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Changeable net charge on nanoparticles facilitates intratumor accumulation and penetration.
- Source :
-
Journal of Controlled Release . Jun2022, Vol. 346, p392-404. 13p. - Publication Year :
- 2022
-
Abstract
- The Enhanced Permeability and Retention (EPR) effect is a golden strategy for the nanoparticle (NP)-based targeting of solid tumors, and the surface property of NPs might be a determinant on their targeting efficiency. Poly(ethylene glycol) (PEG) is commonly used as a shell material; however, it has been pointed out that PEG-coated NPs may exhibit accumulation near tumor vasculature rather than having homogenous intratumor distribution. The PEG shell plays a pivotal role on prolonged blood circulation of NPs but potentially impairs the intratumor retention of NPs. In this study, we report on a shell material to enhance tumor-targeted delivery of NPs by maximizing the EPR effect: polyzwitterion based on ethylenediamine-based carboxybetaine [PGlu(DET-Car)], which shows the changeable net charge responding to surrounding pH. The net charge of PGlu(DET-Car), is neutral at physiological pH 7.4, allowing it to exhibit a stealth property during the blood circulation; however, it becomes cationic for tissue-interactive performance under tumorous acidic conditions owing to the stepwise protonation behavior of ethylenediamine. Indeed, the PGlu(DET-Car)-coated NPs (i.e. , gold NPs in the present study) exhibited prolonged blood circulation and remarkably enhanced tumor accumulation and retention than PEG-coated NPs, achieving 32.1% of injected dose/g of tissue, which was 4.2 times larger relative to PEG-coated NPs. Interestingly, a considerable portion of PGlu(DET-Car)-coated NPs clearly penetrated into deeper tumor sites and realized the effective accumulation in hypoxic regions, probably because the cationic net charge of PGlu(DET-Car) is augmented in more acidic hypoxic regions. This study suggests that the changeable net charge on the NP surface in response to tumorous acidic conditions is a promising strategy for tumor-targeted delivery based on the EPR effect. [Display omitted] • Nanoparticles can enter tumor tissues through EPR effect. • PGlu(DET-Car) is a polyzwitterion which becomes cationic at tumorous pH. • PGlu(DET-Car)-coated nanoparticles achieves the effective tumor delivery. • Such pH-responsive design has comparable (or higher) stealthiness relative to PEG. • The coated nanoparticle penetrates into deeper tumor sites such as hypoxic areas. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01683659
- Volume :
- 346
- Database :
- Academic Search Index
- Journal :
- Journal of Controlled Release
- Publication Type :
- Academic Journal
- Accession number :
- 157455275
- Full Text :
- https://doi.org/10.1016/j.jconrel.2022.04.025