HFT-T, a targeting nanoparticle, enhances specific delivery of paclitaxel to folate receptor-positive tumors

Xu Wang, Jun Li, Yiqing Wang, Kwang Jae Cho, Gloria Kim, Ada Gjyrezi, Lydia Koenig, Paraskevi Giannakakou, Hyung Ju C Shin, Mourad Tighiouart, Shuming Nie, Zhuo Chen, Dong M. Shin

Research output: Contribution to journalArticlepeer-review

146 Scopus citations

Abstract

Nonspecific distribution of chemotherapeutic drugs (such as paclitaxel) is a major factor contributing to side effects and poor clinical outcomes in the treatment of human head and neck cancer. To develop novel drug delivery systems with enhanced efficacy and minimized adverse effects, we synthesized a ternary conjugate heparin-folic acid-paclitaxel (HFT), loaded with additional paclitaxel (T). The resulting nanoparticle, HFT-T, is expected to retain the antitumor activity of paclitaxel and specifically target folate receptor (FR)-expressing tumors, thereby increasing the bioavailability and efficacy of paclitaxel. In vitro experiments found that HFT-T selectively recognizes FR-positive human head and neck cancer cell line KB-3-1, displaying higher cytotoxicity compared to the free form of paclitaxel. In a subcutaneous KB-3-1 xenograft model, HFT-T administration enhanced the specific delivery of paclitaxel into tumor tissues and remarkably improved antitumor efficacy of paclitaxel. The average tumor volume in the HFT-T treatment group was 92.9 ± 78.2 mm3 vs 1670.3 ± 286.1 mm3 in the mice treated with free paclitaxel. Furthermore, paclitaxel tumors showed a resurgence of growth after several weeks of treatment, but this was not observed with HFT-T. This indicates that HFT-T could be more effective in preventing tumors from developing drug resistance. No significant acute in vivo toxicity was observed. These results indicate that specific delivery of paclitaxel with a ternary structured nanoparticle (HFT-T) targeting FR-positive tumor is a promising strategy to enhance chemotherapy efficacy and minimize adverse effects.

Original languageEnglish (US)
Pages (from-to)3165-3174
Number of pages10
JournalACS nano
Volume3
Issue number10
DOIs
StatePublished - Oct 27 2009

Keywords

  • Chemotherapy
  • Folate receptor
  • Paclitaxel
  • Specific drug delivery
  • Targeting nanoparticle

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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