Circumventing tumor resistance to chemotherapy by nanotechnology

Abstract

Patient relapse and metastasis of malignant cells is very common after standard cancer treatment with surgery, radiation, and/or chemotherapy. Chemotherapy, a cornerstone in the development of present day cancer therapy, is one of the most effective and potent strategies to treat malignant tumors. However, the resistance of cancer cells to the drugs remains a significant impediment to successful chemotherapy. An additional obstacle is the inability of chemotherapeutic drugs to selectively target tumor cells. Almost all the anticancer agents have severe side effects on normal tissues and organs. The toxicity of currently available anticancer drugs and the inefficiency of chemotherapeutic treatments, especially for advanced stages of the disease, have limited the optimization of clinical drug combinations and effective chemotherapeutic protocols. Nanomedicine allows the release of drugs by biodegradation and self-regulation of nanomaterials in vitro and in vivo. Nanotechnologies are characterized by effective drug encapsulation, controllable self-assembly, specificity and biocompatibility as a result of their own material properties. Nanotechnology has the potential to overcome current chemotherapeutic barriers in cancer treatment, because of the unique nanoscale size and distinctive bioeffects of nanomaterials. Nanotechnology may help to solve the problems associated with traditional chemotherapy and multidrug resistance.

Fig. 21.1

Mechanisms of clinical multidrug resistance during anticancer therapy. A number of mechanisms might be responsible for pleiotropic drug resistance in the clinic. Cellular resistance to chemotherapy is associated with overexpression of ABC membrane transporters such as Pgp, Mrp or BRCP that are responsible for “pumping” drugs out of cancer cell. Cytoskeletal disruption and other alterations prevent the correct localization of membrane proteins, and disrupted cell signaling in cancer cells may lead to drug resistance. Abnormal vasculature reduces the efficient biodistribution of anticancer drugs, resulting in less drug accumulation in the tumor.