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Polymeric carriers enhance targeted drug delivery by increasing efficacy while minimizing off-target effects. These carriers comprise a biodegradable polymeric backbone integrated with functional elements that enable targeting, improve physicochemical properties, and regulate drug release.Targeting MechanismsThe targeting ability of polymeric carriers is mediated by a homing device, which is a molecular recognition component designed to selectively bind to specific tissues or cells. Monoclonal...

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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cell Biology

Background:

  • Cytosolic delivery of therapeutic agents is crucial for enhancing efficacy.
  • Single-chain polymer nanoparticles (SCNPs) are promising nanocarriers (5-20 nm) but face challenges in cytosolic delivery.
  • Targeting specific organelles requires precise control over nanoparticle intracellular fate.

Purpose of the Study:

  • To synthesize and functionalize active ester-SCNPs for controlled intracellular targeting.
  • To investigate the impact of surface charge modification on SCNP cellular uptake and localization.
  • To develop a strategy for directing SCNPs to the cytosol for improved biomedical applications.

Main Methods:

  • Synthesis of ~10 nm active ester-SCNPs via intramolecular thiol-Michael addition cross-linking.
  • Functionalization of SCNPs with varying amounts of tertiary amines (0-60 mol%) to tune surface charge.
  • Assessment of cytotoxicity in bEND.3 cells.
  • Analysis of cellular uptake and intracellular localization using confocal microscopy.

Main Results:

  • SCNPs were successfully synthesized and functionalized with tunable positive surface charges.
  • No significant cytotoxicity was observed except at high concentrations and prolonged incubation.
  • SCNPs with high surface charges (45%, 60% amine functionalization) were delivered to the cytosol.
  • SCNPs with low surface charges (0-30% amine functionalization) were localized in lysosomes.

Conclusions:

  • Controlled surface modification of SCNPs can direct their intracellular localization.
  • High surface charge promotes cytosolic delivery, while low surface charge leads to lysosomal accumulation.
  • This strategy offers a pathway to enhance intracellular targeting for therapeutic applications.