Hyaluronic Acid-Modified Cationic Lipid–PLGA Hybrid Nanoparticles as a Nanovaccine Induce Robust Humoral and Cellular Immune Responses

Abstract

Here, we investigated the use of hyaluronic acid (HA)-decorated cationic lipid-poly(lactide-co-glycolide) acid (PLGA) hybrid nanoparticles (HA-DOTAP-PLGA NPs) as vaccine delivery vehicles, which were originally developed for the cytosolic delivery of genes. Our results demonstrated that after the NPs uptake by dendritic cells (DCs), some of the antigens that were encapsulated in HA-DOTAP-PLGA NPs escaped to the cytosolic compartment, and whereas some of the antigens remained in the endosomal/lysosomal compartment, where both MHC-I and MHC-II antigen presentation occurred. Moreover, HA-DOTAP-PLGA NPs led to the up-regulation of MHC, costimulatory molecules, and cytokines. In vivo experiments further revealed that more powerful immune responses were induced from mice immunized with HA-DOTAP-PLGA NPs when compared with cationic lipid-PLGA nanoparticles and free ovalbumin (OVA); the responses included antigen-specific CD4(+) and CD8(+) T-cell responses, the production of antigen-specific IgG antibodies and the generation of memory CD4(+) and CD8(+) T cells. Overall, these data demonstrate the high potential of HA-DOTAP-PLGA NPs for use as vaccine delivery vehicles to elevate cellular and humoral immune responses.

<p>Hyaluronic Acid Capped, Irinotecan and Gene Co-Loaded Lipid-Polymer Hybrid Nanocarrier-Based Combination Therapy Platform for Colorectal Cancer</p>

“…HA modified nanoparticles have been widely used for the delivery of drugs and genes for tumor targeting. [32][33][34] They were expected to accumulate in cancer tissues as a combined function of the magnetic targeting-enhanced EPR effect and HA-mediated active targeting after intravenous injection. 35 Particle sizes smaller than 200 nm are conducive to drug accumulation at the tumor site based on the EPR effect, thereby reducing the drug dose and minimizing toxicity.…”

Synergy effects of Polyinosinic-polycytidylic acid, CpG oligodeoxynucleotide, and cationic peptides to adjuvant HPV E7 epitope vaccine through preventive and therapeutic immunization in a TC-1 grafted mouse model

“…2, PBS and DOTAP-CpG-Poly I:C-Cramp groups vs Ag and DOTAP-Cramp-Ag groups, P<0.01). 38,39 These memory cells were also more numerous in the Poly I:C-adjuvanted groups (although no significant differences were detected between the Ag and DOTAP-Cramp-Ag groups vs the DOTAP-Poly I:C-Ag and DOTAP-Poly I:C-Cramp-Ag groups, P>0.05) and peaked in the CpG-adjuvanted groups (compared to groups without CpG, P<0.05) (Fig. 2).…”

Niclosamide encapsulated polymeric nanocarriers for targeted cancer therapy

“…It was noticed that the layer of HA has raised the surface charge to more negative when compared to that of uncoated (NIC-PLGA NP), which is likely attributed with its negative surface charge. 45 The prepared [(NIC-PLGA NP)HA] nanodispersion were found to exhibit a hydrodynamic diameter of 201.8 AE 3.6 nm with a PDI value of 0.164 conrming the monodispersed of the prepared dispersion (ESI Fig. S2 †).…”