Biodegradable Nanocomposite with Dual Cell-Tissue Penetration for Deep Tumor Chemo-Phototherapy
Biodegradable Nanocomposite with Dual Cell-Tissue Penetration for Deep Tumor Chemo-Phototherapy
复制标题
具有双细胞组织渗透性的可生物降解纳米复合材料用于深层肿瘤化疗光疗
DOI：
10.1002/smll.202000809
复制
发表时间：
2020-05-06
期刊：
影响因子：
13.3
通讯作者：
Liu, Huiyu
中科院分区：
文献类型：
--
作者：
Pan, Xueting;Li, Pengju;Liu, Huiyu
光化学疗法作为一种很有前途的肿瘤综合治疗策略，已引起广泛关注。然而，复杂的肿瘤微环境限制了化疗药物在肿瘤区域的渗透深度。在这里，可生物降解的两亲性明胶（AG）包裹的纳米复合材料（PRDCuS@AG）组成的阿霉素和硫化铜（CuS）负载的树枝状聚合物被设计用于深部肿瘤化疗-光疗。PRDCuS@AG中的PR表示甘氨酸缀合的聚酰胺胺树状聚合物。PRDCuS@AG在近红外光照射下可被基质金属蛋白酶快速降解为PRDCuS。所得到的PRDCuS具有双重细胞-组织穿透能力，其可以有效地穿透到肿瘤组织深处。特别是PRDCuS@AG实现了光声成像引导的协同化疗-光疗，肿瘤抑制率达97%。此外，PRDCuS@AG可以进一步降解为3 nm的超小CuS，治疗后可以从体内消除，以避免副作用。这一策略为开发具有高穿透能力的化学-光疗剂以克服当前肿瘤深部治疗的局限性提供了启示。
Chemo-phototherapy, as a promising cancer combination therapy strategy, has attracted widespread attention. However, the complex tumor microenvironment restricts the penetration depth of chemo-phototherapy agents in the tumor region. Here, biodegradable amphiphilic gelatin (AG) wrapped nanocomposite (PRDCuS@AG) composed of doxorubicin and copper sulfide (CuS)-loaded dendrimer is designed for deep tumor chemo-phototherapy. PR in PRDCuS@AG represents arginine-conjugated polyamidoamine dendrimer. PRDCuS@AG can rapidly biodegrade into PRDCuS by matrix metalloproteinases under near-infrared light irradiation. The resulted PRDCuS harbors dual cell-tissue penetration ability, which can effectively penetrate deep into the tumor tissue. In particular, PRDCuS@AG achieves photoacoustic imaging-guided synergistic chemo-phototherapy with 97% of tumor inhibition rate. Moreover, PRDCuS@AG can further degrade into 3 nm ultrasmall CuS, which can be eliminated from the body after treatment to avoid side effects. This strategy provides an insight that the development of chemo-phototherapy agents with high penetration ability to overcome the limitation of current deep tumor therapy.