Iron oxide nanoparticles (IONPs) are a new class of nanomaterials which have attracted extensive interest for application in in vivo magnetic resonance imaging (MRI) due to their intrinsic superparamagnetic and biodegradable properties. Performance of the IONPs is largely dependent upon the properties of their surface coatings, which serve to prevent nanoparticle agglomeration, reduce the risk of immunogenicity, and limit nonspecific cellular uptake. Among the coating materials studied to date, chitosan has drawn considerable attention. Commonly derived from crustacean shells, chitosan is a natural linear polysaccharide and has ample reactive functional groups that can serve as anchors for conjugation of therapeutics, targeting ligands, and imaging agents. Because of these unique attributes, chitosan-coated IONPs are becoming more desirable for cancer imaging and therapy applications. This chapter discusses the current advances and challenges in synthesis of chitosan-coated IONPs, and their subsequent surface modifications for applications in cancer diagnosis and therapy.
The cationic nanoparticles (NPs) for targeted gene delivery is conventionally evaluated using 2D in vitro cultures. However, this does not translate well to corresponding in vivo studies because of the marked difference in NP behavior in the presence of the tumor microenvironment. In this study, we investigated if prostate cancer (PCa) cells cultured in three–dimensional (3D) chitosan-alginate (CA) porous scaffolds could model cationic nanoparticle-mediated gene targeted delivery to tumors in vitro. We assessed in vitro tumor cell proliferation, formation of tumor spheroids, and expression of marker genes that promote tumor malignancy in CA scaffolds. The efficacy of NP targeted gene delivery was evaluated in PCa cells in 2D cultures, PCa tumor spheroids grown in CA scaffolds, and PCa tumors in a mouse TRAMP-C2 flank tumor model. PCa cells cultured in CA scaffolds grew into tumor spheroids and displayed characteristics of higher malignancy as compared to those in 2D cultures. Significantly, targeted gene delivery was only observed in cells cultured in CA scaffolds whereas cells cultured on 2D plates showed no difference in gene delivery between targeted and non-target control NPs. In vivo NP evaluation confirmed targeted gene delivery indicating that only CA scaffolds correctly modeled NP-mediated targeted delivery in vivo. These findings suggest that CA scaffolds serve as a better in vitro platform than 2D cultures for evaluation of NP-mediated targeted gene delivery to PCa.
Immunotherapy has demonstrated great clinical success in certain cancers, driven primarily by immune checkpoint blockade and adoptive cell therapies. Immunotherapy can elicit strong, durable responses in some patients, but others do not respond, and to date immunotherapy has demonstrated success in only a limited number of cancers. To address this limitation, combinatorial approaches with chemo‐ and radiotherapy have been applied in the clinic. Extensive preclinical evidence suggests that hyperthermia therapy (HT) has considerable potential to augment immunotherapy with minimal toxicity. This progress report will provide a brief overview of immunotherapy and HT approaches and highlight recent progress in the application of nanoparticle (NP)‐based HT in combination with immunotherapy. NPs allow for tumor‐specific targeting of deep tissue tumors while potentially providing more even heating. NP‐based HT increases tumor immunogenicity and tumor permeability, which improves immune cell infiltration and creates an environment more responsive to immunotherapy, particularly in solid tumors.
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