Cancer-Cell-Membrane-Coated Nanoparticles with a Yolk-Shell Structure Augment Cancer Chemotherapy
Cancer-Cell-Membrane-Coated Nanoparticles with a Yolk-Shell Structure Augment Cancer Chemotherapy
复制标题
具有卵黄壳结构的癌细胞膜涂层纳米粒子增强癌症化疗。
DOI：
10.1021/acs.nanolett.9b03817
复制
发表时间：
2020-02-01
期刊：
影响因子：
10.8
通讯作者：
Gan, Yong
中科院分区：
文献类型：
--
作者：
Nie, Di;Dai, Zhuo;Gan, Yong
尽管抗肿瘤药物递送技术发展迅速，但细胞内转运不足和亚细胞药物蓄积仍是有待解决的问题。癌细胞膜包裹的纳米颗粒由于具有免疫逃逸和同型结合能力，在肿瘤治疗中显示出很好的潜力。然而，由于肿瘤穿透效率低和细胞内转运受损，它们的功效仍然有限。本文中，开发了具有介孔二氧化硅纳米颗粒（MSN）支撑的PEG化脂质体蛋黄和CCM涂层的蛋黄-壳NP，CCM@LM，用于化疗，并表现出同源肿瘤靶向作用。卵黄-壳结构赋予CCM@LM适度的刚性，这可能有助于在浸润过程中频繁转化为椭圆形，从而促进体外渗透穿过多细胞球体（与膜囊泡的渗透相比，增加高达23.3倍）。CCM@LM还表现出模仿包膜病毒侵袭谱的细胞侵袭谱。CCM@LM通过膜融合直接内化，并且聚乙二醇化的卵黄（LM）随后释放到胞质溶胶中，表明执行类似于包膜病毒的内化途径。进入的PEG化LM进一步在整个细胞骨架细丝网络中进行有效运输，导致增强的核周聚集。最终，CCM@LM共包封低剂量阿霉素和聚（ADP-核糖）聚合酶抑制剂盐酸美夫帕尼，表现出比一线化疗药物Doxil显著更强的抗肿瘤作用。我们的研究结果强调，可以进行促进肿瘤渗透和强大的细胞内运输的纳米粒子在癌症化疗中有着光明的未来。
Despite rapid advancements in antitumor drug delivery, insufficient intracellular transport and subcellular drug accumulation are still issues to be addressed. Cancer cell membrane (CCM)-camouflaged nanoparticles (NPs) have shown promising potential in tumor therapy due to their immune escape and homotypic binding capacities. However, their efficacy is still limited due to inefficient tumor penetration and compromised intracellular transportation. Herein, a yolk-shell NP with a mesoporous silica nanoparticle (MSN)supported PEGylated liposome yolk and CCM coating, CCM@LM, was developed for chemotherapy and exhibited a homologous tumor-targeting effect. The yolk-shell structure endowed CCM@LM with moderate rigidity, which might contribute to the frequent transformation into an ellipsoidal shape during infiltration, leading to facilitated penetration throughout multicellular spheroids in vitro (up to a 23.3-fold increase compared to the penetration of membrane vesicles). CCM@LM also exhibited a cellular invasion profile mimicking an enveloped virus invasion profile. CCM@LM was directly internalized by membrane fusion, and the PEGylated yolk (LM) was subsequently released into the cytosol, indicating the execution of an internalization pathway similar to that of an enveloped virus. The incoming PEGylated LM further underwent efficient trafficking throughout the cytoskeletal filament network, leading to enhanced perinuclear aggregation. Ultimately, CCM@LM, which co-encapsulated low-dose doxorubicin and the poly(ADP-ribose) polymerase inhibitor, mefuparib hydrochloride, exhibited a significantly stronger antitumor effect than the first-line chemotherapeutic drug Doxil. Our findings highlight that NPs that can undergo facilitated tumor penetration and robust intracellular trafficking have a promising future in cancer chemotherapy.