Nanocarriers Call the Last Shot in the Treatment of Brain Cancers

Abstract

Our brain is protected by physio-biological barriers. The blood–brain barrier (BBB) main mechanism of protection relates to the abundance of tight junctions (TJs) and efflux pumps. Although BBB is crucial for healthy brain protection against toxins, it also leads to failure in a devastating disease like brain cancer. Recently, nanocarriers have been shown to pass through the BBB and improve patients’ survival rates, thus becoming promising treatment strategies. Among nanocarriers, inorganic nanocarriers, solid lipid nanoparticles, liposomes, polymers, micelles, and dendrimers have reached clinical trials after delivering promising results in preclinical investigations. The size of these nanocarriers is between 10 and 1000 nm and is modified by surface attachment of proteins, peptides, antibodies, or surfactants. Multiple research groups have reported transcellular entrance as the main mechanism allowing for these nanocarriers to cross BBB. Transport proteins and transcellular lipophilic pathways exist in BBB for small and lipophilic molecules. Nanocarriers cannot enter via the paracellular route, which is limited to water-soluble agents due to the TJs and their small pore size. There are currently several nanocarriers in clinical trials for the treatment of brain cancer. This article reviews challenges as well as fitting attributes of nanocarriers for brain tumor treatment in preclinical and clinical studies.

Targeting the MUC1 tumor marker with an antibody improves the therapeutic efficacy of PEGylated liposomal doxorubicin in colon carcinoma.

“…When using targeting ligands, the fate of liposomes is influenced by factors such as the coupling method, the length and amount of PEG chains, and the surface charge of liposome (38,45). In fact, the physicochemical characteristics of particles affect longevity in the blood circulation (46,47). For instance, here we used PEGs with high molecular weights and the free PEG-NHS (not coupled to anti-MUC1 antibody), which facilitates in vivo tumor targeting (48).…”

Potential Medical Use of Fullerenols After Two Decades of Oncology Research

“…Initially, DOX was confirmed to be effective for a few types of tumors only, although it is now used in many treatments to stop the growth of cancer cells in bones, 93,94 liver, 97,102 prostate, 99,101 cervical tissue, 100 breasts, 87,89,95,96,98,108 pancreas, 86,103 lung, 99,104 ovarium, 105 colon, 106,107 and the brain. 92 Considering all the scientific evidence presented in this section, future research should focus on formulation improvement and the safety profile of the FRLs used as antioxidants to protect organs from toxicity in DOX-related treatments.…”

“… 86 - 108 Initially, DOX was confirmed to be effective for a few types of tumors only, although it is now used in many treatments to stop the growth of cancer cells in bones, 93 , 94 liver, 97 , 102 prostate, 99 , 101 cervical tissue, 100 breasts, 87 , 89 , 95 , 96 , 98 , 108 pancreas, 86 , 103 lung, 99 , 104 ovarium, 105 colon, 106 , 107 and the brain. 92 …”

The comparison of biodistribution of glutathione PEGylated nanoliposomal doxorubicin formulations prepared by pre‐insertion and post‐insertion methods for brain delivery in normal mice

“…Given the presence of glutathione receptors on the BBB, it stands to reason to use glutathione as a targeting ligand coupled with nanoliposomes [ 19 , 20 ]. GSH‐functionalised PEGylated liposomal DOX (2B3‐101) is a promising GSH‐targeted liposome which has finished the phase I/IIA clinical trial for the treatment of brain cancer, demonstrating that DOX can be administered more efficiently to brain tumours [ 21 , 22 ]. 2B3‐101 was prepared by incorporation of DSPE‐PEG2000‐Maleimide‐GSH into the existing product, Caelyx ® .…”