Proceedings of the National Academy of Sciences · 2004 · 229 citations · 31 references
EngineeringImmunologyGene DeliveryBiomedical EngineeringImmunotherapyNanomedicineCross-protectionConventional Microparticle FormulationsMicroparticle FormulationsCancer VaccinesVaccinologyCell-based Drug DeliveryVaccine DevelopmentNonviral Genetic VaccinesTherapeutic VaccinePolyvalent VaccineBiomolecular EngineeringVaccinationConventional FormulationsVaccine DesignMedicineVaccine Research
Nonviral genetic vaccines are less effective than viral vaccines, especially in cancer where weak epitopes and reduced antigen presentation limit immunity, and while microencapsulation protects DNA and targets APCs, conventional PLGA microparticles release payload too slowly and fail to elicit high gene expression. The study aims to develop a microparticle-based DNA delivery system using a degradable, pH‑sensitive poly‑β‑amino ester combined with PLGA. This system employs poly‑β‑amino ester/PLGA microparticles that rapidly release DNA in acidic environments, enhancing uptake by phagocytic antigen‑presenting cells. The formulations achieved 3–5 orders of magnitude higher transfection efficiency, strongly activated dendritic cells in vitro, and in vivo induced antigen‑specific rejection of syngeneic tumor cells, outperforming conventional microparticles.
Current nonviral genetic vaccine systems are less effective than viral vaccines, particularly in cancer systems where epitopes can be weakly immunogenic and antigen-presenting cell processing and presentation to T cells is down-regulated. A promising nonviral delivery method for genetic vaccines involves microencapsulation of antigen-encoding DNA, because such particles protect plasmid payloads and target them to phagocytic antigen-presenting cells. However, conventional microparticle formulations composed of poly lactic-co-glycolic acid take too long to release encapsulated payload and fail to induce high levels of target gene expression. Here, we describe a microparticle-based DNA delivery system composed of a degradable, pH-sensitive poly-beta amino ester and poly lactic-co-glycolic acid. These formulations generate an increase of 3-5 orders of magnitude in transfection efficiency and are potent activators of dendritic cells in vitro. When used as vaccines in vivo, these microparticle formulations, unlike conventional formulations, induce antigen-specific rejection of transplanted syngenic tumor cells.
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Proliferating dendritic cell progenitors in human blood.
Nikolaus Romani, Susanne Grüner, D Brang et al. · The Journal of Experimental Medicine · 1994 · 1.9K citations · Full text
Sanjeeb Kumar Sahoo, Jayanth Panyam, Swayam Prabha et al. · Journal of Controlled Release · 2002 · 958 citations
Engineering, Protein Nanoparticles, Polymer Nanotechnology +6