Functional-segregated coumarin-containing telodendrimer nanocarriers for efficient delivery of SN-38 for colon cancer treatment

Gaofei Xu, Changying Shi, Dandan Guo, Lili Wang, Yun Ling, Xiaobing Han, Juntao Luo

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Four coumarin-containing telodendrimers (denoted as P-I, P-II, P-III and P-IV) were designed and synthesized to self-assemble into the corresponding nanoparticles. Of those, two nanoparticles (P-II and P-IV micelles) were screened and selected for targeted drug delivery of 7-ethyl-10-hydroxy camptothecin (SN-38), a prominent and efficacious anticancer agent, for the treatment of colon cancers. The nanoparticle encapsulation significantly increased the solubility of SN-38 in aqueous solution. Dynamic light scattering (DLS) showed the size of these SN-38 nanoparticles to be around 50 nm, and rod-shaped micelles were observed using transmission electron microscopy (TEM). These two novel nanoformulations of SN-38/P-II and SN-38/P-IV were found to exhibit similar in vitro cytotoxic activity against colon cancer cells as the free drug (SN-38 in DMSO) and were 500-fold more potent than irinotecan (a prodrug of SN-38). In addition, near infrared fluorescent (NIRF) optical imaging was utilized to monitor the tumor targeted delivery of SN-38/NPs via co-loading a NIRF dye. It was demonstrated that these NPs preferentially accumulated in tumors when compared to healthy tissue. A pharmacokinetics study showed that SN-38 micelle formulations had a longer circulating time in blood than irinotecan. Furthermore, SN-38 loaded nanoformulations exhibit superior anti-tumor efficacy when compared with irinotecan at equivalent SN-38 dose in HT-29 human colon cancer xenograft models.

Original languageEnglish (US)
Pages (from-to)85-98
Number of pages14
JournalActa Biomaterialia
Volume21
DOIs
StatePublished - Jul 15 2015
Externally publishedYes

Fingerprint

irinotecan
Oncology
Colonic Neoplasms
Micelles
Nanoparticles
Tumors
Infrared radiation
Pharmacokinetics
Dynamic light scattering
Encapsulation
Blood
Dyes
Solubility
Cells
Tissue
Transmission electron microscopy
Imaging techniques
coumarin

Keywords

  • Drug delivery
  • Irinotecan
  • Micelles
  • Nanomedicine
  • SN-38

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering
  • Biotechnology
  • Biochemistry
  • Molecular Biology

Cite this

Functional-segregated coumarin-containing telodendrimer nanocarriers for efficient delivery of SN-38 for colon cancer treatment. / Xu, Gaofei; Shi, Changying; Guo, Dandan; Wang, Lili; Ling, Yun; Han, Xiaobing; Luo, Juntao.

In: Acta Biomaterialia, Vol. 21, 15.07.2015, p. 85-98.

Research output: Contribution to journalArticle

Xu, Gaofei ; Shi, Changying ; Guo, Dandan ; Wang, Lili ; Ling, Yun ; Han, Xiaobing ; Luo, Juntao. / Functional-segregated coumarin-containing telodendrimer nanocarriers for efficient delivery of SN-38 for colon cancer treatment. In: Acta Biomaterialia. 2015 ; Vol. 21. pp. 85-98.
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