{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T16:10:35Z","timestamp":1790179835069,"version":"4.1.0"},"reference-count":278,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,26]],"date-time":"2024-01-26T00:00:00Z","timestamp":1706227200000},"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>Solid tumors are composed of a highly complex and heterogenic microenvironment, with increasing metabolic status. This environment plays a crucial role in the clinical therapeutic outcome of conventional treatments and innovative antitumor nanomedicines. Scientists have devoted great efforts to conquering the challenges of the tumor microenvironment (TME), in respect of effective drug accumulation and activity at the tumor site. The main focus is to overcome the obstacles of abnormal vasculature, dense stroma, extracellular matrix, hypoxia, and pH gradient acidosis. In this endeavor, nanomedicines that are targeting distinct features of TME have flourished; these aim to increase site specificity and achieve deep tumor penetration. Recently, research efforts have focused on the immune reprograming of TME in order to promote suppression of cancer stem cells and prevention of metastasis. Thereby, several nanomedicine therapeutics which have shown promise in preclinical studies have entered clinical trials or are already in clinical practice. Various novel strategies were employed in preclinical studies and clinical trials. Among them, nanomedicines based on biomaterials show great promise in improving the therapeutic efficacy, reducing side effects, and promoting synergistic activity for TME responsive targeting. In this review, we focused on the targeting mechanisms of nanomedicines in response to the microenvironment of solid tumors. We describe responsive nanomedicines which take advantage of biomaterials\u2019 properties to exploit the features of TME or overcome the obstacles posed by TME. The development of such systems has significantly advanced the application of biomaterials in combinational therapies and in immunotherapies for improved anticancer effectiveness.<\/jats:p>","DOI":"10.3390\/pharmaceutics16020179","type":"journal-article","created":{"date-parts":[[2024,1,26]],"date-time":"2024-01-26T10:54:27Z","timestamp":1706266467000},"page":"179","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Biomaterial-Based Responsive Nanomedicines for Targeting Solid Tumor Microenvironments"],"prefix":"10.3390","volume":"16","author":[{"given":"Konstantinos","family":"Avgoustakis","sequence":"first","affiliation":[{"name":"Department of Pharmacy, School of Health Sciences, University of Patras, 26504 Patras, Greece"},{"name":"Clinical Studies Unit, Biomedical Research Foundation Academy of Athens (BRFAA), 4 Soranou Ephessiou Street, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7277-1590","authenticated-orcid":false,"given":"Athina","family":"Angelopoulou","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Polytechnic School, University of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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