Synthesis of antitumor modular conjugates for the preparation of nanocarriers with high affinity for endogenous albumin

Research on novel and more effective anticancer treatments has increasingly developed in the last decades. Among carcinomas, breast cancer has the highest incidence among women and its impact is steadily growing. According to the WHO, in 2020 there were 2.3 million women diagnosed with breast cancer and 685,000 deaths globally. As of the end of 2020, there were 7.8 million women alive who were diagnosed with breast cancer in the past 5 years, making it the world’s most prevalent cancer. Among breast cancer subtypes, triple negative breast cancer (TNBC) still lacks targeted and effective treatments options. Accounting for approximately 15–20% of all breast carcinomas, TNBC is associated with younger age of onset, aggressive clinical course, and dismal prognosis compared to hormone receptor and HER2-positive breast carcinomas. Despite the significant benefit provided by conventional chemotherapy and monoclonal antibodies in the prognosis of breast cancer patients, the treatment of this disease remains a great challenge. Based on this, the aim of this work has been the development of a “prodrug-based and bioresponsive approach” to selectively target breast cancer cells. Through the setup of several synthetic procedures, we successfully designed and synthesized innovative paclitaxel (PTX) and epi-paclitaxel (epi-PTX) modular prodrugs capable of forming redox-sensitive nanoparticles able to specifically bind endogenous human serum albumin (HSA), to be selectively carried and released at the tumour site.