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pH-Responsive Hybrid Nanoassemblies for Cancer Treatment: Formulation Development, Optimization, and In Vitro

Patrícia V Teixeira1,2, Filomena Adega3,4, Paula Martins-Lopes2,4

  • 1CF-UM-UP-Centro de Física das Universidades do Minho e Porto, Departamento de Física, Universidade do Minho, 4710-057 Braga, Portugal.

Pharmaceutics
|February 25, 2023
PubMed
Summary

Intelligent pH-triggered drug delivery nanoassemblies loaded with doxorubicin (DOX) show targeted release in acidic cancer environments, reducing healthy cell toxicity. These hybrid nanoassemblies offer high drug loading and efficacy against cancer cells.

Keywords:
cancerchemotherapeutic agentsdoxorubicindrug-delivery systemslyotropic nonlamellar liquid crystalline nanoassemblies

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Area of Science:

  • Biomaterials Science
  • Nanotechnology
  • Cancer Therapeutics

Background:

  • Current cancer drug delivery faces challenges with efficacy and specificity.
  • Intelligent materials responding to environmental stimuli are needed for improved drug carriers.
  • Acidic tumor microenvironments and endosomal vesicles present opportunities for targeted drug release.

Purpose of the Study:

  • To develop and optimize pH-triggered drug delivery nanoassemblies for enhanced cancer therapy.
  • To investigate the controlled release of doxorubicin (DOX) from nanoassemblies at different pH levels.
  • To evaluate the efficacy and cytotoxicity of DOX-loaded nanoassemblies in cancer models.

Main Methods:

  • Fabrication and characterization of hybrid (polymeric/lipid) lyotropic non-lamellar liquid crystalline (LNLCs) nanoassemblies.
  • Assessment of DOX encapsulation efficiency, drug loading content, and colloidal stability.
  • In vitro evaluation of DOX release profiles at physiological (pH 7.5) and acidic (pH 5.5) conditions.
  • Confocal microscopy to study cellular uptake and intracellular localization in hepatocellular carcinoma cells.
  • Cytotoxicity assays on various cancer cell lines (MDA-MB 231, HepG2, NCI-H1299) and a normal cell line.

Main Results:

  • LNLCs demonstrated high DOX encapsulation (>90%) and drug loading (>7%) with stability for over 4 weeks.
  • Significantly increased DOX release at pH 5.5 compared to pH 7.5, indicating pH-triggered release.
  • Confocal microscopy confirmed cellular uptake and nuclear proximity of DOX-loaded LNLCs, inducing apoptosis.
  • DOX-loaded LNLCs exhibited higher cytotoxicity against cancer cell lines than free DOX.
  • Free DOX showed higher cytotoxicity in normal cells compared to DOX-loaded LNLCs at 24 h.

Conclusions:

  • pH-triggered DOX-loaded LNLCs offer a promising strategy for targeted cancer therapy.
  • The hybrid nanoassemblies show potential for reduced systemic toxicity due to targeted drug release.
  • These findings support further exploration of LNLCs as intelligent drug delivery systems for cancer treatment.