An official website of the United States government
Nano-formulated, combinatory therapeutics that control the spatiotemporal aspects of drug release have potential to overcome many of the challenges faced in cancer therapy. Herein, we describe a peptide nanotube functionalized with two anticancer drugs, 5-fluoruracil (5-FU) and camptothecin (CPT). The nanotube was formed via peptide self-assembly, which positioned 5-FU on the surface at the aqueous interface; whereas, CPT was sequestered within the hydrophobic walls. Thus, two different release profiles were observed: rapid release of 5-FU, followed by slower, sustained production of CPT. This profile emerged from the rapid hydrolytic cleavage of 5-FU at the aqueous/nanotube interface, which produced a smaller nanotube comprised of the peptide fragment.
more »
« less
Self-assembly of a robust, reduction-sensitive camptothecin nanotube
The self-assembly and covalent crosslinking of a camptothecin (CPT) tetrapeptide nanotube is reported. Intermolecular disulfide bond formation of a self-assembled CPT-peptide reversibly stabilized the nanotubes toward dissociation at low concentrations, resulting in inhibited release of CPT. In the presence of dithiothreitol (DTT), the release of CPT was significantly accelerated. The crosslinked nanotubes also exhibited in vitro cytotoxicity against human non-small cell lung cancer cell lines A549 and H460.
more »
« less
- Award ID(s):
- 1708390
- PAR ID:
- 10224855
- Date Published:
- Journal Name:
- Chemical Communications
- Volume:
- 56
- Issue:
- 71
- ISSN:
- 1359-7345
- Page Range / eLocation ID:
- 10337 to 10340
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
null (Ed.)The self-assembly of 5-fluorouracil dilysine conjugates into self-supporting hydrogels, comprised of entangled nanofibers or rigid nanotubes with diameters of 10 and 16 nm, respectively, is reported. The rate of release of 5-Fu from the conjugates was highly dependent on concentration in solution, whereas, release from the fully formed hydrogels was significantly slower. The 5-Fu conjugate also exhibited promising in vitro cytotoxicity against human tumor cell lines A549, H460 and H23.more » « less
-
This Work-in-Progress research paper focuses on the game-based learning environment of GeoExplorer, a digital learning tool that simulates Cone Penetration Testing (CPT) – a field test that civil engineers conduct to understand soil properties. This paper aims to investigate the gendered patterns of student interaction with GeoExplorer, if any, and the associated gendered patterns of content comprehension and self-efficacy related to one's ability to pursue CPT in the field, if any. As such, we ask: (1) How, if at all, does gender affect a student's belief in their ability to apply skills gained through engagement with GeoExplorer in real world environments? and (2) How, if at all, do prior gaming experience and gender impact the GeoExplorer play experience? Four open-ended semi-structured interviews regarding students' experience with gameplay, gender identity, and learning were analyzed. Preliminary analyses used narrative and grounded theory approaches. Our early findings indicate a lack of student insight on the role of their gender identity on their gameplay experience and the presence of a gendered impact of gameplay on student learning and self-efficacy in carrying out CPT in the field.more » « less
-
Janus base nanotubes are novel, self-assembled nanomaterials. Their original designs were inspired by DNA base pairs, and today a variety of chemistries has developed, distinguishing them as a new family of materials separate from DNA origami, carbon nanotubes, polymers, and lipids. This review article covers the principal examples of self-assembled Janus base nanotubes, which are driven by hydrogen-bond and π-π stacking interactions in aqueous environments. Specifically, self-complementary hydrogen bonds organize molecules into ordered arrays, forming macrocycles, while π-π interactions stack these structures to create tubular forms. This review elucidates the molecular interactions that govern the assembly of nanotubes and advances our understanding of nanoscale self-assembly in water.more » « less
-
null (Ed.)Tandem repeat proteins exhibit native designability and represent potentially useful scaffolds for the construction of synthetic biomimetic assemblies. We have designed 2 synthetic peptides, HEAT_R1 and LRV_M3Δ1, based on the consensus sequences of single repeats of thermophilic HEAT (PBS_HEAT) and Leucine-Rich Variant (LRV) structural motifs, respectively. Self-assembly of the peptides afforded high-aspect ratio helical nanotubes. Cryo-electron microscopy with direct electron detection was employed to analyze the structures of the solvated filaments. The 3D reconstructions from the cryo-EM maps led to atomic models for the HEAT_R1 and LRV_M3Δ1 filaments at resolutions of 6.0 and 4.4 Å, respectively. Surprisingly, despite sequence similarity at the lateral packing interface, HEAT_R1 and LRV_M3Δ1 filaments adopt the opposite helical hand and differ significantly in helical geometry, while retaining a local conformation similar to previously characterized repeat proteins of the same class. The differences in the 2 filaments could be rationalized on the basis of differences in cohesive interactions at the lateral and axial interfaces. These structural data reinforce previous observations regarding the structural plasticity of helical protein assemblies and the need for high-resolution structural analysis. Despite these observations, the native designability of tandem repeat proteins offers the opportunity to engineer novel helical nanotubes. Moreover, the resultant nanotubes have independently addressable and chemically distinguishable interior and exterior surfaces that would facilitate applications in selective recognition, transport, and release.more » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/d0cc03528a
