Abstract:
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.
摘要:
鼻咽癌(NPC)是一种常见的头颈部恶性肿瘤,其特点是发病率高,攻击性强,诊断差,治疗机会有限。实现精确的NPC主动靶向药物递送的创新策略已成为临床研究的突出焦点。这里,设计了一种极简主义的癌细胞膜(CCM)屏蔽仿生纳米粒子(NP),用于NPC主动靶向治疗.将化学疗法模型药物阿霉素(DOX)装载在聚酰胺胺(PAMAM)树枝状聚合物中。PAMAM/DOX(PD)NP进一步被人CNE-2NPCCCM屏蔽。表征结果表明,仿生PAMAM/DOX@CCM(简称PDC)NPs具有令人满意的物理特性,具有高DOX负载和出色的稳定性。细胞实验表明,CNE-2膜遮盖的PDCNP通过同源靶向和粘附相互作用在来源细胞中呈现强大的细胞摄取。进一步的体内结果证实,这种仿生纳米平台具有延长的循环和显着的肿瘤靶向能力,和PDCNP通过全身给药有效抑制CNE-2肿瘤的进展。这种CCM屏蔽的仿生NP展示了一种用于精确NPC治疗的极简范式纳米平台,CCM屏蔽仿生药物递送系统(DDS)的策略在广泛的癌症主动靶向治疗中具有巨大的潜力。