Small molecule delivery to solid tumors with chitosan-coated PLGA particles: A lesson learned from comparative...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery

Background:

• Polymeric nanoparticles (NPs) aim to improve tumor drug delivery over free solutions.
• Traditional polyethylene glycol (PEG) coatings can hinder NP-cell interactions in tumors.
• Developing alternative surface coatings is crucial for enhanced NP efficacy.

Purpose of the Study:

• To investigate zwitterionic chitosan (ZWC) as a surface coating for poly(lactic-co-glycolic acid) (PLGA) NPs.
• To evaluate the in vivo tumor delivery and retention of ZWC-coated NPs compared to PEG-coated NPs.
• To assess the impact of NP surface modification on drug release and tumor distribution.

Main Methods:

• Synthesized ZWC-coated PLGA NPs and characterized their pH-dependent surface charge and cellular interactions.
• Utilized in vivo magnetic resonance (MR) imaging and fluorescence whole-body imaging in mice bearing LS174T-xenografts.
• Tracked iron oxide particles and indocyanine green (ICG) encapsulated within NPs as tracers.

Main Results:

• ZWC-coated NPs exhibited pH-dependent surface charge and differential cellular interactions.
• MR imaging demonstrated increased NP persistence in tumors for ZWC-coated NPs compared to PEG-coated NPs.
• Fluorescence imaging revealed that enhanced NP retention did not significantly improve ICG distribution due to rapid dye release.

Conclusions:

• Zwitterionic chitosan (ZWC) coating can improve nanoparticle (NP) retention within tumors.
• Effective drug delivery from NPs relies on stable drug retention during circulation.
• Surface-engineered NPs require optimized drug loading and release profiles for successful therapeutic translation.