Nanotherapeutic approaches to overcome distinct drug resistance barriers in models of breast cancer

Tanmoy Saha, Jayanta Mondal, Sachin Khiste, Hrvoje Lusic, Zhang Wei Hu, Ruparoshni Jayabalan, Kevin J. Hodgetts, Haelin Jang, Shiladitya Sengupta, Somin Eunice Lee, Younggeun Park, Luke P. Lee, Aaron Goldman

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Targeted delivery of drugs to tumor cells, which circumvent resistance mechanisms and induce cell killing, is a lingering challenge that requires innovative solutions. Here, we provide two bioengineered strategies in which nanotechnology is blended with cancer medicine to preferentially target distinct mechanisms of drug resistance. In the first 'case study', we demonstrate the use of lipid-drug conjugates that target molecular signaling pathways, which result from taxane-induced drug tolerance via cell surface lipid raft accumulations. Through a small molecule drug screen, we identify a kinase inhibitor that optimally destroys drug tolerant cancer cells and conjugate it to a rationally-chosen lipid scaffold, which enhances anticancer efficacy in vitro and in vivo. In the second 'case study', we address resistance mechanisms that can occur through exocytosis of nanomedicines. Using adenocarcinoma HeLa and MCF-7 cells, we describe the use of gold nanorod and nanoporous vehicles integrated with an optical antenna for on-demand, photoactivation at ∼650 nm enabling release of payloads into cells including cytotoxic anthracyclines. Together, these provide two approaches, which exploit engineering strategies capable of circumventing distinct resistance barriers and induce killing by multimodal, including nanophotonic mechanisms.

Original languageEnglish
Pages (from-to)3063-3073
Number of pages11
JournalNanophotonics
Volume10
Issue number12
DOIs
StatePublished - 2 Sep 2021

Bibliographical note

Publisher Copyright:
© 2021 Tanmoy Saha et al., published by De Gruyter, Berlin/Boston.

Keywords

  • cancer biology
  • chemotherapy
  • drug resistance
  • nanomedicine

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