{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T01:06:06Z","timestamp":1760231166261,"version":"build-2065373602"},"reference-count":50,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,8,28]],"date-time":"2022-08-28T00:00:00Z","timestamp":1661644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Patients undergoing immunotherapy always exhibit a low-response rate due to tumor heterogeneity and immune surveillance in the tumor. Angiogenesis plays an important role in affecting the status of tumor-infiltrated lymphocytes by inducing hypoxia and acidosis microenvironment, suggesting its synergistic potential in immunotherapy. However, the antitumor efficacy of singular anti-angiogenesis therapy often suffers from failure in the clinic due to the compensatory pro-angiogenesis signaling pathway. In this work, classic injectable thermosensitive PLGA-PEG-PLGA copolymer was used to construct a platform to co-deliver CA4P (vascular disruptive agent) and EPI for inducing immunogenic cell death of cancer cells by targeting the tumor immune microenvironment. Investigation of 4T1 tumor-bearing mouse models suggests that local administration of injectable V+E@Gel could significantly inhibit the proliferation of cancer cells and prolong the survival rate of 4T1 tumor-bearing mouse models. Histological analysis further indicates that V+E@Gel could effectively inhibit tumor angiogenesis and metastasis by down-regulating the expression of CD34, CD31, MTA1 and TGF-\u03b2. Moreover, due to the sustained release kinetics of V+E@Gel, its local administration relieves the immune surveillance in tumor tissues and thus induces a robust and long-lasting specific antitumor immune response. Overall, this work provides a new treatment strategy through the mediation of the tumor immune microenvironment by vascular disruption to fulfill enhanced chemotherapy and immunotherapy.<\/jats:p>","DOI":"10.3390\/pharmaceutics14091809","type":"journal-article","created":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T22:53:42Z","timestamp":1661813622000},"page":"1809","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Vascular Disruptive Hydrogel Platform for Enhanced Chemotherapy and Anti-Angiogenesis through Alleviation of Immune Surveillance"],"prefix":"10.3390","volume":"14","author":[{"given":"Fasheng","family":"Li","sequence":"first","affiliation":[{"name":"Department of Imaging, The Fifth Affiliated Hospital of Jinan University, Jinan University, Heyuan 517000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinmei","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Fifth Affiliated Hospital of Jinan University, Jinan University, Heyuan 517000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dehui","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Imaging, The Fifth Affiliated Hospital of Jinan University, Jinan University, Heyuan 517000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaogang","family":"Jiao","sequence":"additional","affiliation":[{"name":"Department of Imaging, The Fifth Affiliated Hospital of Jinan University, Jinan University, Heyuan 517000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinqi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Imaging, The Fifth Affiliated Hospital of Jinan University, Jinan University, Heyuan 517000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wencai","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Interventional, The Fifth Affiliated Hospital of Jinan University, Jinan University, Heyuan 517000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9753-9584","authenticated-orcid":false,"given":"Xiaoyan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Fifth Affiliated Hospital of Jinan University, Jinan University, Heyuan 517000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"109821","DOI":"10.1016\/j.biopha.2020.109821","article-title":"Cancer immunotherapy: Pros, cons and beyond","volume":"124","author":"Tan","year":"2020","journal-title":"Biomed. 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