Nanomedicine, a promising area of medicine, employs nanosized tools for the diagnosis, prevention, and treatment of disease. Particularly, liposomes, lipid-based nanovesicles, are currently one of the most successful nanosystems, with extensive applications in the clinic and an increasing pipeline of products in preclinical and clinical development. These versatile nanotechnological tools are biocompatible and biodegradable, and can load a variety of molecules and, ultimately, improve the therapeutic performance of drugs while minimizing undesired side effects. In this review, we provide a brief description on liposomes’ composition and classification and mainly focus on their clinical use in various areas, including disease management (e.g., cancer, fungal and bacterial infections, ocular pathologies), analgesia, vaccination, diagnostics, and immunosuppression in organ transplantation. Herein are described examples of current liposomal products already in the clinic, as well as the most recent clinical trials involving liposomes as effective and safe nanomedicine tools.

Designing new metallodrugs for anticancer therapy is a driving force in the scientific community. Aiming to contribute to this field, we hereby report the development of a Schiff base (H₂L) derived from the condensation of 2-carbaldehyde-8-hydroxyquinoline with 2-hydrazinobenzothiazole and its complexation with transition metal ions. All compounds were characterised by analytical and spectroscopic techniques, which disclosed their structure: [Cu(HL)Cl], [Cu(HL)₂], [Ni(HL)(acetate)], [Ni(HL)₂], [Ru(HL)Cl(DMSO)], [VO(HL)₂] and [Fe(HL)₂Cl(H₂O)]. Different binding modes were proposed, showing the ligand’s coordination versatility. The ligand proton dissociation constants were determined, and the tested compounds showed high lipophilicity and light sensitivity. The stability of all complexes in aqueous media and their ability to bind to albumin were screened. Based on an antiproliferative in vitro screening, [Ni(HL)(acetate)] and [Ru(HL)Cl(DMSO)] were selected for further studies aiming to investigate their mechanisms of action and therapeutic potential towards colon cancer. The complexes displayed IC₅₀ < 21 μM towards murine (CT-26) and human (HCT-116) colon cancer cell lines. Importantly, both complexes exhibited superior antiproliferative properties compared to the clinically approved 5-fluorouracil. [Ni(HL)(acetate)] induced cell cycle arrest in S phase in CT-26 cells. For [Ru(HL)Cl(DMSO)] this effect was observed in both colon cancer cell lines. Additionally, both compounds significantly inhibited cell migration particularly in the human colon cancer cell line, HCT-116. Overall, the therapeutic potential of both metal complexes was demonstrated.

Melanoma stands as the most aggressive form of skin cancer. The lack of effective and safe therapies has led to the investigation of innovative strategies. The present work validates the in vitro and in vivo antimelanoma activity of new copper complexes of 8-hydroxyquinoline (8HQ) derivatives in free or liposomal forms. Firstly, the cytotoxic properties of several copper-based complexes were screened towards human (A375) and murine (B16F10) melanoma cell lines and human dermal fibroblasts or keratinocytes (HaCaT) cell lines. All the complexes presented lower IC₅₀ values (80 μM). Aiming to solve low specificity against tumor cells and enhance its targetability to affected sites three metal-based complexes were selected, based on their antiproliferative properties, and incorporated in long blood circulating liposomes. One of them, di-2-(((2-morpholinoethyl)imino)methyl)quinolin-8-olCopper(II), designated as LCR35, was selected for further studies due to the highest incorporation parameters and cytotoxic properties observed. The antiproliferative activity of LCR35 was preserved after its association to liposomes. Moreover, in B16F10 cells this effect was potentiated. Furthermore, cell cycle analysis studies in A375 and B16F10 cell lines were performed to elucidate the mechanism of action of copper-based complex formulations. A cell cycle arrest at G2/M and G0/G1 phases in A375 and B16F10 cells, respectively, both in free and liposomal forms were observed. To validate the therapeutic potential of LCR35 two murine melanoma models were carried out: subcutaneous and metastatic. Pre-clinical studies demonstrated the high therapeutic effect of LCR35, especially after incorporation in liposomes, compared to control group or animals that received LCR35 Free and DTIC. Overall, in vitro and in vivo studies highlight the potential antimelanoma properties of the copper-based complex, LCR35.