Adaptive treatment tolerance (ATT) is one of the main obstacles in the therapeutic failure of metastasis cancer treatments in clinic. Several factors in treatment tolerance include MDR-associated proteins overexpressed in cells, inactivation of therapeutic molecules in targeted tissues, invalidation of treatments in patients, etc. This clinical obstacle was broadly explored, and different molecular mechanisms were clarified with enhanced repair mechanisms of drug induced DNA damage, lowered tumor extracellular pH, alteration of cell cycle check points, blockage of apoptosis pathway and poor tumor vasculature, respectively. There is still no significantly clinical improvement so far. Nanotechnology has been widely used in the development of new strategies for drug delivery and cancer therapy. Compared to traditional drug delivery systems, nanoscale drug delivery systems (NDDS) have greater potential in many areas, such as multiple targeting functionalization, combined drugs delivery, longer circulation time and systemic control release. NDDS incorporating stimulus-responsive biopolymer have remarkable properties which allow them to bypass biological barriers and achieve targeted intracellular drug delivery. Some of these have been translated from the bench to clinical application and approved by the Food and Drug Administration (FDA) for treatment of various cancerous diseases. With further development of biocompatible nanoformulations, it might be possible to design even more promising multiple-responsive NDDS synergistic for combined drug delivery and efficient cancer therapy in the future. Nanotechnology-based drug delivery is expected to bring new hope for cancer treatment by enhancing anticancer drug efficacy, overcoming drug resistance and reducing drug toxicity. This presentation describes the characteristic features of tumor resistance to classical chemotherapy and their mechanisms with the aid of nanoparticles for the development of newer drug delivery systems to overcome ATT in vitro and vivo.

Adaptive treatment tolerance attenuated by nanotechnique-assisted drug delivery

256th National Meeting (2018)

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