Programmable nanocarriers with reversible ligand shielding and acid-triggered burst release for sequential tumor...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Solid tumor treatment with nanomedicines is limited by poor tumor penetration and slow intracellular drug release.
• These delivery challenges result in suboptimal therapeutic efficacy for many nanomedicine-based cancer therapies.

Purpose of the Study:

• To design and construct a programmable nanomedicine (sDPFP NMs) that overcomes poor tumor penetration and intracellular delivery limitations.
• To achieve enhanced tumor penetration via hypoxia-regulated reversible ligand shielding.
• To enable rapid intracellular drug release through acid-triggered self-amplifying degradation.

Main Methods:

• Developed a nanomedicine (sDPFP NMs) with a hydrophobically modified dextran (sDex) core and polyethylene glycol (PEG) shell.
• Incorporated a hypoxia-responsive azobenzene linker for reversible folate ligand shielding.
• Utilized acid-sensitive self-amplifying degradation of sDex for triggered drug release.

Main Results:

• sDPFP NMs demonstrated enhanced penetration into solid tumor tissues.
• Acidic conditions within tumor cells triggered rapid burst release of the encapsulated drug (doxorubicin).
• The nanomedicine exhibited significant anti-tumor efficacy, overcoming delivery bottlenecks.

Conclusions:

• The developed sDPFP NMs offer a promising new strategy for solid tumor therapy.
• Reversible ligand shielding and acid-triggered burst release effectively enhance nanomedicine performance.
• This approach addresses critical challenges in tumor penetration and intracellular drug delivery.