Nanomedicine is a field at the interface of medicine and pharmacy encompassing very small technologies, ranging from 1 to 1000 nm, to treat or diagnose diseases. The use of nanoscale materials allows for an appropriate concentration of a drug at the target site of action. It can be understood as a part of personalized medicine in this sense [119]. Nanomaterials used in medicine and pharmacy can be divided into three main types: polymers, inorganic nanoparticles, and lipid technologies, especially liposomes. These technologies have found their practical application and, currently, there are medicinal products on the market using all the forms mentioned above. One of the first FDA-approved drugs used in oncology were liposomal forms of doxorubicin (Doxil, Janssen) and an Escherichia coli-derived conjugate of L-asparaginase with monomethoxypolyethylene glycol for the treatment of acute lymphoblastic leukemia (Oncaspar, Servier) (Mitchell MJ, 2021). The first nanosystem approved for use in photodynamic therapy was verteporfin in liposomal form (Visudyne, Novartis; Bausch and Lomb), which is currently used in AMD and CNV photodynamic therapy as well as for uveal melanoma [120,121]. Nanotechnologies play a crucial role in advancing personalized medicine in oncology. They enhance the delivery of drugs directly to tumor sites by efficiently overcoming biological barriers. Additionally, nanotechnologies are valuable for enhancing the physical and chemical characteristics of drugs, contributing to their increased efficacy in treating cancer. A good example that confirms the advantages of nanomedicine to improve personalized medicine is imatinib, the first drug in the targeted therapy of chronic myeloid leukemia with the expression of the BCR-ABL fusion protein. The increase in drug delivery using nanomaterials has been shown to improve survival by 40% in a mouse leukemia model [122]. Nanomedicine may be particularly important in ophthalmology due to the specific structure of the eye and biological barriers that represent an obstacle to drug delivery [123]. Therefore, it seems that nanomedicine can be very helpful in UM therapy, where overcoming biological barriers of the eye and effective drug delivery to the tumor site are of particular importance. Current nanomedicine research on uveal melanoma uses nanoparticles to deliver cytostatic drugs and genes and increases the effectiveness of brachytherapy or photodynamic therapy. In addition to therapeutic nanoparticles, contrast agents have also been developed, which, given in the form of nanoparticles, increase the quality of the radiological images [124]. One of the most dynamically developing areas of nanomedicine is the delivery systems of miRNA—an important regulator of gene expression and one of the important molecular targets in the development of anticancer therapies. Disturbances of miRNA expression in UM are classified as epigenetic mechanisms responsible for tumorigenesis and metastasis [125]. Preclinical studies have shown that therapeutic miRNAs can inhibit the proliferation of UM tumor cells, reduce their growth, prevent metastasis, and increase susceptibility to radiation therapy. Unfortunately, the stability of miRNAs in vivo is low due to the destructive effect of serum nuclease, among other reasons. This makes it difficult to achieve the right concentration in cancer cells. To overcome this problem and protect against the degradation of miRNA molecules, drug delivery systems based on organic (polymers, liposomes, micelles, etc.) and inorganic nanoparticles of gold, silver, iron oxide, silicon, etc. [126] can be used. The synergistic cytotoxic effect of a type I topoisomerase inhibitor and miRNA was shown in the study by Milain Rois et al. [127]. It turned out that both compounds, conjugated with gold nanoparticles as carriers, showed a stronger carrier cytotoxic effect against human uveal melanoma cells. The authors emphasized that the use of gold nanoparticles as a carrier of miRNA allows to increase internalization into cells and, in the case of a cytostatic drug, solves the problem of its poor solubility in water. This technology increased the anticancer efficacy of both substances [127].

In addition to gold nanoparticles, one of the most commonly used compounds as a drug carrier in nanomedicine is albumin. This approach has also been used in the experimental therapy of uveal melanoma. Albumin-based nanostructures containing AZD8055 (ABN-AZD), a potent inhibitor of mTOR kinase, proved to be selective and showed toxicity only to uveal melanoma cells, while not affecting keratinocyte cells. Moreover, these nanostructures showed excellent in vivo activity, reducing tumor size compared to free AZD8055 in mouse models [128].

In addition to developing completely new therapeutic methods, nanomedicine is also an excellent tool for preparing new formulations and new routes of administration of known anticancer drugs. One such approach concerns an encapsulated lipid nanostructure of sorafenib for the treatment of UM. The developed technology could overcome the biological barriers to the eye and is an important step in the development of topical application of anticancer agents used in UM [129]. Another solution that used increased penetration into eye tissues and extended release was a curcumin-loaded nanoparticle/hydrogel formulation. In addition to favorable pharmacokinetic parameters, the new curcumin formulation showed significant antitumor activity against MP-38 human uveal melanoma cells [130]. Chlorin e6, a photosensitizer used in photodynamic therapy for cancer, is another example of a well-known substance used in the development of a nanoparticle. The authors of one the study proposed an innovative approach to the diagnosis and treatment of UM by using multifunctional chlorin e6 (Ce6) in poly-lactic-co-glycolic acid (PLGA) NPs and wrapping Fe III-tannic acid (Fe III-TA) nanoparticles (FTCPNPs), combining photothermal therapy (PTT) and photodynamic therapy (PDT). FTCPNPs is actually a theranostic, as it not only induces apoptosis of tumor cells through mitochondrial damage, but also works as a MRI contrast agent [131].

It should also be emphasized that apart from their undoubted advantages, nanomaterials can also be dangerous, and the assessment of their safety profile is a challenge for science and regulatory agencies. In the study of Ding et al. [132], it was shown that carbon dot (C-dot) nanoparticles at a certain concentration could increase the growth of uveal melanoma cells in a zebrafish model and nude mouse xenograft. The postulated mechanism of this phenomenon is that C-dot induces a moderate increase in ROS, resulting in the activation of the Akt/mTOR pathway and increasing glutamate metabolism, which can ultimately cause the excessive growth and aggressiveness of UM cells, as well as metastasis [132].

In 2020, at the annual ARVO conference, an interim analysis of a phase 1b/2 clinical trial of AU-a011—novel light-activated nanomedicine to treat UM was published [133]. AU-011, developed by Aura Biosciences, Inc., is a targeted therapy based on a viral carrier and a phototoxic drug. This conjugate irradiated by 689 nm wavelength light causes an increased concentration of singlet oxygen and necrosis of the cancer cell. Furthermore, damaged cells induce an antitumor immune response by releasing damage-associated molecular patterns [134]. The results of this interim analysis are very promising, as tumor growth control was observed in more than 60% of the patients, visual acuity remained unchanged in more than 90% and the safety profile was favorable.