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Related Concept Videos

Lysosomal Hydrolases01:22

Lysosomal Hydrolases

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Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
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Assessing Autophagic Flux by Measuring LC3, p62, and LAMP1 Co-localization Using Multispectral Imaging Flow Cytometry
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Liposomal Formulation of Hydroxychloroquine Can Inhibit Autophagy In Vivo.

Wieslawa H Dragowska1, Jagbir Singh1,2, Mohamed Wehbe1,3

  • 1Department of Experimental Therapeutics, BC Cancer, Vancouver, BC V5Z 1L3, Canada.

Pharmaceutics
|January 25, 2025
PubMed
Summary
This summary is machine-generated.

Liposomal hydroxychloroquine (HCQ) enhanced autophagy inhibition in preclinical cancer models. However, this did not improve therapeutic outcomes when combined with gefitinib for resistant breast cancer.

Keywords:
autophagybreast cancergefitinibhydroxychloroquineliposomes

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Area of Science:

  • Oncology
  • Pharmacology
  • Cancer Biology

Background:

  • Hydroxychloroquine (HCQ) impairs autophagy, enhancing anti-cancer therapy in preclinical studies.
  • Achieving effective in vivo HCQ concentrations at tumor sites is challenging.
  • Previous research showed free HCQ combined with gefitinib reduced tumor volume in gefitinib-resistant breast cancer xenografts.

Purpose of the Study:

  • To evaluate if liposomal HCQ can modulate autophagy in vivo.
  • To assess if liposomal HCQ augments treatment outcomes in a gefitinib-resistant breast cancer model.

Main Methods:

  • Developed pH-loaded and copper-complexed liposomal HCQ formulations.
  • Evaluated pharmacokinetics in CD1 mice and efficacy in immunocompromised mice with JIMT-1 xenografts.
  • Assessed autophagy markers (LC3-II, p62) in tumor tissue via Western blot.

Main Results:

  • Liposomal HCQ formulations increased total drug exposure ~850-fold compared to free HCQ.
  • Both liposomal and free HCQ with gefitinib showed comparable therapeutic benefits.
  • Liposomal HCQ combination showed enhanced in vivo autophagy inhibition (increased LC3-II and p62) versus free HCQ.

Conclusions:

  • Liposomal HCQ demonstrates greater in vivo autophagy modulation potential than free HCQ.
  • This enhanced autophagy inhibition did not translate to improved therapeutic effects in this gefitinib-resistant model.