Advances in Cancer Nanotheranostics for Experimental and Personalized Medicine

Molecular profiling of diseases identifies specific cancer-causing genes and associated networks. Administered drug displays different therapeutic efficiency depending on individual cancer subtype and therapeutic responses. Personalized medicine helps designing treatment methods for individual patients with distinct diseases. For complete understanding of patient’s pathophysiology, different omics data types are integrated. These data can be derived from whole-exome sequencing, metabolomics, pharmacogenomics, and proteomics. Pharmacogenomics deals with the interaction of drug and patient’s genetic make-up and metabolomics reveals custom regulation of biochemical pathways in patients. Transcriptomics and proteomics analyze organism tissue or cell type in cancer and play even more relevant role in personalized medicine. Since associated genetic anomalities and metabolic profiles influence therapy response, a continuous evolution of cancer nanotheranostics helps preventing and treating the disease more precisely.

The fate of cancer cells is predicted not only by its intrinsic oncogenic engines, but also by its surrounding milieu. Beyond the tumor margin at the tumor microenvironment (TME), there is an orchestra of immune cells and soluble mediators known as the cellular and non-cellular components of TME that shape the tumor architecture. Several reports have focused on immune cells influencing the cellular components of the TME, therefore the main focus of our chapter will be the noncellular components of TME. The non-cellular components of TME include cytokines, chemokines, growth factors, inflammatory and extra-cellular matrix remodeling enzymes that are released by the tumor cells or associated immune cells in the TME. These soluble mediators outline the progression of the disease by mediating the communication taking place between the tumor cell itself and its surrounding. Considering that TME is a critical determinant in unraveling the complexity of cancer cells, thus, zooming in at the TME would definitely help us pave the road for new combinatory immuno-oncological interventions incorporating the TME in their mechanism of action and thus lowering the chances of relapse rates among cancer patients.

Our immune system protects our body from a large number of threats. External threats include pathogens from various sources. Internally, the cells of our immune system continuously fight cancer cells and thereby prevent tumor development. Immunotherapies which employ monoclonal antibodies have significantly enriched our vision of cancer treatment. Unleashing the checkpoint blockade of tumors mobilizes the cytotoxic T cells to eliminate cancer cells, and therefore, amplifies the anti-tumor response of the immune system. The lymphoid immune cells, particularly cytotoxic CD8 T cells, are the current focus of novel interventions such as chimeric antigen receptor (CAR) engineered T cells. Nanomedicines are predestined to target macrophages due to their high phagocytic activity and their large numbers in different types of tumors. Specifically, nanomedical formulations might additionally explore the potential of modulating macrophages as key effector cell which can influence the tumor microenvironment. The therapeutic cargo to be delivered to cells or tissues can benefit from the “Omics” sciences and use knowledge to specifically modulate gene expression and protein generation using small non-coding RNA. Strategies to localize drug delivery have the potential to enrich nanomedicines for their potential ability to be concentrated in certain parts of the body. Such applications can rely, for instance, on magnetic fields or infrared light sensitive systems, in order to increase target specificity. Here, we put an emphasis on the applicability of the strategies to improve target specific accumulation of theranostics and discuss potential improvements of cancer immunotherapies.

The continuous advances in molecular genetics have prompt for a wealth of tools capable to modulate genome and the corresponding gene expression. These innovative technologies have broadened the range of possibilities for gene therapy, either to decrease expression of malignant genes and mutations or edition of genomes for correction of errors. These strategies rely on the delivery of therapeutic nucleic acids to cells and tissues that must overcome several biological barriers. Indeed, a key element for the success of any gene therapy formulation is the carrier agent capable to deliver the therapeutic nucleic acid moieties to a specific target and promote efficient cellular uptake, while preventing deleterious off-target effects and degradation by endogenous nucleases. The initial vectorization strategies proved to be rather immunogenic, limited in the amount of genetic material that can be packed and raised severe toxicity concerns. Nowadays, a new generation of nanotechnology-based gene delivery systems are making an impact on the way we use therapeutic nucleic acids. These nanovectorization platforms have been developed so as to show low immunogenicity, low toxicity, ease of assembly and scale-up with higher loading capacity. Some of these nanoscale systems have also allowed for controlled release system and for the simultaneous capability of monitorization of effect – nanotheranostics. Herein, we provide a review on the variety of gene delivery vectors and platforms at the nanoscale.

Despite being previously annotated as 'junk' transcriptional products, the non-coding RNA molecules (ncRNAs) have proven their indisputable role in carcinogenesis. ncRNAs are believed to act as potent oncogenic mediators or tumor suppressors in different contexts in oncology. Functionally, ncRNAs are able to modulate various processes in the cell such as chromatin re-modeling, transcription, post-transcriptional modifications and especially signal transduction. The most abundant and well-studied ncRNA molecules are the microRNAs (miRNAs/miRs). Different oncogenic signaling cascades have recently been in relation with miRNAs in a bi-directional crosstalk. Thus, this chapter offers a wider perspective towards complex networks of interactions coordinated by miRNAs specifically in Breast Cancer (BC). Nonetheless, this chapter also sheds the light onto clinical status of the miRNAs as a potential therapeutic intervention in several contexts.

Theranostics is the definition of bringing the imaging agent and therapeutic drug together in the same delivery design. The term ‘theranostic’ was first defined by John Funkhouser in 2002 and since then it became one of the most attractive fields in treatment of severe diseases. Nanoparticles (NPs) are the most suitable carrier systems due to their plasmonic and magnetic properties, active surface areas and various physicochemical properties. Development of therapeutic NPs provide both active and passive targeting, sensitive monitoring of biological circulation, effective drug carrying and releasing, longer circulation time and efficient clearance from renal system. Here in this chapter, we discussed commonly used cancer treatment theranostic NPs that utilize imaging modalities such as magnetic resonance imaging (MRI), radionuclidebased imaging; positron emission tomography (PET) and single-photon emission computed tomography (SPECT) and X-ray-computed tomography (CT).

An optimized and particular cancer therapy must deliver the right type of treatment to the right targeted tissue to achieve control of the disease efficiently with minimal local and systemic toxicity and side effects. Advances in nanotechnology have introduced some approaches that offer new alternatives to diagnose and treat after being used in medicine. When the hydrophilic molecules are attached as carrier particles, they may remain in circulation for longer, which leads to the target organ. These new advances in recent years in nanotheranostics have expanded this concept and allowed characterization of individual tumors, prediction of nanoparticle–tumor interactions, and creation of tailor-designed new nanomedicines for individualized treatment in medicine. Advances in imaging technologies used in diseases, in general, have resulted in additional consortium guidelines for standardizing diagnostic imaging in clinical oncology. Diagnostic imaging using Ultrasonography (US), Computed Tomography (CT), Magnetic Resonance Imaging (MRI), and Positron Emission Tomography (PET) have been the most important tools. Nuclear Imaging allows a proper diagnosis, much earlier treatment, and better follow up opening a new door by non-invasive in vitro/ex vivo assessments in the oncology field and for personalized medicine. A nanotheranostic probe for nuclear medicine gives combined diagnostic and therapeutic capabilities by radiolabeling the different emitters (α, β+, β-, γ) used for imaging and/or therapy. The radiolabeled nanoparticles consist of the labeling of radionuclides onto the nanomaterials that cause deeper penetration increasing internal radiotherapy in cancer cells and inducing cell death. An ideal radionuclide nanotheranostic probe has properties such as long shelf life, easily accessible radionuclides, convenient half-life, easy and high marking efficiency, in vivo stability, lack of immunological reaction, rapidly clearance from circulation and directed to the target, high image quality, retention of radionuclide in the liposome and its metabolites should be non-toxic. The emergence and its further development of the nanotheranostic concept illustrate the need for a multidisciplinary approach with the common objective of improving the management of clinical oncology trials. The simultaneous yield of imaging in radiologic and nuclear medicine applications and therapeutic agents offer the possibility of diagnosis and treatment feedbacks on the treatment effectiveness in real-time.