Ionically crosslinked Ad/chitosan nanocomplexes processed by electrospinning for targeted cancer gene therapy

Area of Science:

• Biotechnology
• Gene Therapy
• Nanomedicine

Background:

• Systemic administration of tumor-targeting adenoviral (Ad) complexes is crucial for effective cancer gene therapy, impacting both primary and metastatic tumors.
• Targeted delivery systems are needed to enhance Ad transduction efficiency and minimize off-target effects and immune reactions.

Purpose of the Study:

• To develop and characterize novel Ad/chitosan-PEG-FA nanocomplexes for enhanced, tumor-specific adenoviral gene delivery.
• To evaluate the targeting efficiency, transduction capability, and immunomodulatory effects of the developed nanocomplexes.

Main Methods:

• Electrospinning was employed to create Ad/chitosan-PEG-FA nanocomplexes.
• Characterization included NMR, FT-IR, dynamic light scattering, zeta potentiometry, and electron microscopy.
• In vitro transduction efficiency was assessed in FA receptor-positive (KB) and negative (U343) cells, and IL-6 production from macrophages was measured.

Main Results:

• Ad/chitosan-PEG-FA nanocomplexes were successfully synthesized with an average size of ~140 nm and a surface charge of 2.1 mV.
• Nanocomplexes showed good dispersion, stability, and retained Ad biological activity.
• FA-targeted transduction was confirmed in KB cells, with a 57.2% increase in efficiency compared to Ad/chitosan, and reduced IL-6 production from macrophages.

Conclusions:

• Ad/chitosan-PEG-FA nanocomplexes facilitate effective, FA receptor-mediated tumor-specific adenoviral transduction.
• The developed system demonstrates potential for treating metastatic cancers via systemic administration due to enhanced targeting and reduced immune response.