Anti-EGFR-iRGD recombinant protein modified biomimetic nanoparticles loaded with gambogic acid to enhance targeting and antitumor ability in colorectal cancer treatment

Zhen Zhang,1,2 Hanqing Qian,1 Jie Huang,1 Huizi Sha,1 Hang Zhang,1 Lixia Yu,1 Baorui Liu,1 Dong Hua,3 Xiaoping Qian1 1Comprehensive Cancer Center, Nanjing Drum Tower Hospital, Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Int...

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Autores principales:	Zhang Z, Qian H, Huang J, Sha H, Zhang H, Yu L, Liu B, Hua D, Qian XP
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	biomimetic nanocarrier anti-EGFR-iRGD recombinant protein gambogic acid targeting ability anti-tumor efficiency colorectal cancer Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/1c20c04214e84ad88ede71b44077d224
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spelling	oai:doaj.org-article:1c20c04214e84ad88ede71b44077d2242021-12-02T04:51:59ZAnti-EGFR-iRGD recombinant protein modified biomimetic nanoparticles loaded with gambogic acid to enhance targeting and antitumor ability in colorectal cancer treatment1178-2013https://doaj.org/article/1c20c04214e84ad88ede71b44077d2242018-08-01T00:00:00Zhttps://www.dovepress.com/anti-egfr-irgd-recombinant-protein-modified-biomimetic-nanoparticles-l-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Zhen Zhang,1,2 Hanqing Qian,1 Jie Huang,1 Huizi Sha,1 Hang Zhang,1 Lixia Yu,1 Baorui Liu,1 Dong Hua,3 Xiaoping Qian1 1Comprehensive Cancer Center, Nanjing Drum Tower Hospital, Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Integrated Traditional Chinese Medicine and Western Medicine Oncology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, People’s Republic of China; 3Department of Medical Oncology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, People’s Republic of China Background: Red blood cell membrane-coated nanoparticle (RBCm-NP) platform, which consist of natural RBCm and synthetic polymeric core, can extend circulation time in vivo with an improved biocompatibility and stability of this biomimetic nanocarrier. To achieve better bioavailability of antitumor drugs that were loaded in RBCm-NPs, the functionalization of coated RBCm with specific targeting ability is essential. Bispecific recombinant protein anti-EGFR-iRGD, containing both tumor penetrating peptide (internalizing RGD peptide) and EGFR single-domain antibody (sdAb), seems to be an optimal targeting ligand for RBCm-NPs in the treatment of multiple tumors, especially colorectal cancer with high EGFR expression. Materials and methods: We modified the anti-EGFR-iRGD recombinant protein on the surface of RBCm-NPs by lipid insertion method to construct iE–RBCm–PLGA NPs and confirmed the presentation of active tumor-targeting ability in colorectal cancer models with high EGFR expression when compared with RBCm–PLGA NPs. In addition, potential anti- tumor drug gambogic acid (GA) was loaded into the NPs to endow the antitumor efficiency of iE–RBCm–GA/PLGA NPs. It was simultaneously evaluated whether GA can reach better biocompatibility benefiting from the improved antitumor efficiency of iE–RBCm–GA/PLGA NPs in colorectal cancer models. Results: We successfully modified anti-EGFR-iRGD proteins on the surface of biomimetic NPs with integrated and stable “shell–core” structure. iE–RBCm–PLGA NPs showed its improved targeting ability in vitro (multicellular spheroids [MCS]) and in vivo (nude mice bearing tumors). Besides, no matter on short-term cell apoptosis at tumor site (terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling [TUNEL]) and long-term tumor inhibition, iE–RBCm–GA/PLGA NPs achieved better antitumor efficacy than free GA in spite of the similar effects of cytotoxicity and apoptosis to GA in vitro. Conclusion: We expect that the bispecific biomimetic nanocarrier can extend the clinical application of many other potential antitumor drugs similar to GA and become a novel drug carrier in the colorectal cancer treatment. Keywords: biomimetic nanocarrier, anti-EGFR-iRGD recombinant protein, gambogic acid, targeting ability, antitumor efficiency, colorectal cancerZhang ZQian HHuang JSha HZhang HYu LLiu BHua DQian XPDove Medical Pressarticlebiomimetic nanocarrieranti-EGFR-iRGD recombinant proteingambogic acidtargeting abilityanti-tumor efficiencycolorectal cancerMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 4961-4975 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	biomimetic nanocarrier anti-EGFR-iRGD recombinant protein gambogic acid targeting ability anti-tumor efficiency colorectal cancer Medicine (General) R5-920
spellingShingle	biomimetic nanocarrier anti-EGFR-iRGD recombinant protein gambogic acid targeting ability anti-tumor efficiency colorectal cancer Medicine (General) R5-920 Zhang Z Qian H Huang J Sha H Zhang H Yu L Liu B Hua D Qian XP Anti-EGFR-iRGD recombinant protein modified biomimetic nanoparticles loaded with gambogic acid to enhance targeting and antitumor ability in colorectal cancer treatment
description	Zhen Zhang,1,2 Hanqing Qian,1 Jie Huang,1 Huizi Sha,1 Hang Zhang,1 Lixia Yu,1 Baorui Liu,1 Dong Hua,3 Xiaoping Qian1 1Comprehensive Cancer Center, Nanjing Drum Tower Hospital, Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Integrated Traditional Chinese Medicine and Western Medicine Oncology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, People’s Republic of China; 3Department of Medical Oncology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, People’s Republic of China Background: Red blood cell membrane-coated nanoparticle (RBCm-NP) platform, which consist of natural RBCm and synthetic polymeric core, can extend circulation time in vivo with an improved biocompatibility and stability of this biomimetic nanocarrier. To achieve better bioavailability of antitumor drugs that were loaded in RBCm-NPs, the functionalization of coated RBCm with specific targeting ability is essential. Bispecific recombinant protein anti-EGFR-iRGD, containing both tumor penetrating peptide (internalizing RGD peptide) and EGFR single-domain antibody (sdAb), seems to be an optimal targeting ligand for RBCm-NPs in the treatment of multiple tumors, especially colorectal cancer with high EGFR expression. Materials and methods: We modified the anti-EGFR-iRGD recombinant protein on the surface of RBCm-NPs by lipid insertion method to construct iE–RBCm–PLGA NPs and confirmed the presentation of active tumor-targeting ability in colorectal cancer models with high EGFR expression when compared with RBCm–PLGA NPs. In addition, potential anti- tumor drug gambogic acid (GA) was loaded into the NPs to endow the antitumor efficiency of iE–RBCm–GA/PLGA NPs. It was simultaneously evaluated whether GA can reach better biocompatibility benefiting from the improved antitumor efficiency of iE–RBCm–GA/PLGA NPs in colorectal cancer models. Results: We successfully modified anti-EGFR-iRGD proteins on the surface of biomimetic NPs with integrated and stable “shell–core” structure. iE–RBCm–PLGA NPs showed its improved targeting ability in vitro (multicellular spheroids [MCS]) and in vivo (nude mice bearing tumors). Besides, no matter on short-term cell apoptosis at tumor site (terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling [TUNEL]) and long-term tumor inhibition, iE–RBCm–GA/PLGA NPs achieved better antitumor efficacy than free GA in spite of the similar effects of cytotoxicity and apoptosis to GA in vitro. Conclusion: We expect that the bispecific biomimetic nanocarrier can extend the clinical application of many other potential antitumor drugs similar to GA and become a novel drug carrier in the colorectal cancer treatment. Keywords: biomimetic nanocarrier, anti-EGFR-iRGD recombinant protein, gambogic acid, targeting ability, antitumor efficiency, colorectal cancer
format	article
author	Zhang Z Qian H Huang J Sha H Zhang H Yu L Liu B Hua D Qian XP
author_facet	Zhang Z Qian H Huang J Sha H Zhang H Yu L Liu B Hua D Qian XP
author_sort	Zhang Z
title	Anti-EGFR-iRGD recombinant protein modified biomimetic nanoparticles loaded with gambogic acid to enhance targeting and antitumor ability in colorectal cancer treatment
title_short	Anti-EGFR-iRGD recombinant protein modified biomimetic nanoparticles loaded with gambogic acid to enhance targeting and antitumor ability in colorectal cancer treatment
title_full	Anti-EGFR-iRGD recombinant protein modified biomimetic nanoparticles loaded with gambogic acid to enhance targeting and antitumor ability in colorectal cancer treatment
title_fullStr	Anti-EGFR-iRGD recombinant protein modified biomimetic nanoparticles loaded with gambogic acid to enhance targeting and antitumor ability in colorectal cancer treatment
title_full_unstemmed	Anti-EGFR-iRGD recombinant protein modified biomimetic nanoparticles loaded with gambogic acid to enhance targeting and antitumor ability in colorectal cancer treatment
title_sort	anti-egfr-irgd recombinant protein modified biomimetic nanoparticles loaded with gambogic acid to enhance targeting and antitumor ability in colorectal cancer treatment
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/1c20c04214e84ad88ede71b44077d224
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Anti-EGFR-iRGD recombinant protein modified biomimetic nanoparticles loaded with gambogic acid to enhance targeting and antitumor ability in colorectal cancer treatment

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