CRLX101 nanoparticles localize in human tumors and not in adjacent, nonneoplastic tissue after intravenous dosing

Andrew J. Clark, Devin T. Wiley, Jonathan E. Zuckerman, Paul Webster, Joseph Chao, James Lin, Yun Yen, Mark E. Davis

研究成果: 雜誌貢獻文章

70 引文 (Scopus)

摘要

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.
原文英語
頁(從 - 到)3850-3854
頁數5
期刊Proceedings of the National Academy of Sciences of the United States of America
113
發行號14
DOIs
出版狀態已發佈 - 四月 5 2016

指紋

Nanoparticles
Camptothecin
Neoplasms
Carbonic Anhydrase I
IT-101
Type I DNA Topoisomerase
Esophageal Neoplasms
Tumor Biomarkers
Stomach Neoplasms
Animal Models
Immunohistochemistry
Biopsy
Pharmaceutical Preparations

ASJC Scopus subject areas

  • General

引用此文

CRLX101 nanoparticles localize in human tumors and not in adjacent, nonneoplastic tissue after intravenous dosing. / Clark, Andrew J.; Wiley, Devin T.; Zuckerman, Jonathan E.; Webster, Paul; Chao, Joseph; Lin, James; Yen, Yun; Davis, Mark E.

於: Proceedings of the National Academy of Sciences of the United States of America, 卷 113, 編號 14, 05.04.2016, p. 3850-3854.

研究成果: 雜誌貢獻文章

Clark, Andrew J. ; Wiley, Devin T. ; Zuckerman, Jonathan E. ; Webster, Paul ; Chao, Joseph ; Lin, James ; Yen, Yun ; Davis, Mark E. / CRLX101 nanoparticles localize in human tumors and not in adjacent, nonneoplastic tissue after intravenous dosing. 於: Proceedings of the National Academy of Sciences of the United States of America. 2016 ; 卷 113, 編號 14. 頁 3850-3854.
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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.",
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