Severity: Warning
Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
Line Number: 143
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 143
Function: file_get_contents
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 209
Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3098
Function: getPubMedXML
File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Attempt to read property "Count" on bool
Filename: helpers/my_audit_helper.php
Line Number: 3100
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3100
Function: _error_handler
File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
PEGylation has been widely applied to prolong the circulation times of nanomedicines the steric shielding effect, which consequently improves the intratumoral accumulation. However, cell uptake of PEGylated nanoformulations is always blocked by the steric repulsion of PEG, which limits their therapeutic effect. To this end, we designed and prepared two kinds of poly(l-glutamic acid)-cisplatin (PLG-CDDP) nanoformulations with detachable PEG, which is responsive to specific tumor tissue microenvironments for prolonged circulation time and enhanced cell internalization. The extracellular pH (pH)-responsive cleavage 2-propionic-3-methylmaleic anhydride (CDM)-derived amide bond and matrix metalloproteinases-2/9 (MMP-2/9)-sensitive degradable peptide PLGLAG were utilized to link PLG and PEG, yielding pH-responsive PEG- -PLG and MMP-sensitive PEG--PLG. The corresponding smart nanoformulations PEG- -PLG-Pt and PEG--PLG-Pt were then prepared by the complexation of polypeptides and cisplatin (CDDP). The circulation half-lives of PEG- -PLG-Pt and PEG--PLG-Pt were about 4.6 and 4.2 times higher than that of the control PLG-Pt, respectively. Upon reaching tumor tissue, PEG on the surface of nanomedicines was detached as triggered by pH or MMP, which increased intratumoral CDDP retention, enhanced cell uptake, and improved antitumor efficacy toward a fatal high-grade serous ovarian cancer (HGSOC) mouse model, indicating the promising prospects for clinical application of detachable PEGylated nanoformulations.
Download full-text PDF |
Source |
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895728 | PMC |
http://dx.doi.org/10.1016/j.bioactmat.2021.01.034 | DOI Listing |
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