Characterization of poly(D,L-lactic-co-glycolic acid) based nanoparticulate system for enhanced delivery of antigens to dendritic cells

被引：188

作者：

Elamanchili, P ^{[1
]}

Diwan, M ^{[1
]}

Cao, M ^{[1
]}

Samuel, J ^{[1
]}

机构：

[1] Univ Alberta, Dent Pharm Ctr 3118, Fac Pharm & Pharmaceut Sci, Edmonton, AB T6G 2N8, Canada

来源：

VACCINE | 2004年 / 22卷 / 19期

关键词：

dendritic cells; vaccine delivery; nanospheres;

D O I：

10.1016/j.vaccine.2003.12.032

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Biodegradable nanoparticles made of poly(D,L-lactic acid-co-glycolic acid) (PLGA) copolymer were characterized for enhanced delivery of antigens to murine bone marrow derived dendritic cells (DCs) in vitro. PLGA nanoparticles were efficiently phagocytosed by the DCs (CD I I c, MHC class II+, CD86(+)) in culture, resulting in their intracellular localization. The efficiency of the uptake was influenced by the incubation time and nanoparticle concentration. DCs pulsed with PLGA nanoparticles containing an immunomodulator, monophosphoryl lipid A (MPLA), showed upregulation of surface expression of MHC class 11 and CD86 molecules. Delivery of a cancer-associated antigen (MUC1 mucin peptide: BLP25) and MPLA in PLGA nanoparticles was shown to be superior to their delivery in the soluble form for activation of naive T cells of normal and MUC1-transgenic mice. These results strongly suggest that PLGA nanoparticles provide an efficient vaccine delivery system for targeting DCs and the development of DC based cellular vaccines. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：2406 / 2412

页数：7

共 26 条

[1] Encapsulation of peptides in biodegradable microspheres prolongs their MHC class-I presentation by dendritic cells and macrophages in vitro [J].

Audran, R ;

Peter, K ;

Dannull, J ;

Men, Y ;

Scandella, E ;

Groettrup, M ;

Gander, B ;

Corradin, G .

VACCINE, 2003, 21 (11-12) :1250-1255

[2] Immunobiology of dendritic cells [J].

Banchereau, J ;

Briere, F ;

Caux, C ;

Davoust, J ;

Lebecque, S ;

Liu, YT ;

Pulendran, B ;

Palucka, K .

ANNUAL REVIEW OF IMMUNOLOGY, 2000, 18 :767-+

[3] Dendritic cells and the control of immunity [J].

Banchereau, J ;

Steinman, RM .

NATURE, 1998, 392 (6673) :245-252

[4] The role of dendritic cell subsets in selection between tolerance and immunity [J].

Belz, GT ;

Heath, WR ;

Carbone, FR .

IMMUNOLOGY AND CELL BIOLOGY, 2002, 80 (05) :463-468

[5] Biodegradable nanoparticle mediated antigen delivery to human cord blood derived dendritic cells for induction of primary T cell responses [J].

Diwan, M ;

Elamanchili, P ;

Lane, H ;

Gainer, A ;

Samuel, J .

JOURNAL OF DRUG TARGETING, 2004, 11 (8-10) :495-507

[6] Enhancement of immune responses by co-delivery of a CpG oligodeoxynucleotide and tetanus toxoid in biodegradable nanospheres [J].

Diwan, M ;

Tafaghodi, M ;

Samuel, J .

JOURNAL OF CONTROLLED RELEASE, 2002, 85 (1-3) :247-262

[7] Monophosphoryl lipid A activates both human dendritic cells and T cells [J].

Ismaili, J ;

Rennesson, J ;

Aksoy, E ;

Vekemans, J ;

Vincart, B ;

Amraoui, Z ;

Van Laethem, F ;

Goldman, M ;

Dubois, PM .

JOURNAL OF IMMUNOLOGY, 2002, 168 (02) :926-932

[8] A PHAGOSOME-TO-CYTOSOL PATHWAY FOR EXOGENOUS ANTIGENS PRESENTED ON MHC CLASS-I MOLECULES [J].

KOVACSOVICSBANKOWSKI, M ;

ROCK, KL .

SCIENCE, 1995, 267 (5195) :243-246

[9] Analysis of poly(D,L-lactic-co-glycolic acid) nanosphere uptake by human dendritic cells and macrophages in vitro [J].

Lutsiak, MEC ;

Robinson, DR ;

Coester, C ;

Kwon, GS ;

Samuel, J .

PHARMACEUTICAL RESEARCH, 2002, 19 (10) :1480-1487

[10] An advanced culture method for generating large quantities of highly pure dendritic cells from mouse bone marrow [J].

Lutz, MB ;

Kukutsch, N ;

Ogilvie, ALJ ;

Rössner, S ;

Koch, F ;

Romani, N ;

Schuler, G .

JOURNAL OF IMMUNOLOGICAL METHODS, 1999, 223 (01) :77-92

← 1 2 3 →