Caelyx, Myocet and CDOX. The relative odds ratios (RORs, 95%CI) for febrile neutropenia associated with CDOX, Doxil/Caelyx, and Myocet were 42.45 (41.44; 43.48), 17.53 (16.02; 19.20), and 34.68 (26.63; 45.15) respectively. For cardiotoxicity, they were 38.87(36.41;41.49), 17.96 (14.10; 22.86), and 37.36 (19.34; 72.17). For Palmar-Plantar Erythrodysesthesia (PPE), the RORs were 6.16 (5.69; 6.68), 36.13 (32.60; 40.06), and 19.69 (11.59; 33.44). Regarding onset time, significant differences adverse events including neutropenia, PPE, pneumonia and malignant neoplasm progression. This study indicates that clinical monitoring for symptoms of cardiotoxicity of CDOX and Myocet, and PPE and interstitial lung disease of Doxil should be performed. Additionally, the onset time of febrile neutropenia, malignant neoplasm progression, and pneumonia associated with Doxil and Myocet merits particular attention. Continuous surveillance, risk evaluations, and additional comparative studies between liposomal doxorubicin and CDOX were recommended.


Assuntos
Doxorrubicina/análogos & derivados , Neoplasias , Neutropenia , Pneumonia , Humanos , Cardiotoxicidade/tratamento farmacológico , Teorema de Bayes , Doxorrubicina/efeitos adversos , Lipossomos , Neoplasias/tratamento farmacológico , Neutropenia/induzido quimicamente , Pneumonia/tratamento farmacológico , Polietilenoglicóis
2.
Int J Nanomedicine ; 19: 2039-2056, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38476274

RESUMO

Purpose: This study investigated the brain targeting mechanism of doxorubicin-loaded polybutyl cyanoacrylate (PBCA) nanoparticles, particularly their interactions with the blood-brain barrier (BBB). The BBB protects the brain from drugs in the bloodstream and represents a crucial obstacle in the treatment of brain cancer. Methods: An advanced computer model analyzed the brain delivery of two distinct formulations, Doxil® and surfactant-coated PBCA nanoparticles. Computational learning was combined with in vitro release and cell interaction studies to comprehend the underlying brain delivery pathways. Results: Our analysis yielded a surprising discovery regarding the brain delivery mechanism of PBCA nanoparticles. While Doxil® exhibited the expected behavior, accumulating in the brain through extravasation in tumor tissue, PBCA nanoparticles employed a unique and previously uncharacterized mechanism. They underwent cell hitchhiking, resulting in a remarkable more than 1000-fold increase in brain permeation rate compared to Doxil® (2.59 × 10-4 vs 0.32 h-1). Conclusion: The nonspecific binding to blood cells facilitated and intensified interactions of surfactant-coated PBCA nanoparticles with the vascular endothelium, leading to enhanced transcytosis. Consequently, the significant increase in circulation time in the bloodstream, coupled with improved receptor interactions, contributes to this remarkable uptake of doxorubicin into the brain.


Assuntos
Doxorrubicina/análogos & derivados , Embucrilato , Nanopartículas , Encéfalo/metabolismo , Barreira Hematoencefálica/metabolismo , Doxorrubicina/metabolismo , Nanopartículas/química , Tensoativos , Embucrilato/química , Portadores de Fármacos/química , Polietilenoglicóis
3.
Gan To Kagaku Ryoho ; 51(2): 149-152, 2024 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-38449400

RESUMO

Febrile neutropenia(FN)causes a prolonged treatment schedule and decreased relative dose intensity(RDI)during cancer chemotherapy, which adversely affects prognosis. In recent years, dose-dense(dd)chemotherapy has been used as adjuvant chemotherapy for patients with breast cancer based on the results of improved disease-free survival according to meta-analysis data. Regarding neoadjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer, taxanes and trastuzumab with the addition of pertuzumab have shown higher pathological complete response rates and elevated incidences of FN. One hundred seventy-six patients received pegfilgrastim(PEG)prophylaxis between January 2011 and January 2023. Until 2019, the median day of PEG prophylaxis was day 4 from chemotherapy completion(days 2- 3, 14 cases; day 4, 41 cases; and day 5, 8 cases)with antibiotic prophylaxis in 58 patients(92%). FN was observed in 19 cases(30%). The RDIs of TC and FEC were 96.8% and 96.0%, respectively. Meanwhile, the median day of PEG prophylaxis after 2020 was day 2 from chemotherapy completion(days 2-3, 108 cases; day 4, 4 cases; and day 5, 1 case)without antibiotic prophylaxis. FN was not observed in any of the cases. The RDI of all regimens was 99.7%. Although there were some differences in chemotherapy regimens, an earlier timing of PEG prophylaxis(especially 24-48 hours from chemotherapy completion)has been shown to reduce the incidence of FN and increase the RDI.


Assuntos
Neoplasias da Mama , Neutropenia Febril , Feminino , Humanos , Neoplasias da Mama/tratamento farmacológico , Neutropenia Febril/induzido quimicamente , Neutropenia Febril/prevenção & controle , Filgrastim/uso terapêutico , Polietilenoglicóis , Metanálise como Assunto
4.
Sci Rep ; 14(1): 6111, 2024 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-38480832

RESUMO

Remarkable resistance of bacterial biofilms to high doses of antimicrobials and antibiotics is one of their main challenges. Encapsulation of proteolytic enzymes is one of the suggested strategies to tackle this problem. In this regard, the antibacterial and anti-biofilm activity of biocompatible hyaluronic acid- Lysine nanogels containing serratiopeptidase (SRP-loaded HA-Lys nanogel) was assessed against P. aeruginosa and S. aureus strains. SRP-loaded HA-Lys nanogel was prepared using dropping method and optimized by Box-Behnken experimental design. These formulations were studied for physical characterization, release profile, stability, bioactivity, and anti-biofilm effects. The particle size, polydispersity index (PDI), and surface charge were measured by Zetasizer Nano ZS. The average particle size and zeta potential of the optimum sample were 156 nm and -14.1 mV, respectively. SRP release showed an initial burst followed by sustained release and the highest release was around 77%. Enzyme biological activity data revealed the higher efficiency of free SRP compared to SRP-loaded HA-Lys nanogel. The time-kill assay showed that both forms of SRP-loaded HA-Lys nanogel and blank HA-Lys nanogel showed significant antimicrobial activity against examined bacteria in comparison to the free enzyme. The obtained results demonstrated improved anti-biofilm efficacy and down regulation of tested biofilm genes for both SRP-loaded HA-Lys nanogel 100% and blank HA-Lys nanogel 100% compared to SRP 100%.


Assuntos
Ácido Hialurônico , Lisina , Polietilenoglicóis , Polietilenoimina , Nanogéis/química , Ácido Hialurônico/química , Lisina/farmacologia , Staphylococcus aureus/fisiologia , Peptídeo Hidrolases/farmacologia , Antibacterianos/farmacologia , Biofilmes
5.
J Nanobiotechnology ; 22(1): 109, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38481326

RESUMO

BACKGROUND: Immunogenic cell death (ICD) is a crucial approach to turn immunosuppressive tumor microenvironment (ITM) into immune-responsive milieu and improve the response rate of immune checkpoint blockade (ICB) therapy. However, cancer cells show resistance to ICD-inducing chemotherapeutic drugs, and non-specific toxicity of those drugs against immune cells reduce the immunotherapy efficiency. METHODS: Herein, we propose cancer cell-specific and pro-apoptotic liposomes (Aposomes) encapsulating second mitochondria-derived activator of caspases mimetic peptide (SMAC-P)-doxorubicin (DOX) conjugated prodrug to potentiate combinational ICB therapy with ICD. The SMAC-P (AVPIAQ) with cathepsin B-cleavable peptide (FRRG) was directly conjugated to DOX, and the resulting SMAC-P-FRRG-DOX prodrug was encapsulated into PEGylated liposomes. RESULTS: The SMAC-P-FRRG-DOX encapsulated PEGylated liposomes (Aposomes) form a stable nanostructure with an average diameter of 109.1 ± 5.14 nm and promote the apoptotic cell death mainly in cathepsin B-overexpressed cancer cells. Therefore, Aposomes induce a potent ICD in targeted cancer cells in synergy of SMAC-P with DOX in cultured cells. In colon tumor models, Aposomes efficiently accumulate in targeted tumor tissues via enhanced permeability and retention (EPR) effect and release the encapsulated prodrug of SMAC-P-FRRG-DOX, which is subsequently cleaved to SMAC-P and DOX in cancer cells. Importantly, the synergistic activity of inhibitors of apoptosis proteins (IAPs)-inhibitory SMAC-P sensitizing the effects of DOX induces a potent ICD in the cancer cells to promote dendritic cell (DC) maturation and stimulate T cell proliferation and activation, turning ITM into immune-responsive milieu. CONCLUSIONS: Eventually, the combination of Aposomes with anti-PD-L1 antibody results in a high rate of complete tumor regression (CR: 80%) and also prevent the tumor recurrence by immunological memory established during treatments.


Assuntos
Complexos Multienzimáticos , Neoplasias , Oligopeptídeos , Pró-Fármacos , Humanos , Pró-Fármacos/farmacologia , Pró-Fármacos/química , Catepsina B , Lipossomos , Doxorrubicina/farmacologia , Doxorrubicina/química , Imunoterapia , Neoplasias/tratamento farmacológico , Peptídeos , Polietilenoglicóis , Linhagem Celular Tumoral , Microambiente Tumoral
6.
Int J Mol Sci ; 25(5)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38474003

RESUMO

MicroRNA (miRNA) modulation has been identified as a promising strategy for improving the response of human prostate cancer (PCa) to radiotherapy (RT). Studies have shown that mimics or inhibitors of miRNAs could modulate the sensitivity of PCa cells to RT. In addition, pegylated gold nanoparticles have been studied as a therapeutic approach to treat PCa cells and/or vehicles for carrying miRNAs to the inside of cells. Therefore, we evaluated the capacity of hypofractionated RT and pegylated gold nanorods (AuNPr-PEG) to modulate the miRNA signature on PCa cells. Thus, RT-qPCR was used to analyze miRNA-95, miRNA-106-5p, miRNA-145-5p, and miRNA-541-3p on three human metastatic prostate cell lines (PC3, DU145, and LNCaP) and one human prostate epithelial cell line (HprEpiC, a non-tumor cell line) with and without treatment. Our results showed that miRNA expression levels depend on cell type and the treatment combination applied using RT and AuNPr-PEG. In addition, cells pre-treated with AuNPr-PEG and submitted to 2.5 Gy per day for 3 days decreased the expression levels of miRNA-95, miRNA-106, miRNA-145, and miRNA-541-3p. In conclusion, PCa patients submitted to hypofractionated RT could receive personalized treatment based on their metastatic cellular miRNA signature, and AuNPr-PEG could be used to increase metastatic cell radiosensitivity.


Assuntos
Nanopartículas Metálicas , MicroRNAs , Neoplasias da Próstata , Masculino , Humanos , MicroRNAs/genética , Ouro/metabolismo , Linhagem Celular Tumoral , Neoplasias da Próstata/metabolismo , Polietilenoglicóis/metabolismo , Regulação Neoplásica da Expressão Gênica
7.
Molecules ; 29(5)2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38474593

RESUMO

Lycorine is a kind of natural active ingredient with a strong antitumor effect. In this study, folate ligand-conjugated polyethylene glycol-block-poly(l-lactide) (PEG-PLLA) nanoparticles (FA-PEG-PLLA NPs) were designed to deliver lycorine to enhance its anti-glioma activity. The successful preparation of the FA-PEG-PLLA polymer was confirmed by 1H-NMR, FT-IR, XRD, TGA, and DSC. The optimal formulation for LYC@FA-PEG-PLLA NPs was determined by response surface analysis as follows: sodium dodecyl sulfate (SDS) of 1%, carrier material of 0.03 g, organic phase volume of 3 mL, and ultrasonic power of 20%. The LYC@FA-PEG-PLLA NPs exhibited an encapsulation efficiency of 83.58% and a particle size of 49.71 nm, demonstrating good stability. Hemolysis experiments, MTT assays, and cell scratch assays revealed excellent biocompatibility of FA-PEG-PLLA and superior anti-glioma activity of LYC@FA-PEG-PLLA NPs compared to the raw drug. Additionally, cell apoptosis assays, ROS experiments, and western blot analysis demonstrated that LYC@FA-PEG-PLLA NPs contributed to cell apoptosis by inducing ROS generation and increasing the expression of NF-κB inhibitory protein IκBα. These results suggested that LYC@FA-PEG-PLLA NPs hold promise for glioma treatment.


Assuntos
Alcaloides de Amaryllidaceae , Glioma , Nanopartículas , Fenantridinas , Humanos , Ácido Fólico/química , Espécies Reativas de Oxigênio , Espectroscopia de Infravermelho com Transformada de Fourier , Nanopartículas/química , Polietilenoglicóis/química , Portadores de Fármacos/química , Tamanho da Partícula , Linhagem Celular Tumoral
8.
Molecules ; 29(5)2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38474668

RESUMO

Anthracycline antibiotics, namely, doxorubicin (DOX) and daunorubicin, are among the most widely used anticancer therapies, yet are notoriously associated with severe myocardial damage due to oxidative stress and mitochondrial damage. Studies have indicated the strong pharmacological properties of Berberine (Brb) alkaloid, predominantly mediated via mitochondrial functions and nuclear networks. Despite the recent emphasis on Brb in clinical cardioprotective studies, pharmaceutical limitations hamper its clinical use. A nanoformulation for Brb was developed (mMic), incorporating a cationic lipid, oleylamine (OA), into the TPGS-mixed corona of PEGylated-phosphatidylethanolamine (PEG-PE) micelles. Cationic TPGS/PEG-PE mMic with superior Brb loading and stability markedly enhanced both intracellular and mitochondria-tropic Brb activities in cardiovascular muscle cells. Sub-lethal doses of Brb via cationic OA/TPGS mMic, as a DOX co-treatment, resulted in significant mitochondrial apoptosis suppression. In combination with an intense DOX challenge (up to ~50 µM), mitochondria-protective Brb-OA/TPGS mMic showed a significant 24 h recovery of cell viability (p ≤ 0.05-0.01). Mechanistically, the significant relative reduction in apoptotic caspase-9 and elevation of antiapoptotic Bcl-2 seem to mediate the cardioprotective role of Brb-OA/TPGS mMic against DOX. Our report aims to demonstrate the great potential of cationic OA/TPGS-mMic to selectively enhance the protective mitohormetic effect of Brb to mitigate DOX cardiotoxicity.


Assuntos
Berberina , Doenças Mitocondriais , Fosfatidiletanolaminas , Polietilenoglicóis , Humanos , Micelas , Berberina/farmacologia , Cardiotoxicidade/tratamento farmacológico , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Vitamina E/farmacologia , Apoptose , Doenças Mitocondriais/tratamento farmacológico
9.
Nutrients ; 16(5)2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38474776

RESUMO

A low total plasma vitamin B12 supports a clinical suspicion of B12 deficiency, while the interpretation of an unexpectedly normal/high level is marred by controversies. Here, we critically review current knowledge on B12 in blood plasma, including the presence of the so-called "macro-B12". The latter form is most often defined as the fraction of B12 that can be removed by precipitation with polyethylene glycol (PEG), a nonspecific procedure that also removes protein polymers and antibody-bound analytes. Plasma B12 includes B12 attached to transcobalamin and haptocorrin, and an increased concentration of one or both proteins almost always causes an elevation of B12. The total plasma B12 is measured by automated competitive binding assays, often incorrectly referred to as immunoassays, since the binding protein is intrinsic factor and not an antibody. An unexpectedly high level of B12 may be further explored using immunological measurements of haptocorrin and transcobalamin (optionally combined with e.g., size-exclusion chromatography). Nonspecific methods, such as PEG precipitation, are likely to give misleading results and cannot be recommended. Currently, the need for evaluation of a high B12 of unknown etiology is limited since other tests (such as measurements of methylmalonic acid) may better guide the diagnosis of B12 deficiency.


Assuntos
Transcobalaminas , Deficiência de Vitamina B 12 , Humanos , Transcobalaminas/análise , Vitamina B 12 , Anticorpos/metabolismo , Polietilenoglicóis , Polímeros/metabolismo , Deficiência de Vitamina B 12/diagnóstico
10.
Medicine (Baltimore) ; 103(10): e37424, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38457582

RESUMO

Chronic kidney disease (CKD) and gout commonly co-occur. Pegloticase lowers serum urate (SU) in uncontrolled gout patients but antidrug antibodies limit urate-lowering response and increase infusion reaction (IR) risk. Methotrexate (MTX) co-administration increases pegloticase response rate and mitigates IR risk but CKD limits MTX use. This pooled case series examined pegloticase + MTX co-therapy in uncontrolled gout patients with and without CKD. Cases of pegloticase + MTX co-therapy in existing datasets were retrospectively examined. Baseline eGFR classified patients as CKD (eGFR < 60 mL/min/1.73 m2) or non-CKD (eGFR ≥ 60 mL/min/1.73 m2). Patient characteristics, treatment parameters, laboratory values, urate-lowering response rate (≥12 pegloticase infusions received and SU < 6 mg/dL just before infusion 12), and AEs were examined. Fifteen CKD (eGFR: 43.2 ±â€…11.3 mL/min/1.73 m2; SU: 8.6 ±â€…2.2 mg/dL), 27 non-CKD (eGFR: 82.9 ±â€…19.0 mL/min/1.73 m2; SU: 9.5 ±â€…1.7 mg/dL) patients were included. Comorbidity profiles were similar, but CKD patients were older (72.0 ±â€…9.9 vs 52.3 ±â€…14.3 years) and more often female (33.3% vs 7.4%). Treatment parameters were similar with 4-week MTX Run-in followed by mean of 14.7 ±â€…8.1 [CKD] vs 14.1 ±â€…7.1 [non-CKD] pegloticase infusions. However, CKD patients had lower MTX dose (14.8 ±â€…5.8 vs 19.3 ±â€…4.9 mg/week). Urate-lowering response was similar (92% vs 86%). eGFR increased during treatment in 60% of CKD (+11.5 ±â€…20.9 mL/min/1.73 m2, 87% stable/improved CKD-stage) and 44% of non-CKD (+4.2 ±â€…15.0 mL/min/1.73 m2) patients. AEs were similar (≥1 AE CKD: 53%, non-CKD: 67%; gout flare most-reported). One case each of pancytopenia and IR (mild) occurred in non-CKD patients. These real-world data show similar pegloticase + MTX efficacy in CKD and non-CKD patients. No new safety signals were identified, with most CKD patients showing renal function stability or improvement during therapy.


Assuntos
Gota , Insuficiência Renal Crônica , Urato Oxidase , Humanos , Feminino , Gota/complicações , Gota/tratamento farmacológico , Ácido Úrico , Metotrexato/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento , Exacerbação dos Sintomas , Polietilenoglicóis , Supressores da Gota/uso terapêutico , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/induzido quimicamente
11.
Signal Transduct Target Ther ; 9(1): 62, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448403

RESUMO

Natural killer T cell lymphoma (NKTCL) is highly aggressive, with advanced stage patients poorly responding to intensive chemotherapy. To explore effective and safe treatment for newly diagnosed advanced stage NKTCL, we conducted a phase II study of anti-metabolic agent pegaspargase plus PD-1 antibody sintilimab (NCT04096690). Twenty-two patients with a median age of 51 years (range, 24-74) were enrolled and treated with induction treatment of pegaspargase 2500 IU/m2 intramuscularly on day 1 and sintilimab 200 mg intravenously on day 2 for 6 cycles of 21 days, followed by maintenance treatment of sintilimab 200 mg for 28 cycles of 21 days. The complete response and overall response rate after induction treatment were 59% (95%CI, 43-79%) and 68% (95%CI, 47-84%), respectively. With a median follow-up of 30 months, the 2 year progression-free and overall survival rates were 68% (95%CI, 45-83%) and 86% (95%CI, 63-95%), respectively. The most frequently grade 3/4 adverse events were neutropenia (32%, n = 7) and hypofibrinogenemia (18%, n = 4), which were manageable and led to no discontinuation of treatment. Tumor proportion score of PD-L1, peripheral blood high-density lipoprotein cholesterol, and apolipoprotein A-I correlated with good response, while PD-1 on tumor infiltrating lymphocytes and peripheral Treg cells with poor response to pegaspargase plus sintilimab treatment. In conclusion, the chemo-free regimen pegaspargase plus sintilimab was effective and safe in newly diagnosed, advanced stage NKTCL. Dysregulated lipid profile and immunosuppressive signature contributed to treatment resistance, providing an alternative therapeutic approach dual targeting fatty acid metabolism and CTLA-4 in NKTCL.


Assuntos
Anticorpos Monoclonais Humanizados , Asparaginase , Linfoma , Células T Matadoras Naturais , Polietilenoglicóis , Humanos , Receptor de Morte Celular Programada 1 , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem
12.
J Environ Pathol Toxicol Oncol ; 43(2): 29-42, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38505911

RESUMO

Withaferin A (WA) is a natural steroidal lactone with promising pharmacological activities, but its poor solubility and bioavailability hinder its clinical application. The liposomal drug delivery system has attracted considerable attention to overcome the delivery limitations of pharmacological agents. The present study investigated the effect of WA-loaded pegylated nanoliposomes (LWA) on in vitro and in vivo B16F10 melanoma tumor models. In vitro results showed that LWA had significantly (P < 0.01) higher cytotoxicity than free WA and induced ROS-mediated apoptosis in B16F10 cells. Transwell cell migration and invasion studies demonstrated that LWA treatment significantly (P < 0.01) decreased the migratory and invasive capacities of melanoma cells compared with WA. In vivo study revealed that treatment significantly (P < 0.01) reduced tumor growth in experimental animals compared with WA or tumor control. Also, LWA administration remarkably inhibited tumor cell proliferation by downregulating the expression of Ki-67 and Cyclin D1 and induced apoptosis by regulating the expression of Bax, Bcl2, and Bcl xl levels. Our results strongly suggest that LWA could be a promising therapeutic formulation for treating malignant melanoma.


Assuntos
Melanoma Experimental , Melanoma , Vitanolídeos , Animais , Camundongos , Melanoma/tratamento farmacológico , Linhagem Celular Tumoral , Apoptose , Polietilenoglicóis/farmacologia , Polietilenoglicóis/uso terapêutico , Melanoma Experimental/tratamento farmacológico
13.
Colloids Surf B Biointerfaces ; 236: 113795, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38428207

RESUMO

Overexpression of epidermal growth factor receptor (EGFR) in cancer is a key cause of recurrence of cervical cancer (CC). Although the EGF-EGFR pathway has been studied for decades, preventing tumor growth and recurrence caused by peripheral EGF remains a great challenge. In this work, a strategy is proposed to reduce the stimulation of high concentration EGF on tumor growth by using a thermo-sensitive hydrogel. The hydrogel is a triblock copolymer composed of polyethylene glycol (PEG) and poly (lactide glycolide) (PLGA). Based on the excellent temperature sensitivity, carrier capacity, swelling property and biocompatibility, the hydrogel can absorb the liquid around the tumor by injection and release EGF continuously at low concentration. The inhibitory effect of hydrogel on tumor growth is fully confirmed by an implanted tumor mouse model with human cervical cancer cell lines (HeLa) using triple-immunodeficient NCG mice. Compared with free EGF, the EGF-loaded hydrogel can hardly induce surface plasmon resonance (SPR) response, which proves that hydrogel can effectively weaken cytoskeleton rearrangement and inhibit cell migration by continuously releasing low concentration EGF. In addition, the EGF-loaded hydrogel can reduce cell proliferation by delaying the progress of cell cycle progression. Taken together, the hydrogel can effectively protect tumor microenvironment from the stimulation of high concentration EGF, delay cancer cellular processes and tumor growth, and thus providing an approach for inhibiting tumor recurrence of CC.


Assuntos
Poliésteres , Neoplasias do Colo do Útero , Feminino , Camundongos , Humanos , Animais , Neoplasias do Colo do Útero/tratamento farmacológico , Fator de Crescimento Epidérmico , Preparações de Ação Retardada , Polietilenoglicóis , Hidrogéis/farmacologia , Materiais Biocompatíveis , Células HeLa , Receptores ErbB , Microambiente Tumoral
14.
Colloids Surf B Biointerfaces ; 236: 113804, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38428209

RESUMO

In this study, a double network (DN) hydrogel was synthesized using poly(ethylene glycol) diacrylate (PEGDA) and sodium alginate (SA), incorporating copper-doped mesoporous silica nanospheres (Cu-MSNs) and zinc oxide nanoparticles (ZnO NPs). The blending of PEGDA and SA (PS) facilitates the double network and improves the less porous microstructure of pure PEGDA hydrogel. Furthermore, the incorporation of ZnO NPs and Cu-MSNs into the hydrogel network (PS@ZnO/Cu-MSNs) improved the mechanical properties of the hydrogel (Compressive strength = ⁓153 kPa and Young's modulus = ⁓ 1.66 kPa) when compared to PS hydrogel alone (Compressive strength = ⁓ 103 kPa and Young's modulus = ⁓ 0.95 kPa). In addition, the PS@ZnO/Cu-MSNs composite hydrogel showed antibacterial activities against Staphylococcus aureus and Escherichia coli. Importantly, the PS@ZnO/Cu-MSNs hydrogel demonstrated excellent biocompatibility, enhanced MC3T3-E1 cell adhesion, proliferation, and significant early-stage osteoblastic differentiation, as evidenced by increased alkaline phosphatase (ALP), and improved calcium mineralization, as evidenced by increased alizarin red staining (ARS) activities. These findings point to the possible use of the PS@ZnO/Cu-MSNs composite hydrogel in bone tissue regeneration.


Assuntos
Nanopartículas , Nanosferas , Óxido de Zinco , Nanosferas/química , Cobre/farmacologia , Óxido de Zinco/farmacologia , Osteogênese , Engenharia Tecidual , Hidrogéis/farmacologia , Hidrogéis/química , Dióxido de Silício/química , Alginatos/farmacologia , Alginatos/química , Nanopartículas/química , Polietilenoglicóis/química
15.
STAR Protoc ; 5(1): 102924, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38430518

RESUMO

In addition to proteins, microRNAs, and lipids, plant-derived exosome-like nanovesicles (ENVs) are also enriched with host plant bioactives. Both curcumin and piperine are water insoluble, lack bioavailability, and are extracted by non-ecofriendly solvents. Herein, we present an eco-friendly protocol for co-isolating both curcumin and piperine in the form of hybrid ENVs. We describe steps for sample pre-processing, combined homogenization of plant materials, filtration, and differential centrifugation. We then detail procedures for polyethylene glycol-based fusion and precipitation of hybrid ENVs. For complete details on the use and execution of this protocol, please refer to Kumar et al.1.


Assuntos
Alcaloides , Curcuma , Curcumina , Piperidinas , Alcamidas Poli-Insaturadas , Polietilenoglicóis , Benzodioxóis
16.
ACS Nano ; 18(11): 7825-7836, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38452271

RESUMO

Lipid nanoparticles (LNPs), a nonviral nucleic acid delivery system, have shown vast potential for vaccine development and disease treatment. LNPs assist mRNA to cross physiological barriers such as cell membranes and endosomes/lysosomes, promoting the intracellular presentation of mRNA. However, the endosome escape efficiency and biosafety of currently commercialized LNPs are still unsatisfactory, resulting in underutilization of mRNA. Herein, we report that fluorinated modification of the 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol)-2000 (PEG-DSPE), termed as FPD, in the LNPs can improve the delivery efficiency of mRNA. FPD accounts for only 1.5% of lipids in LNPs but could mediate a 5-fold and nearly 2-fold enhancement of mRNA expression efficiency in B16F10 tumor cells and primary dendritic cells, respectively. Mechanism studies reveal that FPD promotes the cellular internalization of LNPs as well as endosome escape. In vivo studies substantiate that FPD can augment overall mRNA expression at least 3-fold, either by intravenous or intraperitoneal injection, compared to LNPs prepared with nonfluorinated PEG-lipids at a relatively low mRNA dose. Besides, with the introduction of FPD, mRNA expression in the spleen augmented compared to that of the DMG-PEG commercial formulations. Benefiting from a prudent dosage of fluorine, the fluorinated LNPs display favorable biosafety profiles at cellular and zoological levels.


Assuntos
Lipídeos , Nanopartículas , Polietilenoglicóis , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Lipossomos , Nanopartículas/metabolismo , RNA Interferente Pequeno
17.
Colloids Surf B Biointerfaces ; 236: 113828, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38452625

RESUMO

Despite the success of polyethylene glycol-based (PEGylated) polyesters in the drug delivery and biomedical fields, concerns have arisen regarding PEG's immunogenicity and limited biodegradability. In addition, inherent limitations, including limited chemical handles as well as highly hydrophobic nature, can restrict their effectiveness in physiological conditions of the polyester counterpart. To address these matters, an increasing amount of research has been focused towards identifying alternatives to PEG. One promising strategy involves the use of bio-derived polyols, such as glycerol. In particular, glycerol is a hydrophilic, non-toxic, untapped waste resource and as other polyols, can be incorporated into polyesters via enzymatic catalysis routes. In the present study, a systematic screening is conducted focusing on the incorporation of 1,6-hexanediol (Hex) (hydrophobic diol) into both poly(glycerol adipate) (PGA) and poly(diglycerol adipate) (PDGA) at different (di)glycerol:hex ratios (30:70; 50:50 and 70:30 mol/mol) and its effect on purification upon NPs formation. By varying the amphiphilicity of the backbone, we demonstrated that minor adjustments influence the NPs formation, NPs stability, drug encapsulation, and degradation of these polymers, despite the high chemical similarity. Moreover, the best performing materials have shown good biocompatibility in both in vitro and in vivo (whole organism) tests. As preliminary result, the sample containing diglycerol and Hex in a 70:30 ratio, named as PDGA-Hex 30%, has shown to be the most promising candidate in this small library analysed. It demonstrated comparable stability to the glycerol-based samples in various media but exhibited superior encapsulation efficiency of a model hydrophobic dye. This in-depth investigation provides new insights into the design and modification of biodegradable (di)glycerol-based polyesters, potentially paving the way for more effective and sustainable PEG-free drug delivery nano-systems in the pharmaceutical and biomedical fields.


Assuntos
Nanopartículas , Poliésteres , Poliésteres/química , Glicerol/química , Polietilenoglicóis/química , Sistemas de Liberação de Medicamentos , Preparações Farmacêuticas , Adipatos , Nanopartículas/química
18.
Anal Chim Acta ; 1299: 342449, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38499430

RESUMO

Antifouling biosensors capable of preventing protein nonspecific adhesion in real human bodily fluids are highly sought-after for precise disease diagnosis and treatment. In this context, an enhanced split-type photoelectrochemical (PEC) aptasensor was developed incorporating a four-armed polyethylene glycol (4A-PEG) to construct a robust antifouling coating, enabling accurate and sensitive bioanalysis. The split-type PEC system involved the photoelectrode and the biocathode, effectively separating signal converter with biorecogniton events. Specifically, the TiO2 electrode underwent sequential modification with ZnIn2S4 (ZIS) and polydopamine (PDA) to form the PDA/ZIS/TiO2 photoelectrode. The cathode substrate was synthesized as a hybrid of N-doped graphene loaded with Pt nanoparticles (NG-Pt), and subsequently modified with 4A-PEG to establish a robust antifouling coating. Following the anchoring of probe DNA (pDNA) on the 4A-PEG-grafted antifouling coating, the biocathode for model target of cancer antigen 125 (CA125) was obtained. Leveraging pronounced photocurrent output of the photoelectrode and commendable antifouling characteristics of the biocathode, the split-type PEC aptasensor showcased exceptional detection performances with high sensitivity, good selectivity, antifouling ability, and potential feasibility.


Assuntos
Incrustação Biológica , Técnicas Biossensoriais , Humanos , Polietilenoglicóis , Incrustação Biológica/prevenção & controle , Técnicas Eletroquímicas , Processos Fotoquímicos
19.
Bioconjug Chem ; 35(3): 351-370, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38440876

RESUMO

A cationic, dendrimer-like oligo(aminoamide) carrier with four-arm topology based on succinoyl tetraethylene pentamine and histidines, cysteines, and N-terminal azido-lysines was screened for plasmid DNA delivery on various cell lines. The incorporated azides allow modification with various shielding agents of different polyethylene glycol (PEG) lengths and/or different ligands by copper-free click reaction, either before or after polyplex formation. Prefunctionalization was found to be advantageous over postfunctionalization in terms of nanoparticle formation, stability, and efficacy. A length of 24 ethylene oxide repetition units and prefunctionalization of ≥50% of azides per carrier promoted optimal polyplex shielding. PEG shielding resulted in drastically reduced DNA transfer, which could be successfully restored by active lectin targeting via novel GalNAc or mannose ligands, enabling enhanced receptor-mediated endocytosis of the carrier system. The involvement of the asialoglycoprotein receptor (ASGPR) in the uptake of GalNAc-functionalized polyplexes was confirmed in the ASGPR-positive hepatocarcinoma cell lines HepG2 and Huh7. Mannose-modified polyplexes showed superior cellular uptake and transfection efficacy compared to unmodified and shielded polyplexes in mannose-receptor-expressing dendritic cell-like DC2.4 cells.


Assuntos
Manose , Polietilenoglicóis , Azidas , DNA/metabolismo , Transfecção
20.
Urogynecology (Phila) ; 30(3): 251-255, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38484239

RESUMO

IMPORTANCE: This study is important because it aimed to assess an intervention to decrease patient discomfort after a robotic sacral colpopexy. OBJECTIVE: Our primary outcome was to determine whether preoperative use of polyethylene glycol decreases time to first bowel movement postoperatively. Secondary outcomes include degree of pain with first bowel movement and stool consistency. STUDY DESIGN: This was a randomized controlled trial. The experimental group was assigned polyethylene glycol daily for 7 days before surgery and the control group was not. All patients received polyethylene glycol postoperatively. RESULTS: There was no statistically significant reduction in the time to first postoperative bowel movement when preoperative polyethylene glycol was used (mean [SD] in days for the control and experimental groups of 2.32 [0.99] and 1.96 [1.00], P = 0.21). There was a statistically significant reduction in pain levels with the first postoperative bowel movement in the experimental group (median [IQR] of 4 [2-5] vs 1 [0-2], P = 0.0007). Postoperative day 1 pain levels were also significantly lower in the experimental group (median [IQR] of 4 [3-6] vs 2 [0-4], P = 0.0484). In addition, patients had decreased average postoperative pain levels over 7 days with an estimated difference in the median pain levels of 1.88 units (95% confidence interval, 0.64-3.12; P = 0.0038). CONCLUSIONS: Preoperative administration of polyethylene glycol did not decrease time to first postoperative bowel movement. Patients in the experimental group exhibited less pain with their first postoperative bowel movement and had improved pain levels on postoperative day 1.


Assuntos
Defecação , Polietilenoglicóis , Humanos , Polietilenoglicóis/uso terapêutico , Dor Pós-Operatória
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