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1.5 Constraints and Challenges of Nanovaccines

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A successful vaccine requires a solid understanding of the physiological and immunological characteristics of any disease. Nanovaccines are widely using for treating numerous infectious and non-infectious diseases; their efficiency in stimulating our immune response to infections may be expected to be more significant. Understanding the properties of NPs and how they interact with cells can help to develop safer nanovaccines. NPs have toxicity, which must be addressed judiciously to maximize their utilization. The toxic effects and immunological responses generated by NPs are influenced by their composition, size, charge, shape, hydrophobicity, and route of exposure. NPs cause cellular injury in a size-dependent manner because smaller nanoparticles are more active, they can do more damage. NPs can easily penetrate alveoli, where they can aggregate and cause pulmonary inflammation [110, 111]. On the other hand, repetitive exposure to NPs damages the lung cells, allowing them to penetrate blood vessels and travel from lung tissue to other organs via systemic circulation. The shape of NPs plays a role in their toxicity; for example, nanofibers are shown to be more cytotoxic than spherical NPs of the same composition [112]. NPs with a low solubility or disintegration rate accumulate in cells and tissues, where they persist for a long time, such as rat nasal exposure to Au NPs lasted 15 days. Ag NPs aggregates accumulated in the lungs for 7 days [113]. NPs that penetrate the cell can increase the reactive oxygen species (ROS). The accumulating ROS interacts with the protein machinery of cell, affecting all metabolic activities in the cell. They also exhibit mitochondrial toxicity and nuclear DNA damage. Apoptosis occurs when a cell is exposed in this way [114]. As a result, high concentrations of NPs or their accumulation cause disturbance of cellular homeostasis. It can be concluded that NPs may cause tissue damage, resulting in local and systemic pathophysiological disorders. Some of the drawbacks of nanovaccines are related to their stability [115]. Increased production of nanovaccines is also an important concern due to their activity and cost-effective manufacturing process. Several loading of various components, such as antigens and adjuvants in a single nanoplatform, is complex and becoming more complicated. These drawbacks can cause side effects and/or poor immunogenicity, making them unsuitable for clinical use. Furthermore, the understanding of the details on how NPs interact with immune cells is not adequate. In fact, their adjuvant effect and ability to activate the immune system are still unknown at the molecular level and need to be better understood [116]. As a result, a deep study of nanotoxicity, immune response, and excretion of NPs over time should be conducted for safety and reliability purposes.

Nanovaccinology as Targeted Therapeutics

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