Table 8.

The challenges regarding the application of nanoparticles in cancer immunotherapy

Nanoparticles	Benefits	Challenges
Polymeric nanoparticles	• Targeted delivery of cargo to improve the therapeutic index and reduce the systemic side effects • Prolonged release of drugs • Potential in the delivery of various cargoes including small molecule drugs, proteins, peptides, and nucleic acids • Increased stability of drugs and preventing degradation • Stimulation of the immune system • Biocompatibility and biodegradability	• The development of nanoparticles with desirable size, charge, and targeting capacity is challenging • Strict rules regarding clinical application • Unexpected interactions with the immune system • Challenges in the scale-up generation, storage and stability
Lipid nanoparticles	• Efficient delivery of genetic tools including mRNA, siRNA, and DNA • Targeted delivery • Protection of cargo • Long-term biocompatibility and safety • Adjuvant impact that a number of lipid components can function as adjuvants and increase anti-cancer immune responses	• Complex manufacturer production, especially the development of nanoparticles for gene delivery • They require ultra-low temperatures to preserve their stability • Immunogenicity that can lead to inflammation and other side effects • Low loading capacity
Metal nanoparticles	• Targeted delivery of drugs and high loading and encapsulation efficiencies • Application for photothermal therapy, since a number of nanostructures such as gold nanocarriers can absorb light and cause photothermal-mediated tumor ablation • Delivery of immunomodulatory agents for cancer immunotherapy • Synergistic therapy through a combination of drug delivery and photothermal therapy • Imaging and biosensing	• The biodistribution of metal nanostructures is challenging along with their clearance from the body • The metal nanostructures possess high cytotoxicity and poor biocompatibility • The chance of inflammation and immune reactions • Stability and toxicity towards normal cells
Carbon nanoparticles	• High drug-loading potential for the delivery of drugs, proteins, and genetic tools • Application in photothermal and photodynamic therapy • Imaging and biosensing of cancer biomarkers	• The toxicity and poor biocompatibility • The changes in the biodegradation of carbon nanoparticles, leading to their long-term accumulation • Complexity in the generation of nanoparticles at a large scale and achieving the desirable physicochemical properties including size, zeta potential and others • Heterogeneous biological functions among the various classes of carbon nanomaterials including tubes, dots and sheets