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Arginine‐Modified Nanostructured Lipid Carriers with Charge‐Reversal and pH‐Sensitive Membranolytic Properties for Anticancer Drug Delivery
Author(s) -
Sun Minjie,
Li Jing,
Zhang Cuiting,
Xie Ying,
Qiao Hongzhi,
Su Zhigui,
Oupický David,
Ping Qineng
Publication year - 2017
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201600693
Subject(s) - nanocarriers , endocytosis , arginine , drug delivery , in vivo , chitosan , surface charge , drug carrier , zeta potential , pharmacology , biophysics , drug , liposome , in vitro , chemistry , materials science , nanoparticle , biochemistry , nanotechnology , cell , medicine , biology , amino acid , microbiology and biotechnology
The ability to escape endo/lysosomal trafficking is critically important to prevent entrapment of nanomedicines in lysosomes and to achieve maximum therapeutic efficacy of drugs delivered to cells through endocytosis. In this study, a novel pH‐sensitive chitosan carrier with the ability to reverse its charge during endo/lysosomal trafficking is developed as a way of improving lysosomal disruption. N ‐Arginine‐ N ‐octyl chitosan (AOCS) is synthesized by grafting l ‐arginine onto carboxymethyl chitosan. The AOCS is used to modify the surface of nanostructured lipid carriers (NLC) to prepare pH‐sensitive charge‐reversal lysosomolytic nanocarriers (ANLC). The ANLC is loaded with 10‐hydroxycamptothecin (HCPT). The results show that ANLC is able to reverse surface zeta potential from negative to positive at lysosomal pH, which contributes to improved release of encapsulated drugs into cytoplasm. The lysosomolytic capability of ANLC is confirmed by confocal microscopy and transmission electron microscopy. In vitro studies demonstrate that the anticancer activity of HCPT‐loaded ANLC is improved when compared with HCPT‐NLC and free HCPT. In vivo pharmacokinetics and tissue distribution analysis show improved delivery of HCPT‐ANLC to subcutaneous Heps mouse liver tumors and greatly improved antitumor activity. The results present ANLC as a promising drug delivery carrier for improved antitumor therapy.