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Exosomes are nanovesicles formed in the endosomal pathway with an important role in paracrine and autocrine cell communication. Exosomes secreted by cancer cells, malicious exosomes, have important roles in tumor microenvironment maturation and cancer progression. The knowledge of the role of exosomes in tumorigenesis prompted a new era in cancer diagnostics and therapy, taking advantage of the use of circulating exosomes as tumor biomarkers due to their stability in body fluids and targeting malignant exosomes’ release and/or uptake to inhibit or delay tumor development. In recent years, nanotechnology has paved the way for the development of a plethora of new diagnostic and therapeutic platforms, fostering theranostics. The unique physical and chemical properties of gold nanoparticles (AuNPs) make them suitable vehicles to pursuit this goal. AuNPs’ properties such as ease of synthesis with the desired shape and size, high surface:volume ratio, and the possibility of engineering their surface as desired, potentiate AuNPs’ role in nanotheranostics, allowing the use of the same formulation for exosome detection and restraining the effect of malicious exosomes in cancer progression.

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Resistance to chemotherapy is a major problem facing current cancer therapy, which is continuously aiming at the development of new compounds that are capable of tackling tumors that developed resistance toward common chemotherapeutic agents, such as doxorubicin (DOX). Alongside the development of new generations of compounds, nanotechnology-based delivery strategies can significantly improve the in vivo drug stability and target specificity for overcoming drug resistance. In this study, multifunctional gold nanoparticles (AuNP) have been used as a nanoplatform for the targeted delivery of an original anticancer agent, a Zn(II) coordination compound [Zn(DION)2]Cl2 (ZnD), toward better efficacy against DOX-resistant colorectal carcinoma cells (HCT116 DR). Selective delivery of the ZnD nanosystem to cancer cells was achieved by active targeting via cetuximab, NanoZnD, which significantly inhibited cell proliferation and triggered the death of resistant tumor cells, thus improving efficacy. In vivo studies in a colorectal DOX-resistant model corroborated the capability of NanoZnD for the selective targeting of cancer cells, leading to a reduction of tumor growth without systemic toxicity. This approach highlights the potential of gold nanoformulations for the targeting of drug-resistant cancer cells.

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The design and preparation of highly efficient drug delivery platforms using green methodologies is at the forefront of nanotherapeutics research. POxylated polyurea dendrimers are efficiently synthesized using a supercritical-assisted polymerization in carbon dioxide. These fluorescent, pH-responsive and water-soluble core-shell smart nanocarriers show low toxicity in terms of cell viability and absence of glutathione depletion, two of the major side effect limitations of current vectors. The materials are also found to act as good transfection agents, through a mechanism involving an endosomal pathway, being able to reduce 100-fold the IC50 of paclitaxel.

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Over the past few years, modern medicinal chemistry has evolved towards providing us new and alternative chemotherapeutic compounds with high cytotoxicity towards tumor cells, alongside with reduced side effects in cancer patients. Organometallic compounds and their unique physic-chemical properties typically used in homogenous catalysis are now being translated as potential candidates for medical purposes. Their structural diversity, ligand exchange, redox and catalytic properties make them promising drug candidates for cancer therapy. Over the last decade this area has witnessed a steady growth and a few organometallic compounds have in fact already entered clinical trials, emphasizing its increasing importance and clinical relevance. Here we intend to stress out the different applications of organometallic compounds in medicine with emphasis on cancer therapy, as well as address setbacks regarding formulation issues, systemic toxicity and off-target effects. Advantages over classical coordination metal complexes, their nanovectorisation and specific molecular targets are also discussed.

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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.