Tailored Multivalent Targeting of Siglecs with Photosensitizing Liposome Nanocarriers.

The modification of surfaces with multiple ligands allows the formation of platforms for the study of multivalency in diverse processes. Herein we use this approach for the implementation of a photosensitizer (PS)-nanocarrier system that binds efficiently to siglec-10, a member of the CD33 family of siglecs (sialic acid (SA)-binding immunoglobulin-like lectins). In particular, a zinc phthalocyanine derivative bearing three SA moieties (PcSA) has been incorporated in the membrane of small unilamellar vesicles (SUVs), retaining its photophysical properties upon insertion into the SUV's membrane. The interaction of these biohybrid systems with human siglec-10-displaying supported lipid bilayers (SLBs) has shown the occurrence of weakly multivalent, superselective interactions between vesicle and SLB. The SLB therefore acts as an excellent cell membrane mimic, while the binding with PS-loaded SUVs shows the potential for targeting siglec-expressing cells with photosensitizing nanocarriers.

Porphyrinoid biohybrid materials as an emerging toolbox for biomedical light management.

The development of photoactive and biocompatible nanomaterials is a current major challenge of materials science and nanotechnology, as they will contribute to promoting current and future biomedical applications. A growing strategy in this direction consists of using biologically inspired hybrid materials to maintain or even enhance the optical properties of chromophores and fluorophores in biological media. Within this area, porphyrinoids constitute the most important family of organic photosensitizers. The following extensive review will cover their incorporation into different kinds of photosensitizing biohybrid materials, as a fundamental research effort toward the management of light for biomedical use, including technologies such as photochemical internalization (PCI), photoimmunotherapy (PIT), and theranostic combinations of fluorescence imaging and photodynamic therapy (PDT) or photodynamic inactivation (PDI) of microorganisms.

Photoantimicrobial Biohybrids by Supramolecular Immobilization of Cationic Phthalocyanines onto Cellulose Nanocrystals.

The development of photoactive and biocompatible nanostructures is a highly desirable goal to address the current threat of antibiotic resistance. Here, we describe a novel supramolecular biohybrid nanostructure based on the non-covalent immobilization of cationic zinc phthalocyanine (ZnPc) derivatives onto unmodified cellulose nanocrystals (CNC), following an easy and straightforward protocol, in which binding is driven by electrostatic interactions. These non-covalent biohybrids show strong photodynamic activity against S. aureus and E. coli, representative examples of Gram-positive and Gram-negative bacteria, respectively, and C. albicans, a representative opportunistic fungal pathogen, outperforming the free ZnPc counterparts and related nanosystems in which the photosensitizer is covalently linked to the CNC surface.

The systems perspective at the crossroads between chemistry and biology.

During the last century a number of authors pointed to the inherently systemic and dynamic nature of the living, yet their message was largely ignored by the mainstream of the scientific community. Tibor Ganti was one of those early pioneers, proposing a theoretical framework to understand the living principles in terms of chemical transformation cycles and their coupling. The turn of the century then brought with it a novel 'systems' paradigm, which shined light on all that previous work and carried many implications for the way we conceive of chemical and biological complexity today. In this article tribute is paid to some of those seminal contributions, highlighting the importance of adopting a systems view in present chemistry, particularly if plausible mechanisms of chemical evolution toward the first living entities want to be unraveled. We examine and put in perspective recent discoveries in the emerging subfield of 'prebiotic systems chemistry', reaching the conclusion that the functional coupling of protocellular subsystems (i.e., protometabolism, protogenome and membrane compartment) is the most challenging target to make qualitative advances in the problem of the origins of life. For the long-awaited goal of assembling an autonomous protocell from its most basic molecular building blocks, we further suggest that a systems integrative strategy should be considered from the earliest synthetic steps, already at the level of monomer precursors, opening the way to biogenesis.

Phthalocyanine-DNA origami complexes with enhanced stability and optical properties.

In this communication, electrostatically assembled phthalocyanine (Pc)-DNA origami (DO) complexes are formed and their optical properties are demonstrated. The formation of the complex prevents the Pc aggregation, thus yielding an enhanced optical response and photooxidative resilience towards aggregation in biologically relevant media. Simultaneously, the Pc protects the DO against enzymatic digestion. Both features solve previous drawbacks associated with phthalocyanine photosensitizers and DNA nanocarriers. The studied complexes may find use in technologies related to the photogeneration of singlet oxygen, e.g., photocatalysis, diagnositic arrays and photodynamic therapy.

Amphiphilic phthalocyanines in polymeric micelles: a supramolecular approach toward efficient third-generation photosensitizers.

In this paper we describe a straightforward supramolecular strategy to encapsulate silicon phthalocyanine (SiPc) photosensitizers (PS) in polymeric micelles made of poly(ε-caprolactone)-b-methoxypoly(ethylene glycol) (PCL-PEG) block copolymers. While PCL-PEG micelles are promising nanocarriers based on their biocompatibility and biodegradability, the design of our new PS favors their encapsulation. In particular, they combine two axial benzoyl substituents, each of them carrying either three hydrophilic methoxy(triethylenoxy) chains (1), three hydrophobic dodecyloxy chains (3), or both kinds of chains (2). The SiPc derivatives 1 and 2 are therefore amphiphilic, with the SiPc unit contributing to the hydrophobic core, while lipophilicity increases along the series, making it possible to correlate the loading efficacy in PCL-PEG micelles with the hydrophobic/hydrophilic balance of the PS structure. This has led to a new kind of third-generation nano-PS that efficiently photogenerates 1O2, while preliminary in vitro experiments demonstrate an excellent cellular uptake and a promising PDT activity.

Controlled integration of polymers into viral capsids.

In this paper, we describe the controlled incorporation of two synthetic polymers with different structures in the cowpea chlorotic mottle virus (CCMV) capsid. Poly(ethylene glycol) (PEG) chains have been attached to the amine groups of lysine residues on the outer surface of the viral capsid. The functionalization of CCMV with PEG chains provoked a slow but irreversible dissociation of the virus into PEG-coat protein (CP) subunits, likely due to steric interference between the protein-protein subunits as a result of the presence of the PEG chains. This thermodynamic instability, however, can be overcome if a second polymer, such as polystyrene sulfonate (PSS), is present within the capsid. After complete disassembly of the PEG-CCMV conjugates and removal of the viral RNA, incubation of the PEG-functionalized coat proteins with PSS resulted in the formation of much more robust PSS-CCMV-PEG capsids with a diameter of 18 nm (T = 1 capsids). These are the first virus-like particles bearing synthetic organic polymers both inside and outside the viral capsid, opening a new route to the synthesis of biohybrid nanostructured materials based on viruses.

Macrophage selective photodynamic therapy by meta-tetra(hydroxyphenyl)chlorin loaded polymeric micelles: A possible treatment for cardiovascular diseases.

Selective elimination of macrophages by photodynamic therapy (PDT) is a new and promising therapeutic modality for the reduction of atherosclerotic plaques. m-Tetra(hydroxyphenyl)chlorin (mTHPC, or Temoporfin) may be suitable as photosensitizer for this application, as it is currently used in the clinic for cancer PDT. In the present study, mTHPC was encapsulated in polymeric micelles based on benzyl-poly(ε-caprolactone)-b-methoxy poly(ethylene glycol) (Ben-PCL-mPEG) using a film hydration method, with loading capacity of 17%. Because of higher lipase activity in RAW264.7 macrophages than in C166 endothelial cells, the former cells degraded the polymers faster, resulting in faster photosensitizer release and higher in vitro photocytotoxicity of mTHPC-loaded micelles in those macrophages. However, we observed release of mTHPC from the micelles in 30min in blood plasma in vitro which explains the observed similar in vivo pharmacokinetics of the mTHPC micellar formulation and free mTHPC. Therefore, we could not translate the beneficial macrophage selectivity from in vitro to in vivo. Nevertheless, we observed accumulation of mTHPC in atherosclerotic lesions of mice aorta's which is probably the result of binding to lipoproteins upon release from the micelles. Therefore, future experiments will be dedicated to increase the stability and thus allow accumulation of intact mTHPC-loaded Ben-PCL-mPEG micelles to macrophages of atherosclerotic lesions.