Multiwalled Nanotubes Formed by Catanionic Mixtures of Drug Amphiphiles

Mixing of oppositely charged amphiphilic molecules (catanionic mixing) offers an attractive strategy to produce morphologies different from those formed by individual molecules. We report here on the use of catanionic mixing of anticancer drug amphiphiles to construct multiwalled nanotubes containing a fixed and high drug loading. We found that the molecular mixing ratio, the solvent composition, the overall drug concentrations, as well as the molecular design of the studied amphiphiles are all important experimental parameters contributing to the tubular morphology. We believe these results demonstrate the remarkable potential that anticancer drugs could offer to self-assemble into discrete nanostructures and also provide important insight into the formation mechanism of nanotubes by catanionic mixtures. Our preliminary animal studies reveal that the CPT nanotubes show significantly prolonged retention time in the tumor site after intratumoral injection.

[1]  Bing Xu,et al.  Molecular hydrogels of therapeutic agents. , 2009, Chemical Society reviews.

[2]  Shiri Stempler,et al.  Self-assembled arrays of peptide nanotubes by vapour deposition. , 2009, Nature nanotechnology.

[3]  C. Tondre,et al.  Properties of the amphiphilic films in mixed cationic/anionic vesicles: a comprehensive view from a literature analysis. , 2001, Advances in colloid and interface science.

[4]  T. Ebbesen,et al.  Exceptionally high Young's modulus observed for individual carbon nanotubes , 1996, Nature.

[5]  D. Middleton,et al.  Insights into the Molecular Architecture of a Peptide Nanotube Using FTIR and Solid-State NMR Spectroscopic Measurements on an Aligned Sample** , 2013, Angewandte Chemie.

[6]  Ashutosh Chilkoti,et al.  Self-assembling chimeric polypeptide-doxorubicin conjugate nanoparticles that abolish tumors after a single injection , 2009, Nature materials.

[7]  Y. Talmon,et al.  Self‐Assembled Monodisperse Steroid Nanotubes in Water , 2002 .

[8]  Honggang Cui,et al.  Supramolecular nanostructures formed by anticancer drug assembly. , 2013, Journal of the American Chemical Society.

[9]  T. Fukushima,et al.  Self-Assembled Hexa-peri-hexabenzocoronene Graphitic Nanotube , 2004, Science.

[10]  D. Discher,et al.  Shape effects of filaments versus spherical particles in flow and drug delivery. , 2007, Nature nanotechnology.

[11]  Chaok Seok,et al.  Pulsating Tubules from Noncovalent Macrocycles , 2012, Science.

[12]  H. Cui,et al.  Supramolecular filaments containing a fixed 41% paclitaxel loading. , 2013, Chemical communications.

[13]  A. Aggeli,et al.  Self-assembling peptide nanotubes , 2008 .

[14]  Juan R. Granja,et al.  Self-assembling organic nanotubes based on a cyclic peptide architecture , 1994, Nature.

[15]  R. Mezzenga,et al.  Polymorphism complexity and handedness inversion in serum albumin amyloid fibrils. , 2013, ACS nano.

[16]  C. Contag,et al.  Overcoming multidrug resistance of small-molecule therapeutics through conjugation with releasable octaarginine transporters , 2008, Proceedings of the National Academy of Sciences.

[17]  Ehud Gazit,et al.  Self-assembled peptide nanostructures: the design of molecular building blocks and their technological utilization. , 2007, Chemical Society reviews.

[18]  M. Kirschner,et al.  Dynamic instability of microtubule growth , 1984, Nature.

[19]  Bing Xu,et al.  Versatile small-molecule motifs for self-assembly in water and the formation of biofunctional supramolecular hydrogels. , 2011, Langmuir : the ACS journal of surfaces and colloids.

[20]  Stuart R Stock,et al.  Bone regeneration mediated by biomimetic mineralization of a nanofiber matrix. , 2010, Biomaterials.

[21]  Andrew M. Smith,et al.  Designing peptide based nanomaterials. , 2008, Chemical Society reviews.

[22]  S. Stupp,et al.  Coassembled cytotoxic and pegylated peptide amphiphiles form filamentous nanostructures with potent antitumor activity in models of breast cancer. , 2012, ACS nano.

[23]  E. W. Meijer,et al.  Functional Supramolecular Polymers , 2012, Science.

[24]  N. Clark,et al.  Lipid Tubule Self-Assembly: Length Dependence on Cooling Rate Through a First-Order Phase Transition , 1995, Science.

[25]  Giovanni Dietler,et al.  Measurement of intrinsic properties of amyloid fibrils by the peak force QNM method. , 2012, Nanoscale.

[26]  S. Stupp,et al.  Coassembly of amphiphiles with opposite peptide polarities into nanofibers. , 2005, Journal of the American Chemical Society.

[27]  M. Ghadiri,et al.  Design of self-assembling peptide nanotubes with delocalized electronic states. , 2006, Small.

[28]  S. Magdassi,et al.  Drug-loaded nanoparticles and supramolecular nanotubes formed from a volatile microemulsion with bile salt derivatives. , 2013, Physical chemistry chemical physics : PCCP.

[29]  T. Fukushima,et al.  Supramolecular Linear Heterojunction Composed of Graphite-Like Semiconducting Nanotubular Segments , 2011, Science.

[30]  Honggang Cui,et al.  Elucidating the assembled structure of amphiphiles in solution via cryogenic transmission electron microscopy. , 2007, Soft matter.

[31]  Robert A. Grothe,et al.  Structure of the cross-beta spine of amyloid-like fibrils. , 2005, Nature.

[32]  Robert Schlögl,et al.  Surface-Modified Carbon Nanotubes Catalyze Oxidative Dehydrogenation of n-Butane , 2008, Science.

[33]  I. Hamley,et al.  Coassembly in binary mixtures of peptide amphiphiles containing oppositely charged residues. , 2013, Langmuir : the ACS journal of surfaces and colloids.

[34]  G. Liang,et al.  Folic acid as a versatile motif to construct molecular hydrogelators through conjugations with hydrophobic therapeutic agents , 2012 .

[35]  V. Conticello,et al.  Exploiting amyloid fibril lamination for nanotube self-assembly. , 2003, Journal of the American Chemical Society.

[36]  H. Cui,et al.  Synthesis and Self-Assembly of a Mikto-Arm Star Dual Drug Amphiphile Containing both Paclitaxel and Camptothecin. , 2014, Journal of materials chemistry. B.

[37]  R. Mezzenga,et al.  Direct observation of time-resolved polymorphic states in the self-assembly of end-capped heptapeptides. , 2011, Angewandte Chemie.

[38]  Peter Beike,et al.  Intermolecular And Surface Forces , 2016 .

[39]  I. Hamley,et al.  Nanoshells and nanotubes from block copolymers. , 2005, Soft matter.

[40]  R. Mezzenga,et al.  Proteins Fibrils from a Polymer Physics Perspective , 2012 .

[41]  Shaoyi Jiang,et al.  Ultralow‐Fouling, Functionalizable, and Hydrolyzable Zwitterionic Materials and Their Derivatives for Biological Applications , 2010, Advanced materials.

[42]  Jonathan V Selinger,et al.  Theory of Self-Assembled Tubules and Helical Ribbons , 2001 .

[43]  Gulik-Krzywicki,et al.  Self-assembly of flat nanodiscs in salt-free catanionic surfactant solutions , 1999, Science.

[44]  Prost,et al.  Intrinsic bending force in anisotropic membranes made of chiral molecules. , 1988, Physical review. A, General physics.

[45]  Paul Yager,et al.  Formation of Tubules by a Polymerizable Surfactant , 1984 .

[46]  I. Manners,et al.  Nanotubes from the self-assembly of asymmetric crystalline-coil poly(ferrocenylsilane-siloxane) block copolymers. , 2002, Journal of the American Chemical Society.

[47]  J. Schnur,et al.  Lipid Tubules: A Paradigm for Molecularly Engineered Structures , 1993, Science.

[48]  H. Cui,et al.  Linker-determined drug release mechanism of free camptothecin from self-assembling drug amphiphiles. , 2014, Chemical communications.

[49]  R. Mezzenga,et al.  Adjustable twisting periodic pitch of amyloid fibrils , 2011 .

[50]  J. Schneider,et al.  Self-assembling materials for therapeutic delivery. , 2009, Acta biomaterialia.

[51]  R. Mezzenga,et al.  Correlation between nanomechanics and polymorphic conformations in amyloid fibrils. , 2014, ACS nano.

[52]  S. Raghavan,et al.  Unraveling the mechanism of nanotube formation by chiral self-assembly of amphiphiles. , 2011, Journal of the American Chemical Society.

[53]  A. Mehta,et al.  Peptides organized as bilayer membranes. , 2010, Angewandte Chemie.

[54]  Toshimi Shimizu,et al.  Supramolecular nanotube architectures based on amphiphilic molecules. , 2005, Chemical reviews.

[55]  J. Zasadzinski,et al.  Phase behavior and structures of mixtures of anionic and cationic surfactants , 1992 .

[56]  R. Mezzenga,et al.  Towards lysozyme nanotube and 3D hybrid self-assembly. , 2013, Nanoscale.

[57]  Ali Hossain Khan,et al.  Vesicle Formation and General Phase Behavior in the Catanionic Mixture SDS−DDAB−Water. The Anionic-Rich Side , 1998 .

[58]  Guojun Liu,et al.  Block Copolymer Nanotubes. , 2000, Angewandte Chemie.

[59]  S. Iijima.  Helical microtubules of graphitic carbon , 1991, Nature.

[60]  P. Messersmith,et al.  Chiral Self-Assembly of Nanotubules and Ribbons from Phospholipid Mixtures , 2001 .

[61]  Matthew Tirrell,et al.  Bottom-up design of biomimetic assemblies. , 2004, Advanced drug delivery reviews.

[62]  S. Stupp,et al.  Molecular crystallization controlled by pH regulates mesoscopic membrane morphology. , 2012, ACS nano.

[63]  H. Hägerstrand,et al.  Microtubes and nanotubes of a phospholipid bilayer membrane , 2002 .

[64]  C. Leggio,et al.  Catanionic tubules with tunable charge. , 2010, Angewandte Chemie.

[65]  Ruth Duncan,et al.  Polymer conjugates as anticancer nanomedicines , 2006, Nature Reviews Cancer.

[66]  I. Hamley.  Peptide nanotubes. , 2014, Angewandte Chemie.

[67]  Thomas Zemb,et al.  Self-assembly of regular hollow icosahedra in salt-free catanionic solutions , 2001, Nature.