A tumor-penetrating recombinant protein anti-EGFR-iRGD enhance efficacy of paclitaxel in 3D multicellular spheroids and gastric cancer in vivo

Sha, Huizi; Li, Rutian; Bian, Xinyu; Liu, Qin; Xie, Chen; Xin, Xiaoyan; Kong, Weiwei; Qian, Xiaoping; Jiang, Xiqun; Hu, Weixin; Liu, Baorui

doi:10.1016/j.ejps.2015.05.020

Cited by 24 publications

(25 citation statements)

References 31 publications

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“…Therefore, the combination of iRGD peptide and EGFR antibody seems to be desired for targeting ligands in colorectal cancer. In our previous research, we have constructed a new recombinant protein named anti-EGFR-iRGD, 48,49 containing both iRGD peptide and EGFR single-domain antibody (sdAb). [50][51][52][53] Besides, we also confirmed the dual targeting ability and improved synergistic antitumor effect with antitumor drugs for anti-EGFR-iRGD recombinant protein.…”

Section: Introductionmentioning

confidence: 99%

“…[50][51][52][53] Besides, we also confirmed the dual targeting ability and improved synergistic antitumor effect with antitumor drugs for anti-EGFR-iRGD recombinant protein. 48,49,54,55 Thus, it can be seen that anti-EGFR-iRGD recombinant protein is expected to an optimal targeting ligand for RBCm NPs to achieve better tumor-targeting ability and antitumor efficiency.…”

Section: Introductionmentioning

confidence: 99%

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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

Zhang

Huang

et al. 2018

IJN

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BackgroundRed 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 methodsWe 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.ResultsWe 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.ConclusionWe 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.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Zhang

Huang

et al. 2018

IJN

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“…Recombinant protein anti-EGFR-iRGD was prepared as previously reported. 29,30 The anti-EGFR-iRGD was then used to prepare DSPE-PEG-anti-EGFR-iRGD, using a method previously reported. 28,31 In brief, DSPE-PEG-MAL was mixed with anti-EGFR-iRGD at a 1:1 molar ratio (anti-EGFR-iRGD:DSPE-PEG-MAL =1:1) in Hepes (pH=6.5).…”

Section: Synthesis Of Anti-egfr-irgd and Dspe-peg-anti-egfr-irgdmentioning

confidence: 99%

“…Here, we report a novel tumor-targeting delivery system for PTX. This nanosystem uses RBCm-derived microvesicles as carriers for PTX, with anti-EGFR-iRGD, a recombinant protein that was designed and manufactured by our team, 29,30 as a tumor-targeting molecule. The manufacturing procedure for this nanosystem is illustrated in Figure 1.…”

Section: Introductionmentioning

confidence: 99%

Lipid insertion enables targeted functionalization of paclitaxel-loaded erythrocyte membrane nanosystem by tumor-penetrating bispecific recombinant protein

Chen

Sha

Zhang

et al. 2018

IJN

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BackgroundThere is currently much interest in cancer cell targeting and tumor penetrating for research and therapeutic purposes.PurposeTo improve targeting delivery of antitumor drugs to gastric cancer, in this study, a tumor-targeting biocompatible drug delivery system derived from erythrocyte membrane for delivering paclitaxel (PTX) was constructed.MethodsErythrocyte membrane of human red blood cells (RBCs) were used for preparing of erythrocyte membrane-derived vesicles. 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-(maleimide[polyethylene glycol]-3400) (DSPE-PEG-MAL), a phospholipid derivative, was used to insert tumor-targeting molecular into erythrocyte membrane-derived vesicles. A lipid insertion method was used to functionalize these vesicles without the need for direct chemical conjugation. Furthermore, a tumor-penetrating bispecific recombinant protein named anti-EGFR-iRGD was used for the first time in this work to enable nanosystem to target and penetrate efficiently into the tumor site.ResultsPaclitaxel (PTX)-loaded anti-EGFR-iRGD-modified erythrocyte membrane nano-system (anti-EGFR-iRGD-RBCm-PTX, abbreviated to PRP) were manufactured. PRP was spheroid, uniformly size, about 171.7±4.7 nm in average, could be stable in vitro for 8 days, and released PTX in a biphasic pattern. PRP showed comparable cytotoxicity toward human gastric cancer cells in vitro. In vivo studies showed that, PRP accumulated in tumor site within 2 h of administration, lasted longer than 48 h, and the tumor volume was reduced 61% by PRP treatment in Balb/c nude mice, without causing severe side effects.ConclusionPRP has potential applications in cancer treatment and as an adjunct for other anticancer strategies.

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“…The traditional treatment usually leads to severe bone marrow suppression, hair loss, and other side effects. Recently, several strategies have been explored to improve the specificity and effectiveness of antitumor drugs [7][8][9][10][11]. One novel strategy is to develop nontoxic prodrugs that can be activated by specific signals, including redox, pH, light, enzyme [12][13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

A novel o-nitrobenzyl-based photocleavable antitumor prodrug with the capability of releasing 5-fluorourail

Wen

Xue

et al. 2016

Science Bulletin

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A tumor-penetrating recombinant protein anti-EGFR-iRGD enhance efficacy of paclitaxel in 3D multicellular spheroids and gastric cancer in vivo

Cited by 24 publications

References 31 publications

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

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

Lipid insertion enables targeted functionalization of paclitaxel-loaded erythrocyte membrane nanosystem by tumor-penetrating bispecific recombinant protein

A novel o-nitrobenzyl-based photocleavable antitumor prodrug with the capability of releasing 5-fluorourail

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