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Site-Specific Drug-Releasing Polypeptide Nanocarriers Based on Dual-pH Response for Enhanced Therapeutic Efficacy against Drug-Resistant Tumors.

Dong Y, Yang J, Liu H, Wang T, Tang S, Zhang J, Zhang X - Theranostics (2015)

Bottom Line: To enhance effective drug accumulation in drug-resistant tumors, a site-specific drug-releasing polypeptide system (PEG-Phis/Pasp-DOX/CA4) was exploited in response to tumor extracellular and intracellular pH.This system could firstly release the embedded tumor vascular inhibitor (CA4) to transiently 'normalize' vasculature and facilitate drug internalization to tumors efficiently, and then initiate the secondary pH-response to set the conjugated active anticancer drug (DOX) free in tumor cells.The encapsulated system (PEG-Phis/DOX/CA4), both CA4 and DOX embedding in the nanoparticles, was used as a control.

View Article: PubMed Central - PubMed

Affiliation: 1. National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, China ; 2. College of Chemistry & Environmental Science, Chemical Biology Key Laboratory of Hebei Province, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Hebei University, Baoding, 071002, China.

ABSTRACT
To enhance effective drug accumulation in drug-resistant tumors, a site-specific drug-releasing polypeptide system (PEG-Phis/Pasp-DOX/CA4) was exploited in response to tumor extracellular and intracellular pH. This system could firstly release the embedded tumor vascular inhibitor (CA4) to transiently 'normalize' vasculature and facilitate drug internalization to tumors efficiently, and then initiate the secondary pH-response to set the conjugated active anticancer drug (DOX) free in tumor cells. The encapsulated system (PEG-Phis/DOX/CA4), both CA4 and DOX embedding in the nanoparticles, was used as a control. Comparing with PEG-Phis/DOX/CA4, PEG-Phis/Pasp-DOX/CA4 exhibited enhanced cytotoxicity against DOX-sensitive and DOX-resistant cells (MCF-7 and MCF-7/ADR). Moreover, PEG-Phis/Pasp-DOX/CA4 resulted in enhanced therapeutic efficacy in drug-resistant tumors with reduced toxicity. These results suggested that this site-specific drug-releasing system could be exploited as a promising treatment for cancers with repeated administration.

No MeSH data available.


Related in: MedlinePlus

Tumor sections were immunostained with TUNEL staining for tumor cell apoptosis after treatment with different formulations. Brown stains indicated apoptotic cells in TUNEL analysis.
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Figure 11: Tumor sections were immunostained with TUNEL staining for tumor cell apoptosis after treatment with different formulations. Brown stains indicated apoptotic cells in TUNEL analysis.

Mentions: The cell apoptosis in the tumor tissues after treatments was also analyzed using TUNEL assay (Figure 11) and hematoxylin-eosin (H&E) staining (Supplementary Material: Figure S17). Compared with other formulations, PEG-Phis60/Pasp-DOX/CA4 markedly increased the number of TUNEL-positive tumor cells (brown color). H&E staining of the tumors also showed the same tendency. The tumor tissues treated with PEG-Phis60/Pasp-DOX/CA4 lost their normal structures, and the tumor cellularity significantly decreased. These results were consistent with the higher inhibition of the tumor growth induced by PEG-Phis60/Pasp-DOX/CA4.


Site-Specific Drug-Releasing Polypeptide Nanocarriers Based on Dual-pH Response for Enhanced Therapeutic Efficacy against Drug-Resistant Tumors.

Dong Y, Yang J, Liu H, Wang T, Tang S, Zhang J, Zhang X - Theranostics (2015)

Tumor sections were immunostained with TUNEL staining for tumor cell apoptosis after treatment with different formulations. Brown stains indicated apoptotic cells in TUNEL analysis.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4440445&req=5

Figure 11: Tumor sections were immunostained with TUNEL staining for tumor cell apoptosis after treatment with different formulations. Brown stains indicated apoptotic cells in TUNEL analysis.
Mentions: The cell apoptosis in the tumor tissues after treatments was also analyzed using TUNEL assay (Figure 11) and hematoxylin-eosin (H&E) staining (Supplementary Material: Figure S17). Compared with other formulations, PEG-Phis60/Pasp-DOX/CA4 markedly increased the number of TUNEL-positive tumor cells (brown color). H&E staining of the tumors also showed the same tendency. The tumor tissues treated with PEG-Phis60/Pasp-DOX/CA4 lost their normal structures, and the tumor cellularity significantly decreased. These results were consistent with the higher inhibition of the tumor growth induced by PEG-Phis60/Pasp-DOX/CA4.

Bottom Line: To enhance effective drug accumulation in drug-resistant tumors, a site-specific drug-releasing polypeptide system (PEG-Phis/Pasp-DOX/CA4) was exploited in response to tumor extracellular and intracellular pH.This system could firstly release the embedded tumor vascular inhibitor (CA4) to transiently 'normalize' vasculature and facilitate drug internalization to tumors efficiently, and then initiate the secondary pH-response to set the conjugated active anticancer drug (DOX) free in tumor cells.The encapsulated system (PEG-Phis/DOX/CA4), both CA4 and DOX embedding in the nanoparticles, was used as a control.

View Article: PubMed Central - PubMed

Affiliation: 1. National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, China ; 2. College of Chemistry & Environmental Science, Chemical Biology Key Laboratory of Hebei Province, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Hebei University, Baoding, 071002, China.

ABSTRACT
To enhance effective drug accumulation in drug-resistant tumors, a site-specific drug-releasing polypeptide system (PEG-Phis/Pasp-DOX/CA4) was exploited in response to tumor extracellular and intracellular pH. This system could firstly release the embedded tumor vascular inhibitor (CA4) to transiently 'normalize' vasculature and facilitate drug internalization to tumors efficiently, and then initiate the secondary pH-response to set the conjugated active anticancer drug (DOX) free in tumor cells. The encapsulated system (PEG-Phis/DOX/CA4), both CA4 and DOX embedding in the nanoparticles, was used as a control. Comparing with PEG-Phis/DOX/CA4, PEG-Phis/Pasp-DOX/CA4 exhibited enhanced cytotoxicity against DOX-sensitive and DOX-resistant cells (MCF-7 and MCF-7/ADR). Moreover, PEG-Phis/Pasp-DOX/CA4 resulted in enhanced therapeutic efficacy in drug-resistant tumors with reduced toxicity. These results suggested that this site-specific drug-releasing system could be exploited as a promising treatment for cancers with repeated administration.

No MeSH data available.


Related in: MedlinePlus