Light-Controlled Simultaneous "On Demand" Release of Cytotoxic Combinations for Bimodal Killing of Cancer Cells

Chemistry. 2018 May 28;24(30):7664-7670. doi: 10.1002/chem.201800862. Epub 2018 May 3.

Abstract

In this contribution, we report a novel entirely photocontrolled nanoplatform comprising a binary mixture of pluronic copolymers capable of self-assembling into core-shell micelles and co-entrapping two photoactivatable components: a benzoporphyrin photosensitizer for photodynamic therapy (PDT) and coumarin-photocaged chemotherapeutic agent Chlorambucil (CAB). The resulting supramolecular micellar assembly is about 30 nm in diameter with a polydispersity index <0.1, stable for more than 72 h, and exhibits excellent preservation of the photochemical properties of the two photoresponsive components, even though they are confined within the same host nanocarrier. Appropriate regulation of the relative concentrations of these components makes them capable of absorbing visible light in comparable amounts, leading to effective simultaneous photogeneration of singlet oxygen and photo-triggered release of CAB. This "on demand" release of cytotoxic combinations results in amplified anticancer activity against MCF-7 human breast adenocarcinoma cells.

Keywords: chemotherapy; cytotoxicity; micelles; multimodal therapy; photodynamic therapy.

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Humans
  • MCF-7 Cells
  • Micelles
  • Photochemotherapy
  • Photosensitizing Agents / chemistry*
  • Singlet Oxygen / chemistry*

Substances

  • Antineoplastic Agents
  • Micelles
  • Photosensitizing Agents
  • Singlet Oxygen