In recent years, significant efforts have concentrated on nanoscale delivery systems of DOX. However, it has considerable toxicity, which limits its therapeutic use, preventing treatment at high dosages, and it has an acquired resistance excluding repeated treatment at tolerated dosages. The anticancer drug doxorubicin (DOX) is potent and therapeutically efficient for treatment of a variety of tumors. DOX-nanoconjugates were found stable under physiological conditions and shown to successfully inhibit in vitro cancer cell growth of several invasive breast carcinoma cell lines such as MDA-MB-231 and MDA-MB- 468 and of primary glioma cell lines such as U87MG and U251. For delivery into recipient cancer cells, DOX was conjugated via pH-sensitive hydrazone linkage along with polyethylene glycol (PEG) to a biodegradable, non-toxic and non-immunogenic nanoconjugate platform: poly(β- l-malic acid) (PMLA). This is why in our work we aimed to improve DOX delivery and reduce the toxicity by chemical conjugation with a new nanoplatform based on polymalic acid. However, a major drawback remains its toxicity to healthy tissue and the development of multi-drug resistance during prolonged treatment. Doxorubicin (DOX) is currently used in cancer chemotherapy to treat many tumors and shows improved delivery, reduced toxicity and higher treatment efficacy when being part of nanoscale delivery systems.
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