Abstract
Nanocarriers are delivery platforms of drugs, peptides, nucleic acids and other therapeutic molecules that are indicated for severe human diseases. Gliomas are the most frequent type of brain tumor, with glioblastoma being the most common and malignant type. The current state of glioma treatment requires innovative approaches that will lead to efficient and safe therapies. Advanced nanosystems and stimuli-responsive materials are available and well-studied technologies that may contribute to this effort. The present study deals with the development of functional chimeric nanocarriers composed of a phospholipid and a diblock copolymer, for the incorporation, delivery and pH-responsive release of the antiglioma agent TRAM-34 inside glioblastoma cells. Nanocarrier analysis included light scattering, protein incubation and electron microscopy, and fluorescence anisotropy and thermal analysis techniques were also applied. Biological assays were carried out in order to evaluate the nanocarrier nanotoxicity in vitro and in vivo, as well as to evaluate antiglioma activity. The nanosystems were able to successfully manifest functional properties under pH conditions, and their biocompatibility and cellular internalization were also evident. The chimeric nanoplatforms presented herein have shown promise for biomedical applications so far and should be further studied in terms of their ability to deliver TRAM-34 and other therapeutic molecules to glioblastoma cells.
Highlights
One of the main obstacles to solid tumor therapy is the poor pharmacokinetics of drug molecules [1]
Two types of probes were utilized. 1,6-diphenyl-1,3,5-hexatriene (DPH) is a non-polar molecule that is incorporated inside the hydrophobic region of the liposome bilayer with its long axis parallel to the acyl chains, whereas 1-[4-(trimethyl-ammonium) phenyl]-6-phenyl-1,3,5hexatriene (TMA-DPH) is anchored onto the bilayer, with its positively charged amino groups in contact with the medium water molecules [26]
These two molecules allow for evaluation of the mobility of both the hydrophobic and the hydrophilic regions of the membrane, offering a complete picture of the membrane order at different depths of the bilayer [26]
Summary
One of the main obstacles to solid tumor therapy is the poor pharmacokinetics of drug molecules [1]. After a stimuli-responsive nanocarrier reaches to the tumor site, it responds to the extracellular and/or intracellular environments, releasing the incorporated bioactive substance in specific tissues or cell compartments, and at a specific rate. This utility is designed based on the deviant physiological conditions that exist inside a tumor, compared with healthy tissues [2]. These nanocarriers are defined as “functional” and “smart” advanced drug delivery nanosystems (aDDnSs) and are very promising vehicles for co-delivering diagnostic and therapeutic agents [3,4]. Frequent recurrences and short survival have led to a demand for new and innovative therapeutic approaches for this difficult and complex disease [5,6]
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