We review liposome-based delivery approaches that aim to address toxicities and to improve the therapeutic efficacy of mainstream chemotherapeutics, namely, doxorubicin, paclitaxel, and cisplatin. A brief review of the biomolecular mechanism(s) of action of these agents is followed by a description of characteristic examples of therapeutic approaches and of liposome membrane designs. Short reports on clinical studies are also included when applicable. The technical issues of different loading/encapsulation methods of these agents into liposomes are also discussed in terms of the physicochemical properties of both the agents themselves and of the lipid-based self-assemblies.
GALA-peptide is a random coil in neutral pH; in acidic pH, it becomes an amphipathic α-helix that aggregates in solution, possibly via its hydrophobic facet that runs along the helix's long axis. In the presence of fluid lipid membranes, the GALA-helix exhibits membrane-active properties that originate from the same hydrophobic facet; these properties make GALA a candidate for inclusion in drug delivery systems requiring permeation of the endosomal membrane to enable drug escape into the cytoplasm. Previous work has shown that the uniform functionalization of carrier nanoparticles with GALA-peptides improved their membrane activity and enhanced the endosomal escape of delivered therapeutics. The present study aims to evaluate the potential role of altering membrane activity via cluster-displayed GALA-peptides (for higher local valency) on the surface of carrier nanoparticles. The presentation of GALA-peptides on carrier nanoparticles was also designed to be pH-dependent. The peptide display on the surface of the carrier nanoparticles was uniform in neutral pH; in the acidic endosomal pH, the surface of nanocarriers formed domains (patches) with high local densities of GALA-peptides. The interactions between GALA-functionalized carrier nanoparticles and target lipid vesicles, utilized as endosome membrane surrogates that were used to primarily capture the fluid nature of these membranes, were studied as a function of pH. At endosomal pH values, ranging from 5.5 to 5.0, the greatest permeability of target membranes was induced by nanocarriers with clustered rather than uniformly displayed GALA. This enhancing effect had an optimum; at even more acidic pH values, too close an approximation of GALA-peptides residing within the same patches resulted in preferential intrapatch peptide interactions rather than interactions with the apposing target lipid membranes. This behavior could have the same physicochemical origin as the aforementioned GALA-peptide aggregation, observed in solution with decreasing pH at increasing peptide concentrations. The findings of this study support the potential of utilizing the clustered display of GALA-peptides on carrier nanoparticles to increase the permeation of fluid membranes used herein to capture this critical physical property of endosomal membranes and therefore to ultimately improve the endosomal escape of delivered therapeutics, enhancing therapeutic efficacy.
<div>AbstractSummary:<p>Published series on COVID-19 support the notion that patients with cancer are a particularly vulnerable population. There is a confluence of risk factors between cancer and COVID-19, and cancer care and treatments increase exposure to the virus and may dampen natural immune responses. The available evidence supports the conclusion that patients with cancer, in particular with hematologic malignancies, should be considered among the very high-risk groups for priority COVID-19 vaccination.</p></div>
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.