Lipid-Based Nanosystems for Gene and Drug Co-Delivery in Cancer Therapy

The medical advances made during the last century were accompanied by an increase in lifespan, leading to a shift in focus toward the healthcare needs of an ageing population. According to the World Health Organization (WHO), cancer is nowthe second leading cause of death (February 2018), responsible for nearly 1 in 6 deaths globally. The fact that approximately 70% of deaths from cancer occur in low- and middle-income countries demonstrates that this is not only a problem of industrialized countries. Strategies against cancer cover the different stages of the disease, ranging from prevention and early detection to effective treatments and palliative care. Currently, the strategies for treatment comprise surgery, radiotherapy, and chemotherapy. The latter provides the only possibility to cure metastatic cancers, since chemotherapeutic agents cause cell death and, in most cases, enter all body tissues. While a lot of chemotherapeutics are on the market (the information service CenterWatch listed 225 approved drugs in the field of oncology between 1995 and February 2018 on its website), they are often associated with pronounced side effects, because healthy cells are attacked along with malignancies. This problem particularly affects rapidly proliferating cells such as those in hair follicles, bone marrow, and the gastrointestinal tract. Encapsulating drugs within nano-sized delivery systems, especially targeted ones which are preferentially localized in tumor tissues, can help to overcome these hurdles. Furthermore, the delivery system can also help to overcome biopharmaceutical barriers more efficiently. An additional problem associated with anticancer drugs is the development of drug resistance in tumor cells. To overcome this issue, anticancer drugs are often given in combinations, increasing the risk of side effects. Current efforts to understand the genetic mechanisms of anticancer drug resistance, have given rise to the possibility that these can also be overcome using modern gene therapy strategies. This chapter will introduce lipid-based nanosystems as delivery systems for nucleic acids and small molecule anticancer drugs, which opens the possibility for an efficient, targeted, combinatorial tumor therapy.