Cyclic peptide-poly(HPMA) nanotubes as drug delivery vectors: In vitro assessment, pharmacokinetics and biodistribution

Abstract

Size and shape have progressively appeared as some of the key factors influencing the properties of nanosized drug delivery systems. In particular, elongated materials are thought to interact differently with cells and therefore may allow alterations of in vivo fate without changes in chemical composition. A challenge, however, remains the creation of stable self-assembled materials with anisotropic shape for delivery applications that still feature the ability to disassemble, avoiding organ accumulation and facilitating clearance from the system. In this context, we report on cyclic peptide-polymer conjugates that self-assemble into supramolecular nanotubes, as confirmed by SANS and SLS. Their behaviour ex and in vivo was studied: the nanostructures are non-toxic up to a concentration of 0.5 g L and cell uptake studies revealed that the pathway of entry was energy-dependent. Pharmacokinetic studies following intravenous injection of the peptide-polymer conjugates and a control polymer to rats showed that the larger size of the nanotubes formed by the conjugates reduced renal clearance and elongated systemic circulation. Importantly, the ability to slowly disassemble into small units allowed effective clearance of the conjugates and reduced organ accumulation, making these materials interesting candidates in the search for effective drug carriers.

Low‐Fouling Fluoropolymers for Bioconjugation and In Vivo Tracking

“…It is widely appreciated that decoration of therapeutic molecules with low-fouling polymers can dramatically improve their bioavailability in the form of increased stability, solubility,a nd pharmacokinetics.Arange of polymers have been used for this purpose and have facilitated the development of advanced (nano)medicines for more precise and effective treatment of diseases. [1] With all of these molecular and nanoparticles entities,i ti si mportant to be able to measure,inafacile manner, the in vivo location and concentration of the polymer-conjugated therapeutics after administration. Such information is closely related to the therapeutic outcome.T ypically,t his can be achieved by additionally conjugating imaging moieties such as fluorophores, [2] paramagnetic contrast agents (CAs), [3] or radioactive isotopes.…”

Dual self-assembly of supramolecular peptide nanotubes to provide stabilisation in water

“…As a motif to form supramolecular polymers, hydrogen bonded core-stacking moiety have gained much attention due to their ability to form directional nanostructures 18–21 . The ease in functionalising these cores with a range of different substituents, such as polymers 22 , dyes 23 or drugs 16 , make them ideal candidates for bioactive materials such as antimicrobials 24 or drug delivery vectors 15 . The most prominent example of hydrogen bonded self-assemblies are peptides.…”

“…The attachment of hydrophilic polymers to the periphery of the peptide core has been studied to provide water soluble aggreates 22,34,35 . More recently, they have been shown to be pH and redox responsive 36 , have antimicrobial activity 24,37 and be a promising drug carrier 15,16 .…”

Peptide Nanotube‐Templated Biomineralization of Cu2−xS Nanoparticles for Combination Treatment of Metastatic Tumor

“…For instance, the collagen fiber‐mimicking supramolecular assembles of the peptide templates exhibit increased aspect ratio than that of the nanospheres, and they possess the potential to construct aligned and tunable functional materials by varying the parameters correlated with the kinetics and thermodynamics of assembly . Importantly, the elongated peptide nanostructures display improved tissue adhesion, increased cellular uptake, and elongated blood circulation in comparison with their spherical counterpart . Additionally, further surface modification is facile for achieving desired multifunctionality.…”