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pH-responsive dendritic core-multishell nanocarriers.

Emanuel Fleige1, Katharina Achazi1, Karolina Schaletzki1

  • 1Freie Universität Berlin, Institut für Chemie und Biochemie, Takustraße 3, 14195 Berlin, Germany.

Journal of Controlled Release : Official Journal of the Controlled Release Society
|April 29, 2014
PubMed
Summary
This summary is machine-generated.

Novel pH-responsive core-multishell nanocarriers (pH-CMS) efficiently deliver anticancer drugs. The pH-labile imine linker enables targeted drug release in acidic intracellular environments, enhancing therapeutic efficacy.

Keywords:
DoxorubicinDrug deliveryDynamic light scatteringNile redReal time cell analysisTransport capacity

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Area of Science:

  • Nanotechnology
  • Materials Science
  • Chemistry

Background:

  • Development of advanced nanocarriers for targeted drug delivery is crucial in cancer therapy.
  • pH-responsive materials offer potential for controlled release of therapeutics within specific cellular compartments.
  • Core-multishell (CMS) nanocarriers provide a versatile platform for encapsulating and delivering various payloads.

Purpose of the Study:

  • To synthesize and characterize novel pH-responsive core-multishell (CMS) nanocarriers (pH-CMS) utilizing an aromatic imine linker.
  • To investigate the pH-dependent cleavage of the imine linker and its impact on nanocarrier stability.
  • To evaluate the loading and release characteristics of Nile red (NR) and doxorubicin (DOX) using these pH-CMS nanocarriers.

Main Methods:

  • Synthesis of pH-responsive core-multishell (CMS) nanocarriers with an imine linker.
  • Nuclear Magnetic Resonance (NMR) spectroscopy to confirm imine linker cleavage at low pH.
  • UV/Vis spectroscopy to determine dye (NR) and drug (DOX) loading capacities.
  • Dynamic Light Scattering (DLS) to analyze nanocarrier size before and after loading.
  • In vitro cellular studies to assess the toxicity of drug-loaded nanocarriers.

Main Results:

  • The synthesized pH-CMS nanocarriers exhibited rapid cleavage of the imine linker at pH 5 and below.
  • CMS nanocarriers efficiently loaded and transported Nile red (NR) in supramolecular aggregates and doxorubicin (DOX) in a unimolecular fashion.
  • DOX-loaded pH-CMS nanocarriers demonstrated significantly higher cytotoxicity compared to stable CMS nanocarriers after cellular uptake.
  • Enhanced drug release from pH-CMS nanocarriers was attributed to the cleavage of the pH-labile imine bond within intracellular compartments.

Conclusions:

  • The novel pH-responsive CMS nanocarriers are effective for targeted delivery of anticancer drugs like doxorubicin.
  • The pH-labile imine linker facilitates controlled drug release in acidic tumor microenvironments or intracellular compartments.
  • These pH-CMS nanocarriers represent a promising platform for enhancing the therapeutic index of chemotherapy by improving drug targeting and reducing systemic toxicity.