ABSTRACT
A cellular protease (furin)-mediated graphene-based nanosystem is developed for co-delivery of a membrane-associated cytokine (tumor-necrosis-factor-related apoptosis-inducing ligand, TRAIL) and an intracellular-acting small-molecule drug (Doxorubicin, DOX). TRAIL and DOX can be sequentially released toward the plasma membrane and nucleus, respectively.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Furin/metabolism , Graphite/chemistry , Nanocapsules/chemistry , Neoplasms, Experimental/drug therapy , Peptides/pharmacokinetics , Antineoplastic Combined Chemotherapy Protocols/chemistry , Apoptosis/drug effects , Cell Line, Tumor , Cytokines/administration & dosage , Cytokines/chemistry , Diffusion , Doxorubicin/administration & dosage , Doxorubicin/chemistry , Humans , Nanocapsules/administration & dosage , Nanocapsules/ultrastructure , Neoplasms, Experimental/pathology , Oxides/chemistry , Particle Size , Polyethylene Glycols/chemistry , TNF-Related Apoptosis-Inducing Ligand/administration & dosage , TNF-Related Apoptosis-Inducing Ligand/chemistry , Treatment OutcomeABSTRACT
A significant problem affecting electrospun nanofibrous tissue scaffolds is poor infiltration of cells into their three-dimensional (3D) structure. Environmental and physical manipulation, however, can enhance cellular infiltration into electrospun scaffolds. In this work, RGD-modified alginate mats with increased thickness and porosity were achieved by pairing high humidity electrospinning with post-processing ultra-sonication. RGD-modified alginate, polyethylene oxide (PEO), and an FDA-approved, nonionic surfactant blends were electrospun in 20 and 50% relative humidity conditions. Mats electrospun in high humidity conditions resulted in significantly increased mat thickness and decreased fiber diameters. The mats' alginate content was then isolated via ionic crosslinking and PEO/surfactant extraction. Finally, the alginate-only mat was post-processed by ultra-sonication to further enhance its cross-sectional thickness. Cell morphology, proliferation, and infiltration into the scaffolds were evaluated by seeding fibroblasts onto the alginate mat. Cell spreading, growth and infiltration improved with increased humidity and ultra-sonication. This approach shows great promise for the design of cell-permeable nanofibrous scaffolds for tissue-engineering applications.