Polymeric nanotheranostics for real-time non-invasive optical imaging of breast cancer progression and drug release

Shiran Ferber, Hemda Baabur-Cohen, Rachel Blau, Yana Epshtein, Einat Kisin-Finfer, Orit Redy, Doron Shabat, Ronit Satchi-Fainaro*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Polymeric nanocarriers conjugated with low molecular weight drugs are designed in order to improve their efficacy and toxicity profile. This approach is particularly beneficial for anticancer drugs, where the polymer-drug conjugates selectively accumulate at the tumor site, due to the enhanced permeability and retention (EPR) effect. The conjugated drug is typically inactive, and upon its pH- or enzymatically-triggered release from the carrier, it regains its therapeutic activity. These settings lack information regarding drug-release time, kinetics and location. Thereby, real-time non-invasive intravital monitoring of drug release is required for theranostics (therapy and diag. nostics). We present here the design, synthesis and characterization of a theranostic nanomedicine, based on N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer, owing its fluorescence-based monitoring of site-specific drug release to a self-quenched near-infrared fluorescence (NIRF) probe. We designed two HPMA copolymer-based systems that complement to a theranostic nanomedicine. The diagnostic system consists of self-quenched Cy5 (SQ-Cy5) as a reporter probe and the therapeutic system is based on the anticancer agent paclitaxel (PTX). HPMA copolymer-PTX/SQ-Cy5 systems enable site-specific release upon enzymatic degradation in cathepsin B-overexpressing breast cancer cells. The release of the drug occurs concomitantly with the activation of the fluorophore to its Turn-ON state. HPMA copolymer-SQ-Cy5 exhibits preferable body distribution and drug release compared with the free drug and probe when administered to cathepsin B-overexpressing 4T1 murine mammary adenocarcinoma-bearing mice. This approach of co-delivery of two complementary systems serves as a proof-of-concept for real-time deep tissue intravital orthotopic monitoring and may have the potential use in clinical utility as a theranostic nanomedicine.

Original languageEnglish
Pages (from-to)81-89
Number of pages9
JournalCancer Letters
Volume352
Issue number1
DOIs
StatePublished - 28 Sep 2014

Keywords

  • Breast cancer
  • NIR fluorophore
  • Paclitaxel
  • Polymeric nanomedicines
  • Theranostics
  • Tumor targeting

Fingerprint

Dive into the research topics of 'Polymeric nanotheranostics for real-time non-invasive optical imaging of breast cancer progression and drug release'. Together they form a unique fingerprint.

Cite this