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Aims: Advanced melanoma is characterized by poor outcome. Despite the number of treatments having been increased over the last decade, current pharmacological strategies are only partially effective. Therefore, the improvement of the current systemic therapy is worthy of investigation. Methods: a nanotechnology-based poly-chemotherapy was tested at preclinical level. Temozolomide, rapamycin, and bevacizumab were co-loaded as injectable nanoemulsions for total parenteral nutrition (Intralipid®), due to suitable devices, and preliminarily tested in vitro on human and mouse cell models and in vivo on the B16-F10 melanoma mouse model. Results: Drug combination was efficiently loaded in the liquid lipid matrix of Intralipid®, including bevacizumab monoclonal antibody, leading to a fast internalization in tumour cells. An increased cytotoxicity towards melanoma cells, as well as an improved inhibition of tumour relapse, migration, and angiogenesis were demonstrated in cell models for the Intralipid®-loaded drug combinations. In preliminary in vivo studies, the proposed approach was able to reduce tumour growth significantly, compared to controls. A relevant efficacy towards tumour angiogenesis and mitotic index was determined and immune response was involved. Conclusions: In these preliminary studies, Intralipid® proved to be a safe and versatile poly-chemotherapy delivery system for advanced melanoma treatment, by acting on multiple mechanisms. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX) is an anthracycline widely used in cancer therapy and in particular in breast cancer treatment. The treatment with DOX appears successful, but it is limited by a severe cardiotoxicity. This work evaluated the in vitro and in vivo anticancer effect of a new formulation of β-cyclodextrin nanosponges containing DOX (BNS-DOX). The BNS-DOX effectiveness was evaluated in human and mouse breast cancer cell lines in vitro in terms of effect on cell growth, cell cycle distribution, and apoptosis induction; and in vivo in BALB-neuT mice developing spontaneous breast cancer in terms of biodistribution, cancer growth inhibition, and heart toxicity. BNS-DOX significantly inhibited cancer cell proliferation, through the induction of apoptosis, with higher efficiency than free DOX. The breast cancer growth in BALB-neuT mice was inhibited by 60% by a BNS-DOX dose five times lower than the DOX therapeutic dose, with substantial reduction of tumor neoangiogenesis and lymphangiogenesis. Biodistribution after BNS-DOX treatment revealed a high accumulation of DOX in the tumor site and a low accumulation in the hearts of mice. Results indicated that use of BNS may be an efficient strategy to deliver DOX in the treatment of breast cancer, since it improves the anti-cancer effectiveness and reduces cardiotoxicity. [ABSTRACT FROM AUTHOR]