Abstract
Current clinical applications of protein therapy are largely limited to systemically accessible targets in vascular or extracellular areas. Major obstacles to the widespread application of protein therapeutics in cancer treatment include low membrane permeability and endosomal entrapment. Herein, we report a multistage nanoparticle (NP) strategy for systemic and cytosolic protein delivery to tumor cells, by encapsulating a protein conjugate, tetra-guanidinium (TG)-modified saporin, into tumor microenvironment (TME) pH-responsive polymeric NPs. Upon reaching the tumor site after systemic circulation, the polymeric NPs respond rapidly to the acidic tumor microenvironment and release the TG-saporin conjugates, which penetrate the tumor tissue and enter into tumor cells via TG-mediated cytosolic transportation. The TG-saproin NPs showed potent inhibition of lung cancer cell growth in vitro and in vivo. We expect that this multistage NP delivery strategy with long blood circulation, deep tumor penetration, and efficient cytosolic transport may be applicable to various therapeutic proteins for effective cancer treatment.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
