Targeting CDK4/6 in glioblastoma via in situ injection of a cellulose-based hydrogel

Area of Science:

• Biomaterials Science
• Nanotechnology
• Oncology

Background:

• Glioblastoma (GBM) remains a challenging brain tumor with poor prognosis despite aggressive treatments.
• Limited blood-brain barrier penetration restricts the efficacy of drugs like palbociclib (PB).

Purpose of the Study:

• To investigate a cellulose-based hydrogel for in situ brain delivery of palbociclib (PB) to treat glioblastoma (GBM).
• To evaluate the hydrogel's ability to enhance PB's anti-GBM effects via controlled release and reactive oxygen species (ROS) generation.

Main Methods:

• Palbociclib (PB) was encapsulated in a cellulose nanocrystal hydrogel crosslinked with polydopamine, Cu2+, and hexadecylamine (PB@PH/Cu-CNCs).
• The hydrogel demonstrated sustained drug release and acid-responsive de-polymerization.
• Cu2+ catalyzed a Fenton-like reaction, generating ROS enhanced by PB, inducing GBM cell senescence and apoptosis.

Main Results:

• PB@PH/Cu-CNCs showed sustained drug retention and controlled release in vivo.
• The combination of released Cu2+ and PB effectively induced GBM cell death.
• The hydrogel formulation exhibited superior anti-GBM efficacy compared to free PB or drug-free hydrogel in vitro and in an orthotopic glioma model.

Conclusions:

• In situ injection of PB-loaded hydrogel is an effective strategy for brain delivery of palbociclib.
• This approach enhances anti-GBM efficacy by leveraging Cu2+-mediated Fenton-like reactions for increased ROS production.