DNA vaccination for cervical cancer; a novel technology platform of RALA mediated gene delivery via polymeric microneedles

被引：105

作者：

Ali, Ahlam A. ^{[1
]}

McCrudden, Cian M. ^{[1
]}

McCaffrey, Joanne ^{[1
]}

McBride, John W. ^{[1
]}

Cole, Grace ^{[1
]}

Dunne, Nicholas J. ^{[2
]}

Robson, Tracy ^{[3
]}

Kissenpfennig, Adrien ^{[4
]}

Donnelly, Ryan F. ^{[1
]}

McCarthy, Helen O. ^{[1
]}

机构：

[1] Queens Univ Belfast, Sch Pharm, Belfast BT9 7BL, Antrim, North Ireland

[2] Dublin City Univ, Sch Mech & Mfg Engn, Dublin, Ireland

[3] Royal Coll Surgeons Ireland, Mol & Cellular Therapeut, Dublin 2, Ireland

[4] Queens Univ Belfast, Ctr Infect & Immun, Wellcome Wolfson Inst Expt Med, Belfast, Antrim, North Ireland

来源：

NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE | 2017年 / 13卷 / 03期

关键词：

DNA vaccination; Microneedles; RALA peptide; Cervical cancer; HUMAN-PAPILLOMAVIRUS; ENHANCED IMMUNOGENICITY; PROTEIN DELIVERY; VACCINES; CELL; NANOPARTICLES; ARRAYS; MECHANISMS; ANTITUMOR; RESPONSES;

D O I：

10.1016/j.nano.2016.11.019

中图分类号：

TB3 [工程材料学];

学科分类号：

0805 ; 080502 ;

摘要：

HPV subtypes (16, 18) are associated with the development of cervical cancer, with oncoproteins E6 and E7 responsible for pathogenesis. The goal of this study was to evaluate our 'smart system' technology platform for DNA vaccination against cervical cancer. The vaccination platform brings together two main components; a peptide RALA which condenses DNA into cationic nanoparticles (NPs), and a polymeric polyvinylpyrrolidone (PVP) microneedle (MN) patch for cutaneous delivery of the loaded NPs. RALA condensed E6/E7 DNA into NPs not exceeding 100 nm in diameter, and afforded the DNA protection from degradation in PVP. Sera from mice vaccinated with MN/RALA-E6/ E7 were richer in E6/E7-specific IgGs, displayed a greater T-cell-mediated TC-1 cytotoxicity and contained more IFN-gamma than sera from mice that received NPs intramuscularly. More importantly, MN/RALA-E6/E7 delayed TC-1 tumor initiation in a prophylactic model, and slowed tumor growth in a therapeutic model of vaccination, and was more potent than intramuscular vaccination. (C) 2016 Elsevier Inc. All rights reserved.

引用

页码：921 / 932

页数：12

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