A Novel pH-Tunable Secondary Conformation Containing Mixed Micellar System in Anticancer Treatment

Abstract

In this study, for the first time, we precisely assembled the poly-γ-benzyl-l-glutamate and an amphiphilic copolymer d-α-tocopherol polyethylene glycol succinate into a mixed micellar system for the embedment of the anticancer drug doxorubicin. Importantly, the intracellular drug-releasing behaviors could be controlled by changing the secondary structures of poly-γ-benzyl-l-glutamate via the precise regulation of the buffer’s pH value. Under neutral conditions, the micellar architectures were stabilized by both α-helix secondary structures and the microcrystalline structures. Under acidic conditions (pH 4.0), the interior structures transformed into a coil state with a disordered alignment, inducing the release of the loaded drug. A remarkable cytotoxicity of the Dox-loaded mixed micelles was exhibited toward human lung cancer cells in vitro. The internalizing capability into the cancer cells, as well as the intracellular drug-releasing behaviors, were also identified and observed. The secondary structures containing Dox-loaded mixed micelles had an outstanding antitumor efficacy in human lung cancer A549 cells-bearing nude mice, while little toxicities occurred or interfered with the hepatic or renal functions after the treatments. Thus, these pH-tunable α-helix-containing mixed micelles are innovative and promising for controlled intracellular anticancer drug delivery.

Stimuli-Responsive Drug Delivery Systems for the Diagnosis and Therapy of Lung Cancer

“…The poly-γ-benzyl-l-glutamate and an amphiphilic copolymer d-α-tocopherol polyethylene glycol succinate mixed micellar system could control the release of DOX by changing the secondary structures of poly-γ-benzyl-l-glutamate. The DOX-loaded mixed micelles exhibited great anti-tumor efficacy in human lung cancer A549 cells-bearing nude mice [ 63 ].…”

Self‐Assembly of Poly(Amino Acid)s Mediated by Secondary Conformations

“…[32,33,34] Among them, poly(amino acid)s (PAAs) have received widespread attention due to their simple and controllable synthesis, good biocompatibility and nontoxic metabolized products, flexible and adjustable functions, as well as the ability to fold into stable secondary structures. [35,36] Additionally, with the development of N-carboxyanhydrides (NCA) ring-opening polymerization (ROP) technology, [37,38] significant progress has been made in the regulation of secondary conformations of PAAs in recent years. [16,30] PAAs have been extensively studied as structural or functional materials such as nanoparticles, nanotubes, and hydrogels.…”

Cancer Nanomedicine

“…Within this Special Issue, a diverse range of cancer nanomedicines have been discussed, including the more traditional organic-based systems, such as lipid [ 1 , 2 , 3 , 4 , 5 , 6 ], polymer [ 7 , 8 , 9 , 10 , 11 ] and cyclodextrin-based [ 12 ] particulates. Additionally, there are multiple studies from the growing area of inorganic systems, such as carbon nanomaterials (such as graphene oxide [ 13 , 14 ] and carbon nanotubes [ 15 ]) as well as other more established metallic nanomaterials, such as gold [ 16 , 17 ], iron oxide [ 18 , 19 ] and silica-based [ 20 , 21 ] systems.…”

“…As the science develops and leads us down new avenues, the findings and their meaning are closely scrutinised and debated within the community. This issue includes 32 scientific manuscripts, 13 review articles and 1 case report reflecting the hot topics within this area [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ].…”