Albumin nanocapsules and nanocrystals for efficient intracellular drug release.
Sharafudheen Pottanam ChaliJaana WestmeierFranziska KrebsShuai JiangFriederike Pauline NeesenDoğa UncuerMario SchelhaasStephan GrabbeChristian BeckerKatharina LandfesterKerstin SteinbrinkPublished in: Nanoscale horizons (2024)
In order to achieve a therapeutic effect, many drugs have to reach specific cellular compartments. Nanoscale drug delivery systems extend the circulation time, reduce adverse effects and thus improve tolerability compared to systemic administration. We have developed two types of albumin-coated nanocarriers equipped with built-in dyes to track their cellular uptake and intracellular enzymatic opening. Using the approved antiprotozoal drug and STAT3 inhibitor Atovaquone (Ato) as prototype for a hydrophobic small molecule, we show that Ato-loaded ovalbumin-coated nanocapsules (Ato-nCap) preferentially enter human myeloid cells. In contrast, Ato nanocrystals coated with human serum albumin (Ato-nCry) distribute their cargo in all different immune cell types, including T and B cells. By measuring the effect of Ato nanocarriers on induced STAT3 phosphorylation in IL-10-primed human dendritic cells and constitutive STAT3 phosphorylation in human melanoma cells, we demonstrate that the intracellular Ato release is particularly effective from Ato nanocrystals and less toxic than equal doses of free drug. These new nanocarriers thus represent effective systems for intracellular drug delivery.
Keyphrases
- drug delivery
- drug release
- endothelial cells
- dendritic cells
- cancer therapy
- small molecule
- pluripotent stem cells
- cell proliferation
- high glucose
- reactive oxygen species
- human serum albumin
- room temperature
- oxidative stress
- acute myeloid leukemia
- induced apoptosis
- magnetic resonance imaging
- clinical trial
- open label
- energy transfer
- computed tomography
- bone marrow
- cell death
- randomized controlled trial
- signaling pathway
- emergency department
- ionic liquid
- diabetic rats
- hydrogen peroxide
- endoplasmic reticulum stress
- cell cycle arrest
- electronic health record
- wound healing
- high speed
- atomic force microscopy