Jeroen Johannes Lambertus Maria Cornelissen

Conversion of light into macroscopic helical motion

A key goal of nanotechnology is the development of artificial machines capable of converting molecular movement into macroscopic work. Although conversion of light into shape changes has been reported and compared to artificial muscles, real applications require work against an external load. Here, we describe the design, synthesis and operation of spring-like materials capable of converting light energy into mechanical work at the macroscopic scale. These versatile materials consist of molecular switches embedded in liquid-crystalline polymer springs. In these springs, molecular movement is converted and amplified into controlled and reversible twisting motions. The springs display complex motion, which includes winding, unwinding and helix inversion, as dictated by their initial shape. Importantly, they can produce work by moving a macroscopic object and mimicking mechanical movements, such as those used by plant tendrils to help the plant access sunlight. These functional materials have potential applications in micromechanical systems, soft robotics and artificial muscles.

Virus-based nanocarriers for drug delivery

New nanocarrier platforms based on natural biological building blocks offer great promises in revolutionalizing medicine. The usage of specific protein cage structures: virus-like particles (VLPs) for drug packaging and targetted delivery is summarized here. Versatile chemical and genetic modifications on the outer surfaces and inner cavities of VLPs facilitate the preparation of new materials that could meet the biocompatibility, solubility and high uptake efficiency requirements for drug delivery. A full evaluation on the toxicity, bio-distribution and immunology of these materials are envisaged to boost their application potentials.

Controlled encapsulation of multiple proteins in virus capsids.

Multiple proteins can be bound within the Cowpea Chlorotic Mottle Virus capsid shell in an efficient and controlled manner by using heterodimeric coiled-coil peptide oligomers. Through genetic modification, these oligomers can be attached to the capsid protein and an enhanced green fluorescent protein (EGFP). In this way, the capsid proteins can be noncovalently bound to EGFP prior to the induction of the capsid assembly. Up to 15 EGFP proteins can be encapsulated per capsid in a controlled and efficient manner.

Self-assembly and optically triggered disassembly of hierarchical dendron–virus complexes

Nature offers a vast array of biological building blocks that can be combined with synthetic materials to generate a variety of hierarchical architectures. Viruses are particularly interesting in this respect because of their structure and the possibility of them functioning as scaffolds for the preparation of new biohybrid materials. We report here that cowpea chlorotic mottle virus particles can be assembled into well-defined micrometre-sized objects and then reconverted into individual viruses by application of a short optical stimulus. Assembly is achieved using photosensitive dendrons that bind on the virus surface through multivalent interactions and then act as a molecular glue between the virus particles. Optical triggering induces the controlled decomposition and charge switching of dendrons, which results in the loss of multivalent interactions and the release of virus particles. We demonstrate that the method is not limited to the virus particles alone, but can also be applied to other functional protein cages such as magnetoferritin.

Polymersome stomatocytes:controlled shape transformation in polymer vesicles

We report here a controllable shape transformation of polymer vesicles (polymersomes) constructed from block copolymers of which the hydrophobic part is a high-molecular-weight glassy segment. Control over the shape transformation is obtained by kinetic manipulation of the phase behavior of this glassy hydrophobic segment. Kinetic manipulation of the phase behavior of polymer membranes allows for different shapes of polymersomes to be captured at specific times, which directly translates into physically robust nanostructures that are otherwise unobtainable. Combining the morphological diversity of giant liposomes and the physical robustness of polymersomes, our finding can be a general way to realize unusual nanostructures in a predictable manner.

Encapsulation of Phthalocyanine Supramolecular Stacks into Virus-like Particles

We report herein the encapsulation of a water-soluble phthalocyanine (Pc) into virus-like particles (VLPs) of two different sizes, depending on the conditions. At neutral pH, the cooperative encapsulation/templated assembly of the particles induces the formation of Pc stacks instead of Pc dimers, due to an increased confinement concentration. The Pc-containing VLPs may potentially be used as photosensitizer/vehicle systems for biomedical applications such as photodynamic therapy.

Polymeric Monosaccharide Receptors Responsive at Neutral pH

We present the first detailed report of the synthesis of Wulff-type styrenic monomers and their polymerization by radical addition-fragmentation chain transfer (RAFT) methods. The resulting polymers and block copolymers exhibit sugar-responsive solubilization in aqueous buffer solutions (pH = 7.4-7.8) in the presence of monosaccharides such as D-fructose and D-glucose.

Synthesis of polymer-biohybrids: from small to giant surfactants

Amphiphiles or surfactants, more popularly known as soaps, are among the oldest known chemical compounds used by man. Written text on a clay tablet dated to 2200 B.C. indicates that the Babylonians were familiar with soap-like substances. According to the Ebers papyrus (1550 B.C.), the ancient Egyptians bathed regularly in a mixture of animal oils, vegetable extracts, and alkaline salts, and a soap factory with bars of scented soap was found in the ruins of Pompeii (79 A.D.). In modern times, the use of soap has become universal, and we now understand reasonably well what happens when soap molecules are dispersed in aqueous solution and how the cleaning properties of soap work. The latter is related to the surface-active behavior of soap molecules, which is a result of their amphiphilic, also called amphipathic, character. Although the cleaning aspect is still an important issue, scientists are increasingly focusing on other properties of soaps, for example, self-assembling behavior and how this can be used in the design and non-covalent synthesis of new (macro)molecular architectures. These new molecules can be employed in nanotechnology and drug delivery, among other applications. This Account will focus on three different classes of amphiphiles. The first is the low molecular weight amphiphiles, also called classical amphiphiles in this context. A short overview will be given on the research carried out by our group and others on the self-assembly behavior and properties of these compounds; in particular, we focus on the ones that can be stabilized by polymerization (polymerized vesicles). Next, we will introduce the still relatively young field of superamphiphiles, macromolecules consisting of a hydrophobic and a hydrophilic polymeric block. Finally, and this constitutes the main part of this Account, we will provide an overview of a new class of amphiphiles, the so-called giant amphiphiles. These macromolecules have an enzyme or protein as the polar head group and a hydrophobic polymer as a tail. We will finish the Account with conclusions and an outlook to the future.

Single-Step Azide Introduction in Proteins via an Aqueous Diazo Transfer

The controlled introduction of azides in proteins provides targetable handles for selective protein manipulation. We present here an efficient diazo transfer protocol that can be applied in an aqueous solution, leading to the facile introduction of azides in the side chains of lysine residues and at the N-terminus of enzymes, e.g. horseradish peroxidase (HRP) and the red fluorescent protein DsRed. The effective introduction of azides was verified by mass spectrometry, after which the azido-proteins were used in Cu(I)-catalyzed [3 + 2] cycloaddition reactions. Azido-HRP retained its catalytic activity after conjugation of a small molecule. This modified protein could also be successfully immobilized on the surface of an acetylene-covered polymersome. Azido-DsRed was coupled to an acetylene-bearing protein allowing it to act as a fluorescent label, demonstrating the wide applicability of the diazo transfer procedure.

Application of Metal‐Free Triazole Formation in the Synthesis of Cyclic RGD–DTPA Conjugates

The tandem 1,3‐dipolar cycloaddition‐retro‐Diels–Alder (tandem crDA) reaction is presented as a versatile method for metal‐free chemoselective conjugation of a DTPA radiolabel to N‐δ‐azido‐cyclo(‐Arg‐Gly‐Asp‐d‐Phe‐Orn‐) via oxanorbornadiene derivatives. To this end, the behavior of several trifluoromethyl‐substituted oxanorbornadiene derivatives in the 1,3‐dipolar cycloaddition was studied and optimized to give a clean and efficient method for bio‐orthogonal ligation in an aqueous environment. After radioisotope treatment, the resulting 111In‐labeled c(RGD)‐CF3‐triazole‐DTPA conjugate was subjected to preliminary biological evaluation and showed high affinity for αvβ3 (IC50=192 nM) and favorable pharmacokinetics.