{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2022,6,8]],"date-time":"2022-06-08T06:40:22Z","timestamp":1654670422094},"reference-count":0,"publisher":"American Association for Cancer Research (AACR)","issue":"11_Supplement","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2011,11,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Combining multi-targeted strategies with in vivo stable drug retention and increased intracellular delivery is a promising strategy to treat solid tumors. We have evaluated the therapeutic impact of targeting two different populations within the tumor microenvironment (endothelial and cancer cells), using the same F3 peptide-targeted sterically-stabilized pH-sensitive liposome containing doxorubicin. We have demonstrated that it targets the nucleolin receptor on a cell- and ligand-specific manner and has the ability to promote intracellular and triggered drug release into breast cancer cells (hormone-dependent and triple negative subtypes). We have further evidenced that the overexpression of nucleolin in several cancer cell lines of diverse histological origins. We have demonstrated that the unique combination of targeting specificity and intracellular triggered release of a therapeutic agent, doxorubicin, has resulted in enhanced cytotoxic activity in those specific cell lines, when compared to the non-targeted counterpart.<\/jats:p>\n               <jats:p>Active tumor accumulation of the radioactive lipid and drug tracers of targeted pH-sensitive liposomes, performed on Balb\/c nude female mice bearing breast tumors implanted orthotopically, was registered for a time-point as short as 4 h and reaching 48% of the injected dose\/g of tumor. In compliance to these data was the doxorubicin tumor-to-heart ratio of 80.8 for F3-targeted pH-sensitive liposomes vs 3.3 and 12.2 for the non-targeted and targeted non-pH-sensitive liposomes, respectively, 24 h post-injection. These data suggested a decrease on the potential dose-cumulative toxicity to the heart, namely relative to the non-targeted non-pH-sensitive counterpart. In mice treated with the F3-targeted pH-sensitive nanoparticle, significant decrease of the viable rim area (50%, accompanied by a strong necrosis) and microvascular density (80%) was observed. Moreover, suppression of invasion to surrounding healthy tissues was depicted, which may increase the probability of tumors falling in the category of \u201cnegative margins\u201d, with reduced risk of relapse. The clinical potential of such strategy was reinforced by the successful ex-vivo targeting studies, where specific cellular association was observed in tumor cells harvested from tumors of patients submitted to mastectomy and overexpressing the nucleolin receptor, independent of age, proliferation index, oestrogen, progesterone and HER2 receptor expression.<\/jats:p>\n               <jats:p>Overall, this work has demonstrated that the combination of tumor and vascular targeting with intracellular triggered release of the encapsulated drug is crucial for the successful therapeutic outcome of a nanotechnology-based strategy against a solid tumor, and should be considered for clinical evaluation. In addition, we have provided evidence of specific targeting to tumor cells of diverse histological origins with the same nanotechnology-based platform, which may be a breakthrough in the development of anticancer therapies, especially when considering tumor cell heterogeneity.<\/jats:p>\n               <jats:p>Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C233.<\/jats:p>","DOI":"10.1158\/1535-7163.targ-11-c233","type":"journal-article","created":{"date-parts":[[2012,6,27]],"date-time":"2012-06-27T06:38:41Z","timestamp":1340779121000},"page":"C233-C233","update-policy":"http:\/\/dx.doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Abstract C233: Limiting tumor invasion with multifunctional nanoparticle targeting the tumor microenvironment."],"prefix":"10.1158","volume":"10","author":[{"given":"Vera","family":"Moura","sequence":"first","affiliation":[{"name":"1CNC (Center for Neuroscience and Cell Biology) and FFUC, University of Coimbra, Coimbra, Portugal;"}]},{"given":"Manuela","family":"Lacerda","sequence":"additional","affiliation":[{"name":"2Portuguese Institute of Oncology FG, EPE, Coimbra, Portugal;"}]},{"given":"Paulo","family":"Figueiredo","sequence":"additional","affiliation":[{"name":"2Portuguese Institute of Oncology FG, EPE, Coimbra, Portugal;"}]},{"given":"M. Luisa","family":"Corvo","sequence":"additional","affiliation":[{"name":"3Research Institute for Medicines and Pharmaceutical Sciences and FFUL, University of Lisbon, Lisbon, Portugal;"}]},{"given":"M. Eugenia M.","family":"Cruz","sequence":"additional","affiliation":[{"name":"3Research Institute for Medicines and Pharmaceutical Sciences and FFUL, University of Lisbon, Lisbon, Portugal;"}]},{"given":"Raquel","family":"Soares","sequence":"additional","affiliation":[{"name":"4Department of Biochemistry, Faculty of Medicine, University of Porto, Porto, Portugal;"}]},{"given":"M. Conceicao Pedroso","family":"de Lima","sequence":"additional","affiliation":[{"name":"5CNC (Center for Neuroscience and Cell Biology) and FCTUC, University of Coimbra, Coimbra, Portugal."}]},{"given":"Sergio","family":"Simoes","sequence":"additional","affiliation":[{"name":"1CNC (Center for Neuroscience and Cell Biology) and FFUC, University of Coimbra, Coimbra, Portugal;"}]},{"given":"Joao Nuno","family":"Moreira","sequence":"additional","affiliation":[{"name":"1CNC (Center for Neuroscience and Cell Biology) and FFUC, University of Coimbra, Coimbra, Portugal;"}]}],"member":"1086","container-title":["Molecular Cancer Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/aacrjournals.org\/mct\/article\/10\/11_Supplement\/C233\/232084\/Abstract-C233-Limiting-tumor-invasion-with","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/mct\/article\/10\/11_Supplement\/C233\/232084\/Abstract-C233-Limiting-tumor-invasion-with","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,8]],"date-time":"2022-06-08T05:58:20Z","timestamp":1654667900000},"score":1,"resource":{"primary":{"URL":"https:\/\/aacrjournals.org\/mct\/article\/10\/11_Supplement\/C233\/232084\/Abstract-C233-Limiting-tumor-invasion-with"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,11]]},"references-count":0,"journal-issue":{"issue":"11_Supplement","published-print":{"date-parts":[[2011,11,12]]}},"URL":"https:\/\/doi.org\/10.1158\/1535-7163.targ-11-c233","relation":{},"ISSN":["1535-7163","1538-8514"],"issn-type":[{"value":"1535-7163","type":"print"},{"value":"1538-8514","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2011,11]]},"published":{"date-parts":[[2011,11]]}}}