State Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.
State Key Laboratory of Agricultural Microbiology, College of Science, Huazhong Agricultural University, Wuhan 430070, China.
ACS Appl Mater Interfaces. 2020 Sep 2;12(35):39434-39443. doi: 10.1021/acsami.0c11469. Epub 2020 Aug 18.
Photothermal therapy (PTT) is considered an alternative for oncotherapy because it has less invasive damage to normal tissues than other methods, particularly in second near-infrared (NIR-II) PTT (1000-1350 nm) because of deeper biological tissue penetration, lower photon scattering, and higher maximum permissible exposure (1.0 W cm). However, for achieving a higher therapeutic effect, the delivery of large amounts of NIR-sensitive agents has been pursued, which in turn enormously increases damage to normal cells. Herein, we developed peptide-coated platinum nanoparticles (TPP-Pt) to create violent damage for a given amount of hyperthermia by purposefully delivering TPP-Pt to the thermally susceptible mitochondria with minimal side effects. Mitochondrial peptide targeting endowed ultrasmall platinum nanoparticles (PtNPs) with monodispersity, high stability, biosafety, and enhanced uptake of cancer cells and priority of mitochondria, causing efficient PTT. Moreover, an experiment showed that the excellent tumor inhibitory effect and negligible side effects could be achieved with the preferentially striking thermosensitive mitochondria strategy. The mitochondria-based "win by one move" therapeutic platform of peptide-coated platinum nanoparticles (TPP-Pt) demonstrated here will find great potential to overcome the challenges of low therapeutic efficiency and strong systemic side effects in PTT.
光热疗法（PTT）被认为是肿瘤治疗的一种替代方法，因为它对正常组织的侵入性损伤比其他方法小，特别是在第二个近红外（NIR-II）PTT（1000-1350nm）中，因为它具有更深的生物组织穿透性、更低的光子散射和更高的最大允许暴露量（1.0W/cm）。然而，为了达到更高的治疗效果，人们一直在追求大量的近红外敏感剂的输送，这反过来又极大地增加了正常细胞的损伤。在这里，我们开发了肽涂层的铂纳米粒子（TPP-Pt），通过有针对性地将 TPP-Pt 递送到对热敏感的线粒体来产生剧烈的损伤，从而在给定的热疗下实现更高的治疗效果，同时最小化副作用。线粒体肽靶向赋予了超小铂纳米粒子（PtNPs）单分散性、高稳定性、生物安全性和增强的癌细胞摄取和优先摄取线粒体的能力，从而实现了高效的 PTT。此外，实验表明，采用优先靶向热敏线粒体的策略，可以达到优异的肿瘤抑制效果和可忽略的副作用。这里展示的基于线粒体的“一步制胜”肽涂层铂纳米粒子（TPP-Pt）治疗平台将有很大的潜力克服 PTT 中治疗效率低和全身副作用强的挑战。
