RETRACTED: Folic acid mediated endocytosis enhanced by modified multi stimuli nanocontainers for cancer targeting and treatment: Synthesis, characterization, in-vitro and in-vivo evaluation of therapeutic efficacy

Abstract

Abstract Polymeric materials are in the epicenter of scientific research the last decade and have been used in a range of pharmaceutical and biological applications. Multifunctional polymeric materials are capable targeting agents, which can be used as controlled drug release vehicles for the enhancement of therapeutic efficacy, as well as for diagnostic purposes. A newer generation of these smart polymeric entities constitutes of smart nanocontainers (NCs), which can navigate the drug to specific areas by avoiding random distribution, and thus resulting in drug toxicity reduction. The combination of pH, thermo and redox sensitivity of the multi stimuli NCs can help to achieve specific release of the drug in the tumor area, where these sensitivity parameters can be observed. Hollow polymeric multi stimuli fluorescent tNCs based on N-(2-Hydroxypropyl)methacrylamide (HPMA) were successfully functionalized with a specific targeting moiety; folic acid, and then characterized morphologically, by scanning electron and transmission electron microscopy, as well as structurally, by Fourier-transform infrared spectroscopy. Their targeting mechanism was investigated in vitro in cervical cancer cell lines and in vivo in tumor bearing mice. According to our results the folic acid functionalized NCs targeted HeLa cells’ surface within the first 30 min of treatment. Human tumor xenografted mice (nonobese diabetic/severe combined immunodeficient) were injected with folate functionalized NCs and their tumor uptake was estimated by γ-imaging at about 3.5%. The targeting efficiency of the folate functionalized NCs was investigated directly in vivo by γ-imaging and indirectly by a tumor efficacy protocol.