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Multistage Systemic and Cytosolic Protein Delivery for Effective Cancer Treatment.
- Source :
-
Nano letters [Nano Lett] 2022 Jan 12; Vol. 22 (1), pp. 111-118. Date of Electronic Publication: 2021 Dec 28. - Publication Year :
- 2022
-
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.
Details
- Language :
- English
- ISSN :
- 1530-6992
- Volume :
- 22
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nano letters
- Publication Type :
- Academic Journal
- Accession number :
- 34962818
- Full Text :
- https://doi.org/10.1021/acs.nanolett.1c03293