ABSTRACT
BACKGROUND: A large number of studies have been conducted on the treatment of glioblastoma multiforme (GBM). Chemotherapeutic drugs cannot penetrate deeply into the brain parenchyma due to the presence of the blood-brain barrier (BBB). Hence, crossing BBB is a significant obstacle in developing new therapeutic methods for GBM. OBJECTIVE: Cell-penetrating peptides (CPPs) have emerged as new tools that can efficiently deliver various substances across BBB. CPPs beneficial properties, such as BBB penetration capacity, low toxicity, and the ability to achieve active targeting and controllable drug release, have made them worthy candidates for GBM treatment. However, their application is limited by several drawbacks, including lack of selectivity, insufficient transport efficacy, and low stability. In order to overcome the selectivity issue, tumor targeting peptides and sequences that can be activated at the target site have been embedded into the structure of CPPs. To overcome their insufficient transport efficacy into the cells, which is mostly due to endosomal entrapment, various endosomolytic moieties have been incorporated into CPPs. Finally, their instability in blood circulation can be solved through different modifications to their structures. As this field is moving beyond preclinical studies, the discovery of new and more efficient CPPs for GBM treatment has become crucial. Thus, by using display techniques, such as phage display, this encouraging treatment strategy can be developed further. CONCLUSION: Consequently, despite several challenges in CPPs application, recent progress in studies has shown their potential for the development of the next generation GBM therapeutics.
Subject(s)
Brain Neoplasms , Cell-Penetrating Peptides , Glioblastoma , Blood-Brain Barrier , Brain Neoplasms/drug therapy , Cell-Penetrating Peptides/chemistry , Drug Delivery Systems/methods , Glioblastoma/drug therapy , HumansABSTRACT
We report a label-free electrochemical aptamer-based biosensor for the detection of human prostate-specific antigen (PSA). The thiolate DNA aptamer against PSA was conjugated to the reduced graphene oxide/Au (RGO-Au) nanocomposite through the self-assembly of Au-S groups. Owing to the large volume to surface ratio, the RGO-Au nanocomposite provides a large surface for aptamer loading. The RGO-Au/aptamer was combined with a Nafion polymer and immobilized on a glassy carbon electrode. The interaction of aptamer with PSA was studied by cyclic voltammetry, square wave voltammetry, and electrochemical impedance spectroscopy. The detection of limit for prepared electrode was obtained about 50 pg/mL at the potential of 0.4 V in potassium hexacyanoferrate [K4 Fe(CN)6 ] medium. To decrease the limit of detection (LOD) and applied potential of the prepared nanoprobe Cu/carbon quantum dots (CuCQD) is introduced as a new redox. The results show that this new electrochemical medium provides better conditions for the detection of PSA. LOD of a nanoprobe in CuCQD media was obtained as 40 pg/mL at the potential of -0.2 V. Under optimal conditions, the aptasensor exhibits a linear response to PSA with a LOD as small as 3 pg/mL. The present aptasensor is highly selective and sensitive and shows satisfactory stability and repeatability.
Subject(s)
Aptamers, Nucleotide , Biosensing Techniques , Graphite , Nanocomposites , Prostate-Specific Antigen , Quantum Dots , Humans , Male , Aptamers, Nucleotide/chemistry , Biosensing Techniques/methods , Carbon , Electrochemical Techniques/methods , Electrodes , Gold/chemistry , Graphite/chemistry , Limit of Detection , Prostate-Specific Antigen/analysis , Quantum Dots/chemistryABSTRACT
Over recent years, many different nanoparticle-based drug delivery systems (NDDSs) have been developed. Recently the development of stimulus-responsive NDDSs has come into sharper focus. Carbon dots (CDs) possess outstanding features such as useful optical properties, good biocompatibility, and the ability for easy surface modification. Appropriate surface modification can allow these NDDSs to respond to various chemical or physical stimuli that are characteristic of their target cells or tissue (frequently malignant cells or tumors). The present review covers recent developments of CDs in NDDSs with a particular focus on internal stimulus response capability that allows simultaneous imaging and therapeutic delivery (theranostics). Relevant stimuli associated with tumor cells and tumors include pH levels, redox potential, and different enzymatic activities can be used to activate the CDs at the desired sites.
