RESUMEN
Nasopharyngeal carcinoma (NPC) is a common head and neck malignancy, which is characterized by high incidence and aggression with poor diagnosis and limited therapeutic opportunity. The innovative strategy for achieving precise NPC active-targeting drug delivery has emerged as a prominent focus in clinical research. Here, a minimalist cancer cell membrane (CCM) shielded biomimetic nanoparticle (NP) was designed for NPC active-targeting therapy. Chemotherapeutant model drug doxorubicin (DOX) was loaded in polyamidoamine (PAMAM) dendrimer. The PAMAM/DOX (PD) NP was further shielded by human CNE-2 NPC CCM. Characterization results verified that the biomimetic PAMAM/DOX@CCM (abbreviated as PDC) NPs had satisfactory physical properties with high DOX-loading and excellent stability. Cell experiments demonstrated that the CNE-2 membrane-cloaked PDC NPs presented powerful cellular uptake in the sourcing cells by homologous targeting and adhesive interaction. Further in vivo results confirmed that this biomimetic nanoplatform had extended circulation and remarkable tumor-targeting capability, and the PDC NPs effectively suppressed the progression of CNE-2 tumors by systemic administration. This CCM-shielded biomimetic NP displayed a minimalist paradigm nanoplatform for precise NPC therapy, and the strategy of CCM-shielded biomimetic drug delivery system (DDS) has great potential for extensive cancer active-targeting therapy.
Asunto(s)
Materiales Biomiméticos , Membrana Celular , Doxorrubicina , Nanopartículas , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Doxorrubicina/farmacología , Doxorrubicina/química , Nanopartículas/química , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/patología , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Membrana Celular/química , Membrana Celular/metabolismo , Membrana Celular/efectos de los fármacos , Animales , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/patología , Dendrímeros/química , Ratones , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos , Antibióticos Antineoplásicos/farmacología , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/administración & dosificación , Proliferación Celular/efectos de los fármacos , Ratones Desnudos , Ratones Endogámicos BALB C , Biomimética , Tamaño de la PartículaRESUMEN
N-Acetylneuraminic acid (Neu5Ac), one of the abundant types of sialic acid, is an emerging anticancer agent owing to its ability to target selectins in the plasma membrane of cancer cells. Considering the functionality of Neu5Ac, obtaining novel Neu5Ac-conjugated materials with a selective and an enhanced antitumor activity has remained a challenge. Herein, we report the supramolecular materials of three novel amphiphiles composed of Neu5Ac as a hydrophilic segment and pyrene or adamantane as a hydrophobic segment. The synthetic amphiphiles 1, 2, and 3 self-assembled into ribbons, vesicles, and irregular aggregates in an aqueous solution, respectively. Among the materials, vesicles of amphiphile 2 showed the most substantial selectivity toward cancer cells, followed by cell death due to the production of reactive oxygen species by the pyrene group. The dual advantage of Neu5Ac-selectivity and the pyrene-cytotoxicity of vesicles of amphiphile 2 can provide a strategy for effective anticancer materials.