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Immunotherapy has gathered momentum in the advanced generation of cancer therapeutics. Many unresectable resistant tumor subtypes are ideal candidates for immunotherapy; however, the efficacy is limited because of heterogeneity of both malignant cells and non-malignant cells of the tumor microenvironment, including stromal and immune cells. The success of immunotherapy is largely dependent on the population of individual immune cell types between patients of the same tumor subtype, and the expression of biomarkers that are expressed by the components of the immune system. Hence, it is imperative to first identify the components of the immune system, visualize these populations in the tumor microenvironment, and then devise specifically targeted immunotherapies. In this review, we have outlined strategies to characterize the cellular components of the immune system with clinically relevant imaging modalities. The importance of high dimensional analyses including mass cytometry and unbiased single-cell RNA sequence analysis in visualizing the ideal candidates for immunotherapy has been discussed. This review stresses the importance of immuno-imaging as a means to further develop targeted immunotherapies for cancer.

The goal of this chapter is to concisely introduce the most important noninvasive animal/preclinical imaging approaches that are used to image cancer models today. It is the scope of this chapter to discuss a subsection on models that are truly representative of the tumor microenvironment and highlight its applications, advantages, and translational challenges. Also, each modality’s salient advantages, considerations, and best applications will be discussed and demonstrated with examples from the literature. The altering nature of modeling cancer in mice will also be mentioned briefly, primarily through utilization of ectopic, orthotopic, patient-derived xenografts models with preclinical imaging which is well positioned to increase the use of these new, accurate, and resourceful modeling approaches.

The functionalization of polylactide-co-glycolide (PLGA) nanogel is highly dependent on the solubilization of drug and drug depot entrapped in the core–shell of nanoformulations. The bare nanoformulations possess some drawbacks such as rapid clearance before reaching the targeted site via parenteral administration, poor selectivity, delayed release, low-cell targeting, and others. In the current nanotechnology arena, recent research teams have modified PLGA nanogel particles into more effective and functional carriers, bypassing or eliminating these disadvantages and produced a more effective dosage form and yielding high therapeutic potential at the targeted site. PEGylation, introduction of ligand-anchored PLGA nanoparticles, thernostics, polyplexes, micelles complexes, conjugation, and others are some of the efforts which modified the PLGA nanogel system into a more effective drug transportation nanocarrier. In this chapter we demonstrate that the current nanogel nanocarrier system exhibited advanced therapeutic functionalities compared to the conventional dosage forms or therapies. These functional and modified PLGA nanogel systems are expected to convey bioactives, chemotherapeutics, diagnostic agents, and imaging candidates in a potentially highly selective and effective mode.

Hepatocellular cellular carcinoma (HCC) is one of the most challenging liver cancer subtypes. Due to lack of cell surface biomarkers and highly metastatic nature, early detection and targeted therapy of HCC is an unmet need. Galactosamine (Gal) is among the few selective ligands used for targeting HCCs due to its high binding affinity to asialoglycoprotein receptors (ASGPRs) overexpressed in HCC. In the present work, we engineered nanoscale G4 polyamidoamine (PAMAM) dendrimers anchored to galactosamine and loaded with the potent anticancer curcumin derivative (CDF) as a platform for targeted drug delivery to HCC. In vivo targeting ability and bio-distribution of PAMAM-Gal were assessed via its labeling with the clinically used, highly contrast, near infrared (NIR) dye: S0456, with testing of the obtained conjugate in aggressive HCC xenograft model. Our results highlighted the targeted dendrimer PAMAM-Gal ability to achieve selective high cellular uptake via ASGPR mediated endocytosis and significantly enhance the delivery of CDF into the studied HCC cell lines. Cytotoxicity MTT assays in HCC cell lines, interestingly highlighted, the comparative high potency of CDF, where CDF was more potent as a chemotherapeutic anticancer small molecule than the currently in use Doxorubicin, Sorafenib and Cisplatin chemotherapeutic agents. In conclusion the proof-of-concept study using nanoscale PAMAM-Gal dendrimer has demonstrated its competency as an efficient delivery system for selective delivery of potent CDF for HCC anticancer therapy as well as HCC diagnosis via NIR imaging.

Nanogels are swollen nanosized networks composed of hydrophilic or amphiphilic polymer chains developed as carriers for drug transport. They are designed to spontaneously incorporate biologically active molecules through the formation of salt bonds, hydrogen bonds, or hydrophobic interactions. Nanogels are the nanoversion of their parent hydro gels, encompassing high water uptake capability, swelling ability, degradability, and pH-sensitivity. These qualities make them appropriate as responsive nanocarriers in innovative drug delivery systems. They play a vital role by addressing the problems associated with chronic and modern therapeutics, such as nonspecific effects and poor stability. The nanostructured hydrogel molecules combined with bacterial enzymes are shown to trigger antibiotic release by degrading the polymeric core. The targeted nanogel preferentially delivers drugs to either macrophages or onto the invading microbes, leading to drug accumulation at bacterial infection sites, consequently providing lesion site-responsive drug release properties, which inhibit bacterial growth. The antigen-specific immune responses induced by novel Nanogel vaccine have shown to effectively protect animals against pathogens such as Streptococcus pneumoniae , making it ideal for tunable degradability, screening excellent blood compatibility, cytocompatibility, and cellular localization when tested on various cell lines. Thus the pursuit of this chapter is to concisely describe the recent development of nanogel drug delivery system in terms of its efficacy in antimicrobial chemotherapy.

This chapter outlines the challenges associated with effective drug and gene delivery to tumors, and strategic approaches to augment the efficacy of anticancer agents by utilizing multifunctional nanosystems. Extensive knowledge of the chemistry of biomaterials, surface engineering, and the ability to manipulate materials at the nanoscale, coupled with current understanding of tumor biology, enables us to utilize customizable combinatorial design principles to arrive at modular platforms for tailoring drug delivery systems based on the characteristics of target tumors. Illustrative examples from the existing scientific literature demonstrate the versatility of such multifunctional nanosystems, and accentuate the effectiveness of this multi-pronged approach in the diagnosis and therapy of cancer. The chapter finally summarizes the importance of material safety considerations for regulatory approval, especially the guidelines governing the progress of a pharmaceutical candidate from quality-by-test to quality-by-design.