肿瘤酸度驱动的纳米马达可以为肿瘤特异性穿透药物输送提供强大的推进力。在此，设计了一种酸度驱动的聚（氨基酸）磷酸钙（CaP）混合纳米电机（PCaPmotor），使用mPEG-PAsp-PPhe@THZ531胶束（Poly@THZ）进行CaP矿化，并封装αPD-L1抗体。 CaP 层在酸性肿瘤环境中溶解，释放出热能，推动纳米马达增强细胞摄取和渗透到深层癌细胞，同时促进 αPD-L1 释放。 PCaPmotor 传递的 THZ531 抑制 CDK12 及其下游 RNAP-II 磷酸化，从而增加癌症免疫原性事件，如 DNA 损伤、细胞凋亡、免疫原性细胞死亡、溶酶体功能紊乱和 MHC-I 上调。 PCaPmotor 共同提供的 THZ531 和 αPD-L1 显着增加了 DC 成熟和 CTL 瘤内浸润的频率，但两种游离药物则没有。因此，PCaP@THZ/αPD-L1 纳米电机在小鼠体内产生了协同抗癌免疫疗法。这种酸驱动的 PCaP 马达代表了穿透药物输送的新范例。

Tumor acidity-driven nanomotors may offer robust propulsion for tumor-specific penetrating drug delivery. Herein, an acidity-actuated poly(amino acid) calcium phosphate (CaP) hybrid nanomotor (PCaPmotor) was designed, using a mPEG-PAsp-PPhe@THZ531 micelle (Poly@THZ) for CaP mineralization accompanied by αPD-L1 antibody encapsulation. Dissolution of the CaP layer in an acidic tumor environment gave off heat energy to propel the nanomotor to augment the cellular uptake and penetration into deeply seated cancer cells while facilitating αPD-L1 release. THZ531 delivered by the PCaPmotor inhibited CDK12 and its down-streamed phosphorylation of RNAP-II to increase the cancer immunogenicity events such as the DNA damage, cell apoptosis, immunogenic cell death, lysosomal function disturbance, and MHC-I upregulation. THZ531 and αPD-L1 cosupplied by PCaPmotor significantly increased the frequency of DCs maturation and intratumoral infiltration of CTLs, but the two free drugs did not. Consequently, the PCaP@THZ/αPD-L1 nanomotor resulted in synergistic anticancer immunotherapy in mice. This acid-actuated PCaPmotor represented a new paradigm for penetrating drug delivery.