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
Cancer cells possess an efficient redox system, enabling them to withstand oxidative damage induced by treatments, especially in hypoxia areas and ferroptosis can disrupt redox homeostasis in cancer cell. Herein, GSH-sensitive nanoparticles are constructed that induce ferroptosis by long-lasting GSH depletion and enhanced PDT. Carbonic anhydrase IX inhibitor, protoporphyrin IX (Por) complexed with Fe and epirubicin (EPI) are grafted to hyaluronic acid (HA) via disulfide bonds to obtain HSPFE and loaded xCT inhibitor SAS for fabricating SAS@HSPFE which is actively targeted to deep hypoxic tumor cells, and explosively releasing EPI, Por-Fe complex and SAS due to at high GSH concentration. Specifically, SAS inhibited the GSH biosynthesis, and the generation of ROS by Por and the involvement of Fe in the Fenton reaction jointly facilitates oxidative stress. Besides, Fe reacted with excess HO to produce O, which continuously fuels PDT. GPX4 and SLC7A11 related to antioxidant defense are down-regulated, while ACSL4 and TFRC promoting lipid peroxidation and ROS accumulation are up-regulated, which enhanced ferroptosis by amplifying oxidative stress and suppressing antioxidant defense. SAS@HSPFE NPs revealed highly efficient antitumor effect in vivo study. This study provides a novel approach to cancer treatment by targeting redox imbalance.
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Source |
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http://dx.doi.org/10.1002/smll.202404299 | DOI Listing |
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