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A polymeric nanocarrier with a tumor acidity-activatable arginine-rich (R 9 ) peptide for enhanced drug delivery.
- Source :
-
Biomaterials science [Biomater Sci] 2020 Apr 15; Vol. 8 (8), pp. 2255-2263. - Publication Year :
- 2020
-
Abstract
- Cell-penetrating peptides (CPPs) have been considered as a powerful tool to improve the intracellular and nuclear delivery efficiency of nanocarriers. However, their clinical application is limited because of their nonspecific targeting function, short half-life, and severe system toxicity. Herein, we have developed a polymeric nanocarrier with a tumor acidity-activatable arginine-rich (R9) peptide for targeted drug delivery. The nanocarrier is fabricated with a R9-conjugated amphiphilic diblock polymer of poly(ethylene glycol) (PEG) and poly(hexyl ethylene phosphate) (PHEP), and then further coated with tumor acidity-activatable polyanionic polyphosphoester through electrostatic interaction in order to block the nonspecific targeting function of the R9 peptide. In the slightly acidic tumor extracellular environment (∼pH 6.5), tumor acidity-activatable polyanionic polyphosphoester would be deshielded from the nanoparticles, resulting in the re-exposure of the R9 peptide to enhance tumor cellular uptake. As a result, intracellular concentration of payload in 4T1 tumor cells significantly increased at pH 6.5. And, we further demonstrate that such a delivery system remarkably promoted the anti-tumor efficiency of chemotherapeutic drugs in tumor-bearing mice, offering great potential for drug delivery and cancer therapy.
- Subjects :
- Animals
Antibiotics, Antineoplastic chemistry
Antibiotics, Antineoplastic pharmacokinetics
Cell Line, Tumor
Cell Survival drug effects
Doxorubicin chemistry
Doxorubicin pharmacokinetics
Drug Carriers chemistry
Drug Carriers pharmacokinetics
Female
Hydrogen-Ion Concentration
Mammary Neoplasms, Experimental chemistry
Mammary Neoplasms, Experimental metabolism
Mammary Neoplasms, Experimental pathology
Mice, Inbred BALB C
Nanoparticles chemistry
Polymers chemistry
Polymers pharmacokinetics
Static Electricity
Tumor Burden drug effects
Antibiotics, Antineoplastic administration & dosage
Doxorubicin administration & dosage
Drug Carriers administration & dosage
Mammary Neoplasms, Experimental drug therapy
Nanoparticles administration & dosage
Polymers administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 2047-4849
- Volume :
- 8
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Biomaterials science
- Publication Type :
- Academic Journal
- Accession number :
- 32129378
- Full Text :
- https://doi.org/10.1039/d0bm00069h