DOX/IL-2/IFN-γ co-loaded thermo-sensitive polypeptide hydrogel for efficient melanoma treatment

Melanoma has been a serious threat to the human health; however, effective therapeutic methods of this cancer are still limited. Combined local therapy is a crucial approach for achieving a superior anti-tumor efficacy. In this paper, a chemo-immunotherapy system of DOX, IL-2 and IFN-γ based on poly...

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Main Authors: Qiang Lv, Chaoliang He, Fenli Quan, Shuangjiang Yu, Xuesi Chen
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2018-03-01
Series:Bioactive Materials
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X17300774
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author Qiang Lv
Chaoliang He
Fenli Quan
Shuangjiang Yu
Xuesi Chen
author_facet Qiang Lv
Chaoliang He
Fenli Quan
Shuangjiang Yu
Xuesi Chen
author_sort Qiang Lv
collection DOAJ
description Melanoma has been a serious threat to the human health; however, effective therapeutic methods of this cancer are still limited. Combined local therapy is a crucial approach for achieving a superior anti-tumor efficacy. In this paper, a chemo-immunotherapy system of DOX, IL-2 and IFN-γ based on poly(γ-ethyl-L-glutamate)-poly(ethylene glycol)-poly(γ-ethyl-L-glutamate) (PELG-PEG-PELG) hydrogel was developed for local treatment of melanoma xenograft. The drug release process of this system exhibited a short term of burst release (the first 3 days), followed by a long-term sustained release (the following 26 days). The hydrogel degraded completely within 3 weeks without obvious inflammatory responses in the subcutaneous layer of rats, showing a good biodegradability and biocompatibility. The DOX/IL-2/IFN-γ co-loaded hydrogel also showed enhanced anti-tumor effect against B16F10 cells in vitro, through increasing the ratio of cell apoptosis and G2/S phage cycle arrest. Moreover, the combined strategy presented improved therapy efficacy against B16F10 melanoma xenograft without obvious systemic side effects in a nude mice model, which was likely related to both the enhanced tumor cell apoptosis and the increased proliferation of the CD3+/CD4+ T-lymphocytes and CD3+/CD8+ T-lymphocytes. Overall, the strategy of localized co-delivery of DOX/IL-2/IFN-γ using the polypeptide hydrogel provided a promising approach for efficient melanoma therapy.
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spelling doaj.art-7ad9279a3f2f4257a1ab988e70c600c62024-04-16T22:12:06ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2018-03-013111812810.1016/j.bioactmat.2017.08.003DOX/IL-2/IFN-γ co-loaded thermo-sensitive polypeptide hydrogel for efficient melanoma treatmentQiang Lv0Chaoliang He1Fenli Quan2Shuangjiang Yu3Xuesi Chen4Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, 130021, ChinaKey Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, ChinaKey Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, ChinaKey Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, ChinaKey Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, ChinaMelanoma has been a serious threat to the human health; however, effective therapeutic methods of this cancer are still limited. Combined local therapy is a crucial approach for achieving a superior anti-tumor efficacy. In this paper, a chemo-immunotherapy system of DOX, IL-2 and IFN-γ based on poly(γ-ethyl-L-glutamate)-poly(ethylene glycol)-poly(γ-ethyl-L-glutamate) (PELG-PEG-PELG) hydrogel was developed for local treatment of melanoma xenograft. The drug release process of this system exhibited a short term of burst release (the first 3 days), followed by a long-term sustained release (the following 26 days). The hydrogel degraded completely within 3 weeks without obvious inflammatory responses in the subcutaneous layer of rats, showing a good biodegradability and biocompatibility. The DOX/IL-2/IFN-γ co-loaded hydrogel also showed enhanced anti-tumor effect against B16F10 cells in vitro, through increasing the ratio of cell apoptosis and G2/S phage cycle arrest. Moreover, the combined strategy presented improved therapy efficacy against B16F10 melanoma xenograft without obvious systemic side effects in a nude mice model, which was likely related to both the enhanced tumor cell apoptosis and the increased proliferation of the CD3+/CD4+ T-lymphocytes and CD3+/CD8+ T-lymphocytes. Overall, the strategy of localized co-delivery of DOX/IL-2/IFN-γ using the polypeptide hydrogel provided a promising approach for efficient melanoma therapy.http://www.sciencedirect.com/science/article/pii/S2452199X17300774Polypeptide hydrogelSustained co-deliveryCombination therapyLocal cancer treatmentThermosensitive hydrogel
spellingShingle Qiang Lv
Chaoliang He
Fenli Quan
Shuangjiang Yu
Xuesi Chen
DOX/IL-2/IFN-γ co-loaded thermo-sensitive polypeptide hydrogel for efficient melanoma treatment
Bioactive Materials
Polypeptide hydrogel
Sustained co-delivery
Combination therapy
Local cancer treatment
Thermosensitive hydrogel
title DOX/IL-2/IFN-γ co-loaded thermo-sensitive polypeptide hydrogel for efficient melanoma treatment
title_full DOX/IL-2/IFN-γ co-loaded thermo-sensitive polypeptide hydrogel for efficient melanoma treatment
title_fullStr DOX/IL-2/IFN-γ co-loaded thermo-sensitive polypeptide hydrogel for efficient melanoma treatment
title_full_unstemmed DOX/IL-2/IFN-γ co-loaded thermo-sensitive polypeptide hydrogel for efficient melanoma treatment
title_short DOX/IL-2/IFN-γ co-loaded thermo-sensitive polypeptide hydrogel for efficient melanoma treatment
title_sort dox il 2 ifn γ co loaded thermo sensitive polypeptide hydrogel for efficient melanoma treatment
topic Polypeptide hydrogel
Sustained co-delivery
Combination therapy
Local cancer treatment
Thermosensitive hydrogel
url http://www.sciencedirect.com/science/article/pii/S2452199X17300774
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