Multistage Systemic and Cytosolic Protein Delivery for Effective Cancer Treatment

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Protein therapeutics face limitations in cancer treatment due to poor cell membrane permeability and endosomal entrapment.
• Current applications are restricted to targets accessible in vascular or extracellular areas.

Purpose of the Study:

• To develop a multistage nanoparticle (NP) strategy for systemic and cytosolic protein delivery to tumor cells.
• To overcome delivery barriers for enhanced cancer therapy.

Main Methods:

• Encapsulation of tetra-guanidinium (TG)-modified saporin protein conjugates into pH-responsive polymeric NPs.
• Systemic administration and utilization of the acidic tumor microenvironment (TME) for NP triggered release.
• TG-mediated cytosolic transport into tumor cells.

Main Results:

• The TG-saporin NPs demonstrated potent inhibition of lung cancer cell growth in vitro.
• Effective inhibition of lung cancer growth was also observed in vivo.
• The NPs exhibited long blood circulation, deep tumor penetration, and efficient cytosolic transport.

Conclusions:

• The developed multistage NP delivery strategy facilitates efficient cytosolic protein delivery to tumor cells.
• This approach holds promise for various therapeutic proteins in effective cancer treatment.
• The strategy addresses critical challenges in protein therapeutics for oncology.