Rationalizing the use of functionalized poly-lactic-co-glycolic acid nanoparticles for dendritic cell-based targeted anticancer therapy.

Background: Delivery of PLGA (poly [D, L-lactide-co-glycolide])-based biodegradable nanoparticles (NPs) to antigen presenting cells, particularly dendritic cells, has potential for cancer immunotherapy.

Materials & Methods: Using a PLGA NP vaccine construct CpG-NP-Tag (CpG-ODN-coated tumor antigen [Tag] encapsulating NP) prepared using solvent evaporation technique we tested the efficacy of ex vivo and in vivo use of this construct as a feasible platform for immune-based therapy.

Results: CpG-NP-Tag NPs were avidly endocytosed and localized in the endosomal compartment of bone marrow-derived dendritic cells.

Enhancement of anti-tumor effect of particulate vaccine delivery system by 'bacteriomimetic' CpG functionalization of poly-lactic-co-glycolic acid nanoparticles.

Aim: Low immunogenicity remains a major obstacle in realizing the full potential of cancer vaccines. In this study, we evaluated CpG-coated tumor antigen (Tag)-encapsulating 'bacteriomimetic' nanoparticles (CpG-nanoparticle [NP]-Tag NPs) as an approach to enhance anti-tumor immunity.

Materials & Methods: CpG-NP-Tag NPs were synthesized, characterized for their physicochemical properties and tested in vivo.

Inhibition of mercapturic acid pathway-mediated disposal of 4-hydroxynonenal causes complete and sustained remission of human cancer xenografts in nude mice.

Environmental electrophilic chemical carcinogens are detoxified via mercapturic acid pathway to be excreted as mercapturic acid derivatives. Mercapturic acid pathway is also involved in the metabolism of pro-apoptotic and toxic endogenous electrophiles such as 4-hydroxynonenal (HNE). HNE is a common denominator in stress induced signaling and is a pro-apoptotic second messenger that affects cell cycle signaling in a concentration dependent manner.