Abstract

As a new type of cancer treatment, photoacoustic (PA) therapy is based on PA shockwave for rapid, selective and effective killing of cancer cells. The nucleus has been widely used as a target for tumor therapy, which has obtained a very considerable therapeutic effect. In situ destruction of tumor cell nucleus by photoacoustic therapy has not been studied. In this paper, a highly efficient nucleus-targeted photoacoustic theranostic polymer was developed for fluorescence and photoacoustic dual-mode imaging-guided PA therapy. The prepared polymer consists of nucleus targeting TAT peptide (TAT: YGRKKRRQRRR), hydrophilic chain poly (N,N-dimethylacrylamide) (PDMA), and near-infrared (NIR) light absorbing agent (hCyR), which can self-assemble to form nanoparticles of approximately 28 nm (denoted as TAT-PDMA-hCyR NPs). The designed nanoparticles show excellent nucleus targeting and tumor cell death (up to 80%) caused by DNA damage under pulsed laser irradiation compared to non-nucleus target counterpart PDMA-hCyR NPs without TAT peptide in vitro. As expected, the fluorescence and PA dual-mode imaging observed that TAT-PDMA-hCyR NPs were able to passively target and enrich in tumors, providing an experimental basis for in vivo treatment and thus ensuring a significant tumor inhibition rate (about 92%). In conclusion, this study provides a new and practicable method for the development of nucleus-targeting nanoparticles as potential theranostic agent for in vivo cancer imaging and therapy.

中文翻译：

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通过核靶向纳米粒子进行的特定光声空化，可用于高效肿瘤治疗

摘要

作为一种新型的癌症治疗方法，光声（PA）治疗基于PA冲击波，可以快速，选择性和有效地杀死癌细胞。细胞核已被广泛用作肿瘤治​​疗的靶标，已经获得了非常可观的治疗效果。原位尚未研究通过光声疗法破坏肿瘤细胞核。在本文中，开发了一种高效的针对核的光声治疗药物，用于荧光和光声双模成像引导的PA治疗。制备的聚合物由靶向TAT肽的原子核（TAT：YGRKKRRQRRR），亲水链聚（N，N-二甲基丙烯酰胺）（PDMA）和近红外（NIR）光吸收剂（hCyR）组成，它们可以自组装形成约28 nm的纳米颗粒（表示为TAT-PDMA-hCyR NPs）。与无TAT肽的无核靶标PDMA-hCyR NPs相比，在脉冲激光照射下，设计的纳米颗粒显示出出色的核靶向和由脉冲激光照射下DNA损伤引起的肿瘤细胞死亡（高达80％）。。如预期的那样，荧光和PA双模成像观察到TAT-PDMA-hCyR NP能够被动靶向并富集肿瘤，为体内治疗提供了实验基础，从而确保了显着的肿瘤抑制率（约92％） 。总而言之，这项研究为开发针对核的纳米粒子作为体内癌症成像和治疗的潜在治疗方法提供了一种新的实用方法。