Targeting tumor vasculature with aptamer-functionalized doxorubicin-polylactide nanoconjugates for enhanced cancer therapy

Li Tang, Rong Tong, Virginia J. Coyle, Qian Yin, Holly Pondenis, Luke B. Borst, Jianjun Cheng, Timothy M. Fan

Research output: Contribution to journalArticlepeer-review


An A10 aptamer (Apt)-functionalized, sub-100 nm doxorubicin-polylactide (Doxo-PLA) nanoconjugate (NC) with controlled release profile was developed as an intravenous therapeutic strategy to effectively target and cytoreduce canine hemangiosarcoma (cHSA), a naturally occurring solid tumor malignancy composed solely of tumor-associated endothelium. cHSA consists of a pure population of malignant endothelial cells expressing prostate-specific membrane antigen (PSMA) and is an ideal comparative tumor model system for evaluating the specificity and feasibility of tumor-associated endothelial cell targeting by A10 Apt-functionalized NC (A10 NC). In vitro, A10 NCs were selectively internalized across a panel of PSMA-expressing cancer cell lines, and when incorporating Doxo, A10 Doxo-PLA NCs exerted greater cytotoxic effects compared to nonfunctionalized Doxo-PLA NCs and free Doxo. Importantly, intravenously delivered A10 NCs selectively targeted PSMA-expressing tumor-associated endothelial cells at a cellular level in tumor-bearing mice and dramatically increased the uptake of NCs by endothelial cells within the local tumor microenvironment. By virtue of controlled drug release kinetics and selective tumor-associated endothelial cell targeting, A10 Doxo-PLA NCs possess a desirable safety profile in vivo, being well-tolerated following high-dose intravenous infusion in mice, as supported by the absence of any histologic organ toxicity. In cHSA-implanted mice, two consecutive intravenous infusions of A10 Doxo-PLA NCs exerted rapid and substantial cytoreductive activities within a period of 7 days, resulting in greater than 70% reduction in macroscopic tumor-associated endothelial cell burden as a consequence of enhanced cell death and necrosis.

Original languageEnglish (US)
Pages (from-to)5072-5081
Number of pages10
JournalACS Nano
Issue number5
StatePublished - May 26 2015


  • cancer targeting by aptamer
  • comparative tumor model
  • nanoconjugate drug delivery
  • prostate-specific membrane antigen
  • tumor-associated endothelium

ASJC Scopus subject areas

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


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