Arginine‐Modified Nanostructured Lipid Carriers with Charge‐Reversal and pH‐Sensitive Membranolytic Properties for Anticancer Drug Delivery. Issue 8 (10th February 2017)

• Record Type: Journal Article
• Authors: Sun, Minjie; Li, Jing; Zhang, Cuiting; Xie, Ying; Qiao, Hongzhi; Su, Zhigui; Oupický, David; Ping, Qineng
• Is Part Of: Advanced healthcare materials. Volume 6:Issue 8(2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-02-10
• Subjects: charge‐reversal -- lysosomal disruptive -- nanolipid carriers -- pH‐sensitive; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1002/adhm.201600693
• Languages: English
• ISSNs: 2192-2640

Abstract

Abstract : 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 graftingl ‐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. Abstract : pH‐sensitive charge‐reversal lysosomolytic nanocarriers (ANLC) are prepared by modified N ‐arginine‐ N ‐octyl chitosan onto the surface of nanostructured lipid carriers. The ANLC is loaded with 10‐hydroxycamptothecin. 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, and greatly improved antitumor activity.