RESUMEN
Paclitaxel (PTX) is a first-line drug for the treatment of lung cancer, but its targeting and therapeutic effect are unsatisfactory. Herein, lung cancer cell (A549) membrane biomimetic PTX-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (AM@PTX-NPs) were constructed to eliminate the shortcomings of PTX. The AM@PTX-NPs were successfully prepared with a high drug loading efficiency (10.90±0.06â¯%). Moreover, transmission electron microscopy, SDS-PAGE, and western blotting proved that AM@PTX-NPs were spherical nanoparticles camouflaged by the A549 cell membrane. Both in vitro and in vivo assays revealed that the AM@PTX-NPs displayed outstanding targeting capacity due to A549 membrane modification. The cytotoxicity experiment showed that the developed biomimetic formulation was able to effectively reduce the proliferation of A549 cells. Moreover, AM@PTX-NPs exhibited a significant tumor growth inhibition rate (73.00â¯%) with good safety in the tumor-bearing mice, which was higher than that of the PTX-NPs without A549 membrane coating (37.39â¯%). Overall, the constructed bioinspired vector could provide a novel platform for the PTX delivery and demonstrated a promising strategy for the targeted cancer treatment.
Asunto(s)
Membrana Celular , Neoplasias Pulmonares , Nanopartículas , Paclitaxel , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Paclitaxel/farmacología , Paclitaxel/administración & dosificación , Paclitaxel/química , Humanos , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Animales , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Células A549 , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Nanopartículas/química , Ratones , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/química , Ratones Desnudos , Ratones Endogámicos BALB C , Ensayos Antitumor por Modelo de Xenoinjerto , Portadores de Fármacos/químicaRESUMEN
Curcumin (CUR) is a promising natural product for hepatocellular carcinoma (HCC) therapy. However, its clinical application has been limited by some issues such as rapid clearance and inadequate tumor accumulation. To address these drawbacks, we developed platelet membrane-coated CUR-loaded PLGA nanoparticles (PCPNPs). In this work, due to the bioinspired strategy, the PCPNPs exhibited immune evasion, prolonged circulation, and improved accumulation at tumor sites compared to the traditional CUR formulation. The superior tumor targeting of PCPNPs was likely due to the interactions between platelet P-selectin and tumoral CD44. Furthermore, both in vitro and in vivo assays revealed that the PCPNPs showed outstanding anticancer efficacy without obvious toxicity. Therefore, PCPNPs represent a biosafe and promising anti-tumor strategy, overcoming the limitations associated with CUR. These findings not only contribute to the advancement of natural compound nano-formulation but also open new avenues for targeted cancer treatment.
Asunto(s)
Carcinoma Hepatocelular , Curcumina , Neoplasias Hepáticas , Nanopartículas , Nanopartículas/química , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Animales , Humanos , Curcumina/química , Curcumina/farmacología , Ratones , Plaquetas/efectos de los fármacos , Plaquetas/metabolismo , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Antineoplásicos/farmacología , Antineoplásicos/química , Ratones Endogámicos BALB C , Proliferación Celular/efectos de los fármacos , Tamaño de la Partícula , Ratones Desnudos , Línea Celular TumoralRESUMEN
Synthetic nanoparticles with surface bioconjugation are promising platforms for targeted therapy, but their simple biological functionalization is still a challenging task against the complex intercellular environment. Once synthetic nanoparticles enter the body, they are phagocytosed by immune cells by the immune system. Recently, the cell membrane camouflage strategy has emerged as a novel therapeutic tactic to overcome these issues by utilizing the fundamental properties of natural cells. Macrophage, a type of immune system cells, plays critical roles in various diseases, including cancer, atherosclerosis, rheumatoid arthritis, infection and inflammation, due to the recognition and engulfment function of removing substances and pathogens. Macrophage membranes inherit the surface protein profiles and biointerfacing properties of source cells. Therefore, the macrophage membrane cloaking can protect synthetic nanoparticles from phagocytosis by the immune cells. Meanwhile, the macrophage membrane can make use of the natural correspondence to accurately recognize antigens and target inflamed tissue or tumor sites. In this review, we have summarized the advances in the fabrication, characterization and homing capacity of macrophage membrane cloaking nanoparticles in various diseases, including cancers, immune diseases, cardiovascular diseases, central nervous system diseases, and microbial infections. Although macrophage membrane-camouflaged nanoparticles are currently in the fetal stage of development, there is huge potential and challenge to explore the conversion mode in the clinic.