Abstract
Chemotherapy is one of the most effective treatments for cancer. However, intracellular delivery of many anticancer drugs is hindered by their hydrophobicity and low molecular weight. Here, we describe highly biocompatible and biodegradable amphiphilic vitamin conjugates comprising hydrophobic vitamin E and hydrophilic vitamin B labeled with dual pH and glutathione-responsive degradable linkages. Vitamin-based micelles (vitamicelles), formed by self-assembly in aqueous solutions, were optimized based on their stability after encapsulation of doxorubicin (DOX). The resulting vitamicelles have great potential as vehicles for anticancer drugs because they show excellent biocompatibility (>94% after 48 h of incubation) and rapid biodegradability (>90% after 2.5 h). Compared with free DOX, DOX-loaded vitamicelles showed a markedly enhanced anticancer effect as they released the drug rapidly and inhibited drug efflux out of cells efficiently. By exploiting these advantages, this study not only provides a promising strategy for circumventing existing challenges regarding the delivery of anticancer drugs but also extends the utility of current DOX-induced chemotherapy.
Highlights
Chemotherapy uses anticancer drugs to destroy or inhibit the growth of cancer cells.It is one of the most effective treatments that improve cancer survival, and it can be given before and/or after surgery, either alone or in combination with other treatments, such as hormones [1], radiation [2], and immunotherapy [3]
The population of dead cells showed a positive association with cytotoxicity in together, these results demonstrate that DL-SS-MC has great potential to circumvent the both cancer cell lines (Figure 5e,f)
The hydrodynamic diameter of vitamicelles was measured by dynamic light scattering (DLS; ELSZ-1000; Otsuka Electronics, Osaka, Japan), and the morphology and core size of the vitamicelles were observed by field-emission transmission electron microscopy (FE-TEM; JEOL 2100F; Tokyo, Japan)
Summary
Chemotherapy uses anticancer drugs to destroy or inhibit the growth of cancer cells. It is one of the most effective treatments that improve cancer survival, and it can be given before and/or after surgery, either alone or in combination with other treatments, such as hormones [1], radiation [2], and immunotherapy [3]. Various VB-modified materials are internalized into cancer cells through the VTC-mediated pathway [28,29,30] Based on these compelling characteristics, we selected VE and VB as the main components of our drug carrier; these were linked covalently to obtain amphiphilic conjugates (Figure 1). The tumor microenvironment is more acidic than the rest of the body [31]; the GSH concentration in cancer cells is much higher than that in normal cells [32] Such significant variations in pH and GSH levels are utilized to promote tumor-specific drug release by vitamicelles, thereby minimizing any toxic side effects.
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