Enhanced anti-tumor efficacy of hyaluronic acid modified nanocomposites combined with sonochemotherapy against subcutaneous and metastatic breast tumors

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...

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Bibliographic Details
Published in:Nanoscale 2019-06, Vol.11 (24), p.1147-11483
Main Authors: Wu, Pengying, Sun, Yue, Dong, Wei, Zhou, Huige, Guo, Shifang, Zhang, Lei, Wang, Xiaobing, Wan, Mingxi, Zong, Yujin
Format: Article
Language:English
Subjects:
Animals
Anticancer properties
Apoptosis
Biocompatibility
Breast cancer
Chemotherapy
Doxorubicin
Doxorubicin - chemistry
Doxorubicin - pharmacology
Drug Delivery Systems
Female
Hyaluronic acid
Hyaluronic Acid - chemistry
Hyaluronic Acid - pharmacology
Mammary Neoplasms, Experimental - metabolism
Mammary Neoplasms, Experimental - therapy
Metastasis
Mice
Mice, Inbred BALB C
Nanocomposites
Nanocomposites - chemistry
Nanocomposites - therapeutic use
Neoplasm Metastasis
Toxicity
Tumors
Ultrasonic Therapy
Xenotransplantation
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Summary: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. Schematic illustration of sonochemotherapy using HA-modified nanocomposites.
ISSN:2040-3364
2040-3372
DOI:10.1039/c9nr01691k