Enhanced anti-tumor efficacy of hyaluronic acid modified nanocomposites combined with sonochemotherapy against subcutaneous and metastatic breast tumors
Enhanced anti-tumor efficacy of hyaluronic acid modified nanocomposites combined with sonochemotherapy against subcutaneous and metastatic breast tumors
复制标题
透明质酸修饰纳米复合材料联合声化疗增强对皮下和转移性乳腺肿瘤的抗肿瘤功效
DOI：
10.1039/c9nr01691k
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发表时间：
2019
期刊：
影响因子：
6.7
通讯作者：
Zong Yujin
中科院分区：
文献类型：
--
作者：
Wu Pengying;Sun Yue;Dong Wei;Zhou Huige;Guo Shifang;Zhang Lei;Wang Xiaobing;Wan Mingxi;Zong Yujin
超声化疗是一种很有前途的抑制肿瘤生长的策略。然而，实现高靶向性和有效的声化疗仍然是一个巨大的挑战。在这项研究中，开发了一种新型的携带化疗药物的纳米复合材料（HPCID），它可以有效地靶向转移性癌细胞并提供增强的治疗效果。具体地，HPCID由透明质酸（HA）、羧基封端的PAMAM树状聚合物、荧光染料吲哚菁绿色（ICG）和盐酸阿霉素（Dox）组成。该药物递送系统（DDS）在超声化疗中的疗效进行了评估，在CD44过表达转移性乳腺癌细胞系4T1在体外和体内。HA修饰显著改善了HPCID的细胞内化，并且4T1细胞中丰富的透明质酸酶对HA壳的降解导致酶响应性药物释放。在超声（US）刺激下，HPCID产生大量的活性氧化剂（ROS），当与化疗联合时，其诱导显著的细胞凋亡。此外，在4T1异种移植荷瘤小鼠中施用HPCID结合超声照射显著抑制肿瘤生长和肺转移，而没有全身毒性。总之，提出的HPCID介导的声动力学治疗（SDT）是一种新的策略，对乳腺癌的进展和转移。
Sonochemotherapy is a promising strategy for inhibiting tumor growth. However, achieving highly targeted and effective sonochemotherapy is still an enormous challenge. In this study, a novel chemotherapeutic-carrying nanocomposite (HPCID) was developed, which can effectively target metastatic cancer cells and provide an enhanced therapeutic effect. In detail, HPCID was composed of hyaluronic acid (HA), carboxyl-terminated PAMAM dendrimer, fluorochrome indocyanine green (ICG), and doxorubicin hydrochloride (Dox). The efficacy of this drug delivery system (DDS) in sonochemotherapy was assessed on the CD44-overexpressing metastatic breast cancer cell line 4T1 both in vitro and in vivo. The HA modification significantly improved the cellular internalization of HPCID, and the degradation of the HA shell by hyaluronidase that is abundant in the 4T1 cells resulted in enzyme-responsive drug release. Under ultrasound (US) stimulation, HPCID produced a high amount of reactive oxidant species (ROS), which induced significant cell apoptosis when combined with chemotherapy. In addition, the administration of HPCID in 4T1 xenograft-bearing mice combined with ultrasonic exposure significantly inhibited tumor growth and pulmonary metastasis, with no systemic toxicity. Taken together, the proposed HPCID-mediated sonodynamic therapy (SDT) is a novel strategy against breast cancer progression and metastasis.