Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 4 de 4
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Drug Deliv Transl Res ; 14(7): 1794-1809, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38165530

RESUMO

Mice as a crucial tool for preclinical assessment of antineoplastic agents. The impact of physiological differences among mouse strains on the in vivo efficacy of antitumor drugs, however, has been significantly overlooked. Mononuclear phagocyte system (MPS) is the major player in clearance in vivo, and differences in MPS among different strains may potentially impact the effectiveness of antitumor preparations. Therefore, in this study, we employed conventional liposomes (CL-EPI) and SA-ODA modified liposomes (SAL-EPI) as model preparations to investigate the comprehensive tumor therapeutic effects of CL-EPI and SAL-EPI in KM, BALB/c, and C57BL/6 tumor-bearing mice. The results demonstrated significant variability in the efficacy of CL-EPI for tumor treatment across different mouse strains. Therefore, we should pay attention to the selection of animal models in the study of antitumor agents. SAL-EPI effectively targeted tumor sites by binding to Siglec-1 on the surface of peripheral blood monocytes (PBMs), and achieved good therapeutic effect in different mouse strains with little difference in treatment. The SA modified preparation is therefore expected to achieve a favorable therapeutic effect in tumor patients with different immune states through PBMs delivery (Siglec-1 was expressed in both mice and humans), thereby possessing clinical translational value and promising development prospects.


Assuntos
Antineoplásicos , Lipossomos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Ácido N-Acetilneuramínico/química , Ácido N-Acetilneuramínico/administração & dosagem , Camundongos , Linhagem Celular Tumoral , Lectina 1 Semelhante a Ig de Ligação ao Ácido Siálico , Feminino , Modelos Animais de Doenças , Especificidade da Espécie
2.
ACS Appl Mater Interfaces ; 15(27): 32110-32120, 2023 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-37384837

RESUMO

In recent years, cationic liposomes have been successfully used as delivery platforms for mRNA vaccines. Poly(ethylene glycol) (PEG)-lipid derivatives are widely used to enhance the stability and reduce the toxicity of cationic liposomes. However, these derivatives are often immunogenic, triggering the rise of anti-PEG antibodies. Understanding the role and impact of PEG-lipid derivatives on PEGylated cationic liposomes is key to solving the PEG dilemma. In this study, we designed linear, branched, and cleavable-branched cationic liposomes modified with PEG-lipid derivatives and investigated the effect of the liposome-induced accelerated blood clearance (ABC) phenomenon on photothermal therapy. Our study indicated that the linear PEG-lipid derivatives mediated the effect of photothermal therapy by stimulating splenic marginal zone (MZ) B cells to secrete anti-PEG antibodies and increasing the level of IgM expression in the follicular region of the spleen. However, the cleavable-branched and branched PEG-lipid derivatives did not activate the complement system and avoided the ABC phenomenon by inducing noticeably lower levels of anti-PEG antibodies. The cleavable-branched PEGylated cationic liposomes improved the effect of photothermal therapy by reversing the charge on the liposome surface. This detailed study of PEG-lipid derivatives contributes to the further development and clinical application of PEGylated cationic liposomes.


Assuntos
Lipossomos , Polímeros , Terapia Fototérmica , Imunoglobulina M , Polietilenoglicóis , Lipídeos
3.
Eur J Pharm Biopharm ; 184: 50-61, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36682511

RESUMO

Although anti-tumor strategies targeting tumor-associated immune cells were being rapidly developed, the preparations were usually limited in targeting efficiency. To overcome this barrier, this study reported a novel sialic acid-octadecylamine (SA-ODA) and monosialotetrahexosylganglioside (GM1) co-modified epirubicin liposomes (5-5-SAGL-EPI), which improved tumor-targeting ability through the active targeting of tumor-associated macrophages (TAMs) by SA-ODA and the long circulation of GM1. Thus, we evaluated 5-5-SAGL-EPI in vitro and in vivo. Analysis of cellular uptake by RAW264.7 cells using flow cytometry and confocal microscopy showed a higher rate of cellular uptake for 5-5-SAGL-EPI than for the common liposomes (CL-EPI). In pharmacokinetic studies using Wistar rats, compared to CL-EPI, 5-5-SAGL-EPI showed a higher circulation time in vivo. Tissue distribution studies in Kunming mice bearing S180 tumors revealed increased distribution of 5-5-SAGL-EPI in tumor tissues compared with liposomes modified with single ligands (SA-ODA [5-SAL-EPI] or GM1 [5-GL-EPI]). In vivo anti-tumor experiments using the S180 tumor-bearing mice revealed a high tumor inhibition rate and low toxicity for 5-5-SAGL-EPI. Moreover, freeze-dried 5-5-SAGL-EPI had good storage stability, and the anti-tumor effect was comparable to that before freeze-drying. Overall, 5-5-SAGL-EPI exhibited excellent anti-tumor effects before and after lyophilization.


Assuntos
Lipossomos , Ácido N-Acetilneuramínico , Camundongos , Ratos , Animais , Lipossomos/farmacologia , Ácido N-Acetilneuramínico/farmacologia , Macrófagos Associados a Tumor , Microambiente Tumoral , Gangliosídeo G(M1)/farmacologia , Ratos Wistar , Linhagem Celular Tumoral
4.
Life Sci ; 310: 121081, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36273630

RESUMO

AIMS: Sialic acid derivatives (SA-derivatives) provide a nanomedicine platform for tumor-targeted delivery and treatment, and allow modulation of immunosuppressive tumor microenvironments with excellent therapeutic effects. Further, the multi-reactive groups of sialic acid (SA) contribute to the diversity of SA derivatives, which inevitably has implications for drug delivery systems and tumor therapy. However, relevant research remains lacking at present. Therefore, this study aimed to explore the effects of SA derivatives on SA-mediated drug delivery systems. MAIN METHODS: Four SA-derivatives with different linking bonds (ester and amide bonds), different linking groups (hydroxyl and carboxyl), and different linking objects (cholesterol, octadecanoic acid, and octadecylamine) were synthesized and the respective SA derivative-modified doxorubicin liposomes were prepared. In-depth research was conducted using both cells and animals. KEY FINDINGS: We found that an SA-cholesterol conjugate (SA-CH; linking bond, amide bond; linking group, carboxyl; linking object, cholesterol) could improve liposome stability, reduce liposome adsorption to plasma proteins, and enhance the targeting of liposomes for killing tumor-associated macrophages (TAMs). Reduced TAMs in the immunosuppressive tumor microenvironment lead to enhanced tumor infiltration of CD8+ T cells. SIGNIFICANCE: The results of this experiment provide clarity for research and development on SA-derivatives and a theoretical basis for clinical trials of SA-derivative-modified nanoparticles.


Assuntos
Lipossomos , Neoplasias , Animais , Lipossomos/química , Microambiente Tumoral , Ácido N-Acetilneuramínico/química , Ácido N-Acetilneuramínico/farmacologia , Linfócitos T CD8-Positivos/metabolismo , Neoplasias/tratamento farmacológico , Colesterol/química , Amidas/farmacologia , Linhagem Celular Tumoral
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...