Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 300044, Taiwan.
Nano Lett. 2021 Feb 10;21(3):1375-1383. doi: 10.1021/acs.nanolett.0c04122. Epub 2020 Dec 2.
T lymphocytes infiltrate the most devastating metastatic tumors for immunotherapy, allowing the potential for tumor metastasis suppression. However, tumor heterogeneity often restricts the infiltration of immune cells and possesses immune privilege that leads to protection from the immune attack, especially for invading metastatic clusters. Here, an exosome-camouflaged nanoraspberry (RB@Exo) doubling as a metastases-targeting agent and T cell-infiltration inducer that delivers an anticancer drug and energy is reported. The RB@Exo integrated an exosome-derived margination effect, and density-mediated nanoparticle-induced extracellular leakiness (nanoEL) exhibited more than a 70% colocalization of the RB@Exo to metastatic tumors in the lung . The release of cancer cell-cell interactions at the metastasis via nanoEL also elicited the 10-fold infiltration of T lymphocytes. The synergy of the T cell infiltration and photolytic effects transported by the RB@Exo deep into the metastatic tumors effectively inhibited the tumor in 60 days when treated with a single alternating magnetic field (AMF).
T 淋巴细胞浸润免疫疗法最具破坏性的转移性肿瘤，从而有可能抑制肿瘤转移。然而，肿瘤异质性常常限制免疫细胞的浸润，并具有免疫特权，使其免受免疫攻击，尤其是对于侵袭性转移性簇。在这里，报告了一种外泌体伪装纳米红莓（RB@Exo），它兼具转移性靶向剂和 T 细胞浸润诱导剂的双重功能，可递送抗癌药物和能量。RB@Exo 整合了外泌体衍生的靠边效应，以及密度介导的纳米颗粒诱导的细胞外通透性（nanoEL），使 RB@Exo 与肺部转移性肿瘤的超过 70%的共定位。通过 nanoEL 释放转移过程中的癌细胞-细胞相互作用，也引发了 T 淋巴细胞的 10 倍浸润。RB@Exo 运输的 T 细胞浸润和光解效应的协同作用，在 60 天的单一交变磁场（AMF）治疗后，可有效抑制肿瘤。
