Research Projects

Drug delivery using a nanocarrier is the most efficient strategy for the treatment for cancer. However, it suffers from several drawbacks, which include (i) nanocarriers in most of the cases themselves have no therapeutic value, (ii) targeted delivery, (iii) biocompatibility and (iv) toxicity of the nanocarrier. Hence, there is a high demand for the design of nanocarriers that are (i) biocompatible, (ii) stimuli-responsive, (iii) permit nearly 100% delivery of the encapsulated drug at targeted site and (iv) undergoes self-degradation. Moreover, if the nanocarrier itself is having therapeutic value then fate of the nanocarrier after the delivery will then not be a concern. DNA-based nanostructures have received enormous attention in recent years due to their unique self-assembly behavior and unparalleled biocompatibility. By exploring the stimuli-responsive nature of DNA nanostructures, their potential as a nanocarrier for targeted cancer therapy have been demonstrated. Herein, we propose a new class of stimuli-responsive DNA-amphiphiles, which contains therapeutically relevant DNA (antisense) as the hydrophilic segment attached to a stimuli-responsive hydrophobic moiety through a cleavable linker. The amphiphile self-assemble into nanoparticles with hydrophobic core decorated with hydrophilic antisense DNA. Anticancer drug such as Doxorubicin can be loaded into the nanostructure during the self-assembly. The hydrophilic corona not only acts as the therapeutic agent but also permits the integration of cell targeting units via DNA hybridization. The hydrophobic part is designed in such a way that they undergo specific reaction inside the cancer cells (not in healthy cells) by exploring the peculiar behaviors of cancerous cells. We explore the low pH/high concentration of H₂O₂/over expression of different enzymes as the triggers. Accordingly, hydrophobic groups undergo one of the reactions inside the cancer cells; (i) H₂O₂ mediated oxidation of sulphur to sulphur dioxide, (ii) azoreductase triggered reduction of azobenzene to amino group or (iii) acid triggered reactions. Accordingly, hydrophobic segment of the amphiphile undergoes specific reaction triggered by one of the overexpressed cancer biomarkers and convert the hydrophobe into a hydrophile. This in turn converts the amphiphile into a hydrophile and leads to the disassembly of the nanostructure and permits the release of loaded drugs. Furthermore, the antisense DNA is conjugated to the hydrophobic segment through an imine bond, which also undergoes cleavage inside the cancer cells due to the acidic pH and leads to the simultaneous delivery of therapeutic DNA. Hence our strategy offers the fabrication of nanocarriers in a single step self-assembly process that exhibit (i) excellent biocompatibility, (ii) targeted delivery, (iii) synergistic therapeutic value, (iv) tumor environment stimuli-sensitive drug delivery and (v) cancer cell specific self-degradation.

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