Potentiating Antigen Specific Immune Response by Targeted Delivery of the PLGA-Based Model Cancer Vaccine.

Targeted delivery of vaccine has the potential to localize the therapeutic agent to a target tissue with minimum side-effects. This article presents the development of a model targeted immunotherapeutic approach that will harness effective T cell response. Here, we investigated the impact of a model nanoparticulate cancer vaccine on the immune system of in vivo mice models. The nanoparticles (NPs) were prepared by a double emulsification solvent evaporation technique. The anti-CD205 targeted formulations were obtained either through physical adsorption or a covalent conjugation method. The structural integrity of ovalbumin (OV) was confirmed by circular dichroism spectroscopy. Flow cytometry and enzyme-linked immunosorbent assay experiments were performed to evaluate T cell proliferation and cytokine secretion. Our results indicate that the antigen-adjuvant combined formulation induced more powerful responses compared to formulations with either of these alone. Wild-type balb/c mice immunized with the targeted poly (D,L-lactic- co-glycolic-acid) (PLGA) NPs encapsulated with OV and monophosphoryl lipid A (MP) induced profound secretion of antigen-specific IgG antibodies and cytokines and generation of memory T cells. OV specific T cell receptor transgenic OT1 mice showed the highest production of cytotoxic T cells and increased the secretion of cytokines upon immunization with the targeted OVMP formulations. The enhanced response might be attributed to the OV depot effect at the subcutaneous site of injection that triggered effective induction of dendritic cells activation and helper T cell differentiation in the lymph nodes. Therefore, the developed targeted PLGA-based delivery system could be utilized as a successful model vaccine in the future.

Design and immunological evaluation of anti-CD205-tailored PLGA-based nanoparticulate cancer vaccine.

The aim of this research was to develop a targeted antigen-adjuvant assembled delivery system that will enable dendritic cells (DCs) to efficiently mature to recognize antigens released from tumor cells. It is important to target the DCs with greater efficiency to prime T cell immune responses. In brief, model antigen, ovalbumin (OV), and monophosphoryl lipid A adjuvant were encapsulated within the nanoparticle (NP) by double emulsification solvent evaporation method. Targeted NPs were obtained through ligand incorporation via physical adsorption or chemical conjugation process. Intracellular uptake of the NPs and the maturation of DCs were evaluated with flow cytometry. Remarkably, the developed delivery system had suitable physicochemical properties, such as particle size, surface charge, OV encapsulation efficiency, biphasic OV release pattern, and safety profile. The ligand modified formulations had higher targeting efficiency than the non-tailored NPs. This was also evident when the targeted formulations expressed comparatively higher fold increase in surface activation markers such as CD40, CD86, and major histocompatibility complex class II molecules. The maturation of DCs was further confirmed through secretion of extracellular cytokines compared to control cells in the DC microenvironment. Physicochemical characterization of NPs was performed based on the polymer end groups, their viscosities, and ligand-NP bonding type. In conclusion, the DC stimulatory response was integrated to develop a relationship between the NP structure and desired immune response. Therefore, the present study narrates a comparative evaluation of some selected parameters to choose a suitable formulation useful for in vivo cancer immunotherapy.

Targeted Therapeutic Nanoparticles: An Immense Promise to Fight against Cancer.

In nanomedicine, targeted therapeutic nanoparticle (NP) is a virtual outcome of nanotechnology taking the advantage of cancer propagation pattern. Tying up all elements such as therapeutic or imaging agent, targeting ligand, and cross-linking agent with the NPs is the key concept to deliver the payload selectively where it intends to reach. The microenvironment of tumor tissues in lymphatic vessels can also help targeted NPs to achieve their anticipated accumulation depending on the formulation objectives. This review accumulates the application of poly(lactic-co-glycolic acid) (PLGA) and polyethylene glycol (PEG) based NP systems, with a specific perspective in cancer. Nowadays, PLGA, PEG, or their combinations are the mostly used polymers to serve the purpose of targeted therapeutic NPs. Their unique physicochemical properties along with their biological activities are also discussed. Depending on the biological effects from parameters associated with existing NPs, several advantages and limitations have been explored in teaming up all the essential facts to give birth to targeted therapeutic NPs. Therefore, the current article will provide a comprehensive review of various approaches to fabricate a targeted system to achieve appropriate physicochemical properties. Based on such findings, researchers can realize the benefits and challenges for the next generation of delivery systems.