Arginine-Modified Nanostructured Lipid Carriers with Charge-Reversal and pH-Sensitive Membranolytic Properties for Anticancer Drug Delivery

Minjie Sun, Jing Li, Cuiting Zhang, Ying Xie, Hongzhi Qiao, Zhigui Su, David Oupicky, Qineng Ping

Research output: Contribution to journalArticle

9 Citations (Scopus)

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 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.

Original languageEnglish (US)
Article number1600693
JournalAdvanced healthcare materials
Volume6
Issue number8
DOIs
StatePublished - Apr 19 2017

Fingerprint

Arginine
Drug delivery
Chitosan
Lipids
Medical nanotechnology
Pharmacokinetics
Confocal microscopy
Zeta potential
Pharmaceutical Preparations
Liver
Nanomedicine
Tumors
Drug Carriers
Tissue Distribution
Tissue
Endocytosis
Lysosomes
Transmission electron microscopy
Transmission Electron Microscopy
Confocal Microscopy

Keywords

  • charge-reversal
  • lysosomal disruptive
  • nanolipid carriers
  • pH-sensitive

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering
  • Pharmaceutical Science

Cite this

Arginine-Modified Nanostructured Lipid Carriers with Charge-Reversal and pH-Sensitive Membranolytic Properties for Anticancer Drug Delivery. / Sun, Minjie; Li, Jing; Zhang, Cuiting; Xie, Ying; Qiao, Hongzhi; Su, Zhigui; Oupicky, David; Ping, Qineng.

In: Advanced healthcare materials, Vol. 6, No. 8, 1600693, 19.04.2017.

Research output: Contribution to journalArticle

Sun, Minjie ; Li, Jing ; Zhang, Cuiting ; Xie, Ying ; Qiao, Hongzhi ; Su, Zhigui ; Oupicky, David ; Ping, Qineng. / Arginine-Modified Nanostructured Lipid Carriers with Charge-Reversal and pH-Sensitive Membranolytic Properties for Anticancer Drug Delivery. In: Advanced healthcare materials. 2017 ; Vol. 6, No. 8.
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