Silk-elastinlike protein polymer hydrogels for localized adenoviral gene therapy of head and neck tumors

Area of Science:

• Biotechnology
• Biomaterials Science
• Oncology

Background:

• Gene therapy faces challenges with vector dissemination, transient expression, and rapid clearance.
• Adenoviral vectors are promising for gene therapy but require improved delivery methods.

Purpose of the Study:

• To investigate the impact of silk-elastinlike protein polymer (SELP) hydrogels on adenoviral vector biodistribution and anticancer efficacy.
• To evaluate SELP hydrogels as a localized delivery system for head and neck cancer gene therapy.

Main Methods:

• Adenovirus carrying reporter genes (Ad-LacZ, Ad-Luc) and therapeutic gene (Ad-Tk) were evaluated in (nu/nu) mice with head and neck cancer.
• SELP hydrogel concentrations were varied to assess their effect on viral gene expression and biodistribution.
• Antitumor efficacy was assessed using the Ad-Tk and ganciclovir (GSV) combination therapy within SELP hydrogels.

Main Results:

• SELP (4 wt %) hydrogels localized viral release and minimized dissemination to the liver.
• Reporter gene expression was enhanced by 4-8 fold in SELP matrices compared to virus alone.
• The combination of SELP-Ad-Tk with GSV significantly reduced tumor volume compared to virus alone.

Conclusions:

• SELP hydrogels offer temporal and spatial control for adenoviral gene delivery to head and neck tumors.
• SELP hydrogels represent a promising strategy to overcome key obstacles in adenoviral gene therapy.
• This approach enhances therapeutic efficacy and minimizes off-target effects for cancer treatment.