Manufacturing and biological evaluations of stimuli-responsive polymersomes towards enhanced efficacy of cancer therapies

Abstract

The most recent survey by the International Agency for Research on Cancer reported that the global death related to the malignancy was about 9.6 million in 2018 (21% higher than that in 2008). This number is predicted to be as high as 19.3 million by 2025 calling for improvements in cancer treatments. In the last decades, cancer therapy has also been tackled to design carriers that can navigate the body and deliver their cargos in desired site. The most successful up-to-date carrier is the pegylated liposomal formulation of doxorubicin (DOX) Doxil/Caelyx which is 100nm-sized vesicles encapsulating 10,000-15,000 DOX molecules. Doxil/Caelyx becomes one of the most sale nanotechnologies in the history of the chemotherapy which expected to generate revenue of 1.39 billion USD for 2025.Despite a 60-fold increase in the fraction of recovered dose in blood, a 4-fold increase of the recovered dose in liver and spleen and a 25-fold increase of the concentration of the liposomal formulation in tumor, the Doxil/Caelyx formulation still compromise the effectivity of the treatment due to lack of specificity and DOX leakage during blood circulation resulting in several side-effects including hand-foot syndrome, mouth pain (stomatitis), low white blood cell counts, low platelet counts, anemia, nausea and vomiting. We wish to fundamentally contribute to circumvent such drawback by designing stimuli-responsive vesicles able to controlled release the drug only under response to the inherent characteristics of the tumor microenvironment. Such features may enhance the therapeutic outcomes in comparison to the conventional cancer therapies. (AU)