Nanotheranostics Targeting the Tumor Microenvironment

Abstract

Cancer is considered the most aggressive malignancy to humans, and definitely the major cause of death worldwide. Despite the different and heterogenous presentation of the disease, there are pivotal cell elements involved in proliferation, differentiation, and immortalization, and ultimately the capability to evade treatment strategies. This is of utmost relevance when we are just beginning to grasp the complexity of the tumor environment and the molecular “evolution” within. The tumor micro-environment (TME) is thought to provide for differentiation niches for clonal development that results in tremendous cancer heterogeneity. To date, conventional cancer therapeutic strategies against cancer are failing to tackle the intricate interplay of actors within the TME. Nanomedicine has been proposing innovative strategies to tackle this TME and the cancer cells that simultaneously provide for biodistribution and/or assessment of action. These nanotheranostics systems are usually multi-functional nanosystems capable to carry and deliver active cargo to the site of interest and provide diagnostics capability, enabling early detection, and destruction of cancer cells in a more selective way. Some of the most promising multifunctional nanosystems are based on gold nanoparticles, whose physic-chemical properties have prompt for the development of multifunctional, responsive nanomedicines suitable for combinatory therapy and theranostics. Herein, we shall focus on the recent developments relying on the properties of gold nanoparticles as the basis for nanotheranostics systems against the heterogeneity within the TME.

Post translational modification-assisted cancer immunotherapy for effective breast cancer treatment

“…CLSM analysis showed that the nanoparticles were accumulated mainly in the exterior regions compared to core regions with limited perfusion, favorable for antigen delivery to immune cells also located in tumor margins. 61,62 Finally, the biosafety of different nanoparticle formulations was analyzed. Heart, liver, kidney, lung, spleen, primary and secondary tumors were collected at the end of treatment for H & E staining (Fig.…”

Gene Therapy in Cancer Treatment: Why Go Nano?

“…As an example, pegylation of drug-loaded liposomes not only improved their blood circulation, but also increased the accumulation of the drug in the tumor [43]. Furthermore, active targeting of the nanomedicines improves greatly their efficacy (reviewed in [40,[46][47][48]). With that purpose, several biological ligands could be bind to nanomaterials, including antibodies, such as cetuximab, an FDA approved antibody against anti-epidermal growth factor receptor (EGFR) used in clinical practice for cancer treatment; glycoproteins, such as the iron-binding transferrin; polysaccharides, such as hyaluronic acid for CD44 targeting; peptides, such as arginylglycylaspartic acid (RGD) for integrins targeting; aptamers, such as AS-1411 G-rich DNA aptamer for nucleolin targeting; or other small molecules, such as folate ( [49][50][51][52][53][54][55][56][57][58][59][60], reviewed in [48]).…”

Cancer Nano-Immunotherapy from the Injection to the Target: The Role of Protein Corona

“…However, this dose increase could trigger undesired side effects harmful to the patients. This limitation makes NPs ideal candidates for the delivery of cancer immunotherapy since they follow different pharmacokinetics and pharmacodynamics compared to free drugs [60,61].…”