Efficacious Doxorubicin Delivery Using Glutathione‐Responsive Hollow Non‐phospholipid Vesicles Bearing Lipoyl Cholesterols

Abstract

In this study, we developed redox‐sensitive vesicles using synthesised lipoyl cholesterol derivatives, a non‐ionic surfactant and an optimum level of free cholesterol. Interestingly, concentration‐dependent self‐assembly was observed by scanning electron microscopy, wherein vesicles manifested as hollow spherical (at 0.15 mm) and triangular (0.50 mm). The redoxresponsive characteristics of the vesicles was probed in the presence of dithiothreitol; they underwent a clear increase in size as observed by dynamic light scattering measurements. These vesicles could easily encapsulate an anticancer drug, doxorubicin, and were observed to be stable in the presence of serum. They showed substantial release of the drug in response to biologically relevant stimulus, that is, glutathione. A toxicity assessment on HeLa and HepG2 cancer cells demonstrated activities of the drug‐loaded vesicles comparable to that of free drug, whereas significantly enhanced toxicity and apoptotic induction were observed against drug‐resistant HeLa cells, which was determined by studying the cellular internalisation of doxorubicin.

Harnessing Endogenous Stimuli for Responsive Materials in Theranostics

“…217 In an A2780cis tumor-bearing mouse model of resistant ovarian cancer, the particles reduced tumor growth significantly, which the authors ascribe to the combined effect of intracellular prodrug activation and also the associated minimization of active glutathione, which can reduce the pharmacological activity of cisplatin. Interestingly, there are also numerous examples of disulfide units being incorporated into a range of biological materials, from peptides 218,219 and lipid materials 220 to the natural polymers alginate and hydroxyethyl starch. 221,222 In comparison to reduction-sensitive constructs, oxidationsensitive materials have applications mostly in inflammation and target oxidative stress, although both involve manipulation of redox homeostasis.…”