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01-12-2019 | Lung Cancer | PRECLINICAL STUDIES

Synergistic effect and reduced toxicity by intratumoral injection of cytarabine-loaded hyaluronic acid hydrogel conjugates combined with radiotherapy on lung cancer

Authors: Juan Tang, Na Wang, JingBo Wu, PeiRong Ren, JunYang Li, LiShi Yang, XiangXiang Shi, Yue Chen, ShaoZhi Fu, Sheng Lin

Published in: Investigational New Drugs | Issue 6/2019

Summary

The aim of this study was to explore the synergistic anti-tumor effects of cytarabine hyaluronic acid-tyramine (Ara-HA-Tyr) hydrogel conjugates and radiotherapy (RT) in the Lewis lung cancer (LLC) xenograft model, and the mechanisms involved. The radiotherapy sensitization ratio (SER) of 0.5 μg cytarabine (Ara-C) was 1.619 in the LLC cells. Ara-HA-Tyr was prepared by encapsulating Ara-C into hyaluronic acid-tyramine (HA-Tyr) conjugates. The hydrogels were formed through the oxidative coupling of tyramines by hydrogen peroxide (H₂O₂) and horseradish peroxidase (HRP). Mice engrafted with the LLC cells were given intra-tumoral injections of saline, Ara-C or Ara-HA-Tyr, with or without RT. The combination of Ara-HA-Tyr and RT increased survival compared to free Ara-C and RT (p < 0.05), and prolonged tumor growth delay (TGD). Furthermore, the RT + Ara-HA-Tyr combination therapy significantly reduced ¹⁸F-FDG uptake, induced cell cycle arrest at G2/M-phase, increased apoptosis and histone H2AX phosphorylation (γ-H2AX), and decreased the proliferation index (Ki67) in tumor cells compared to either monotherapy. Taken together, Ara-C encapsulated with HA-Tyr effectively sensitized tumor xenografts to RT and showed significantly less systemic toxicity.

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Title: Synergistic effect and reduced toxicity by intratumoral injection of cytarabine-loaded hyaluronic acid hydrogel conjugates combined with radiotherapy on lung cancer
Authors: Juan Tang
Na Wang
JingBo Wu
PeiRong Ren
JunYang Li
LiShi Yang
XiangXiang Shi
Yue Chen
ShaoZhi Fu
Sheng Lin
Publication date: 01-12-2019
Publisher: Springer US
Keywords: Lung Cancer
Lung Cancer
Radiotherapy
Lung Cancer
Published in: Investigational New Drugs / Issue 6/2019
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI: https://doi.org/10.1007/s10637-019-00740-4

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