Dianzani Chiara, Monge Chiara, Miglio Gianluca, Serpe Loredana, Martina Katia, Cangemi Luigi, Ferraris Chiara, Mioletti Silvia, Osella Sara, Gigliotti Casimiro Luca, Boggio Elena, Clemente Nausicaa, Dianzani Umberto, Battaglia Luigi
Department of Drug Science and Technology, University of Turin, via Pietro Giuria 9, 10125 Turin, Italy.
Department of Veterinary Sciences, University of Turin, Largo Paolo Braccini 2, 10095 Grugliasco, Italy.
Cancers (Basel). 2020 May 9;12(5):1198. doi: 10.3390/cancers12051198.
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. 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. 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. 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.
晚期黑色素瘤的特点是预后不良。尽管在过去十年中治疗方法的数量有所增加，但目前的药理学策略仅部分有效。因此，改进当前的全身治疗值得研究。一种基于纳米技术的多药化疗在临床前水平进行了测试。由于合适的制剂，替莫唑胺、雷帕霉素和贝伐单抗被共负载为用于全胃肠外营养（英脱利匹特）的可注射纳米乳剂，并在人和小鼠细胞模型上进行了体外初步测试，以及在B16-F10黑色素瘤小鼠模型上进行了体内初步测试。药物组合有效地负载在英脱利匹特的液体脂质基质中，包括贝伐单抗单克隆抗体，导致其在肿瘤细胞中快速内化。在负载英脱利匹特的药物组合的细胞模型中，证明对黑色素瘤细胞的细胞毒性增加，以及对肿瘤复发、迁移和血管生成的抑制作用增强。在初步的体内研究中，与对照组相比，所提出的方法能够显著降低肿瘤生长。确定了对肿瘤血管生成和有丝分裂指数的相关疗效，并且涉及免疫反应。在这些初步研究中，英脱利匹特被证明是一种通过多种机制作用于晚期黑色素瘤治疗的安全且通用的多药化疗递送系统。
