Inhibiting Solid Tumor Growth In Vivo by Non-Tumor-Penetrating Nanomedicine

Shixian Lv, Zhaohui Tang, Wantong Song, Dawei Zhang, Mingqiang Li, Huaiyu Liu, Jianjun Cheng, Wu Zhong, Xuesi Chen

Research output: Contribution to journalArticlepeer-review

Abstract

Nanomedicine (NM) cannot penetrate deeply into solid tumors, which is partly attributed to the heterogeneous microenvironment and high interstitial fluid pressure of solid tumors. To improve NM efficacy, there has been tremendous effort developing tumor-penetrating NMs by miniaturizing NM sizes or controlling NM surface properties. But progress along the direction of developing tumor penetrating nanoparticle has been slow and improvement of the overall antitumor efficacy has been limited. Herein, a novel strategy of inhibiting solid tumor with high efficiency by dual-functional, nontumor-penetrating NM is demonstrated. The intended NM contains 5,6-dimethylxanthenone-4-acetic acid (DMXAA), a vascular-disrupting agent, and doxorubicin (DOX), a cytotoxic drug. Upon arriving at the target tumor site, sustained release of DMXAA from NMs results in disruption of tumor vessel functions, greatly inhibiting the interior tumor cells by cutting off nutritional supply. Meanwhile, the released DOX kills the residual cells at the tumor exterior regions. The in vivo studies demonstrate that this dual-functional, nontumor penetrating NM exhibits superior anticancer activity, revealing an alternative strategy of effective tumor growth inhibition.

Original languageEnglish (US)
Article number1600954
JournalSmall
Volume13
Issue number12
DOIs
StatePublished - Mar 28 2017

Keywords

  • chemotherapy
  • drug combination
  • nanomedicine
  • tumor penetration
  • vascular-disrupting agent

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Chemistry(all)
  • Materials Science(all)

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