Theranostics has emerged in recent years to provide an efficient and safer alternative in cancer management. This review presents an updated description of nanotheranostic formulations under development for skin cancer (including melanoma), head and neck, thyroid, breast, gynecologic, prostate, and colon cancers, brain-related cancer, and hepatocellular carcinoma. With this focus, we appraised the clinical advantages and drawbacks of metallic, polymeric, and lipid-based nanosystems, such as low invasiveness, low toxicity to the surrounding healthy tissues, high precision, deeper tissue penetration, and dosage adjustment in a real-time setting. Particularly recognizing the increased complexity and multimodality in this area, multifunctional hybrid nanoparticles, comprising different nanomaterials and functionalized with targeting moieties and/or anticancer drugs, present the best characteristics for theranostics. Several examples, focusing on their design, composition, imaging and treatment modalities, and in vitro and in vivo characterization, are detailed herein. Briefly, all studies followed a common trend in the design of these theranostics modalities, such as the use of materials and/or drugs that share both inherent imaging (e.g., contrast agents) and therapeutic properties (e.g., heating or production reactive oxygen species). This rationale allows one to apparently overcome the heterogeneity, complexity, and harsh conditions of tumor microenvironments, leading to the development of successful targeted therapies.

Polyoxometalates (POMs) are of increasing interest due to their proven anticancer activities. Aquaporins (AQPs) were found to be overexpressed in tumors bringing particular attention to their inhibitors as anticancer drugs. Herein, we report for the first time the ability of polyoxotungstates (POTs), such as of Wells–Dawson P₂W₁₈, P₂W₁₂, and P₂W₁₅, and Preyssler P₅W₃₀ structures, to affect aquaporin-3 (AQP3) activity and impair melanoma cell migration. The tested POTs were revealed to inhibit AQP3 function with different effects, with P₂W₁₈, P₂W₁₂, and P₅W₃₀ being the most potent (50% inhibitory concentration (IC₅₀) = 0.8, 2.8, and 3.2 µM), and P₂W₁₅ being the weakest (IC50 > 100 µM). The selectivity of P₂W₁₈ toward AQP3 was confirmed in yeast cells transformed with human aquaglyceroporins. The effect of P₂W₁₂ and P₂W₁₈ on melanoma cells that highly express AQP3 revealed an impairment of cell migration between 55% and 65% after 24 h, indicating that the anticancer properties of these compounds may in part be due to the blockage of AQP3-mediated permeability. Altogether, our data revealed that P₂W₁₈ strongly affects AQP3 activity and cancer cell growth, unveiling its potential as an anticancer drug against tumors where AQP3 is highly expressed.

Aim: Preclinical evaluation of a cytotoxic copper(II) complex formulated in long circulating nanoliposomes for melanoma treatment. Materials & methods: Liposomal nanoformulations of the copper complex were characterized in terms of thermodynamic behavior (differential scanning calorimeter), pH-sensitivity (spectrophotometry) and antiproliferative effects against murine melanoma B16F10 cells in vitro. Preclinical studies were performed in a C57BL/6 syngeneic melanoma model. Results: Nanoformulations were thermodynamically stable, and CHEMS-containing nanoliposomes were pH-sensitive and preserved the antiproliferative properties of the copper compound. These nanoformulations significantly impaired tumor progression in vivo, devoid of toxic side effects, compared with control mice or mice treated with the free metallodrug. Conclusion: Copper complex-containing nanoliposomes demonstrate high anticancer efficacy and safety, constituting a step forward to the development of more effective therapeutic strategies...