CRLX101 nanoparticles localize in human tumors and not in adjacent, nonneoplastic tissue after intravenous dosing.
Proc Natl Acad Sci U S A
; 113(14): 3850-4, 2016 Apr 05.
Article
em En
| MEDLINE
| ID: mdl-27001839
ABSTRACT
Nanoparticle-based therapeutics are being used to treat patients with solid tumors. Whereas nanoparticles have been shown to preferentially accumulate in solid tumors of animal models, there is little evidence to prove that intact nanoparticles localize to solid tumors of humans when systemically administered. Here, tumor and adjacent, nonneoplastic tissue biopsies are obtained through endoscopic capture from patients with gastric, gastroesophageal, or esophageal cancer who are administered the nanoparticle CRLX101. Both the pre- and postdosing tissue samples adjacent to tumors show no definitive evidence of either the nanoparticle or its drug payload (camptothecin, CPT) contained within the nanoparticle. Similar results are obtained from the predosing tumor samples. However, in nine of nine patients that were evaluated, CPT is detected in the tumor tissue collected 24-48 h after CRLX101 administration. For five of these patients, evidence of the intact deposition of CRLX101 nanoparticles in the tumor tissue is obtained. Indications of CPT pharmacodynamics from tumor biomarkers such as carbonic anhydrase IX and topoisomerase I by immunohistochemistry show clear evidence of biological activity from the delivered CPT in the posttreatment tumors.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Gástricas
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Camptotecina
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Neoplasias Esofágicas
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Ciclodextrinas
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Nanopartículas
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Antineoplásicos Fitogênicos
Limite:
Animals
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Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2016
Tipo de documento:
Article