Special Issue "Materials for Photobiology".

Photobiology is a challenging research area that aims to explore the interactions between light and living organisms and their biological consequences, with applications in the fields of photomedicine, photo(nano)technology, photosynthesis, and photosensory biology [...].

A Kinetic Investigation of the Supramolecular Chiral Self-Assembling Process of Cationic Organometallic (2,2':6',2″-terpyridine)methylplatinum(II) Complexes with Poly(L-glutamic Acid).

The cationic platinum(II) organometallic complex [Pt(terpy)Me]+ (terpy = 2,2':6',2″-terpyridine) at mild acidic pH interacts with poly(L-glutamic acid) (L-PGA) in its α-helix conformation, affording chiral supramolecular adducts. Their kinetics of formation have been investigated in detail as a function of the concentrations of both reagents and changing pH, ionic strength, the length of the polymeric scaffold and temperature. After a very fast early stage, the kinetic traces have been analyzed as three consecutive steps, suggesting a mechanism based on the electrostatic fast formation of a not-organized aggregate that subsequently evolves through different rearrangements to form the eventual supramolecular adduct. A model for this species has been proposed based on (i) the attractive electrostatic interaction of the cationic platinum(II) complexes and the polyelectrolyte and (ii) the π-stacking interactions acting among the [Pt(terpy)Me]+ units.

Antimicrobial and Antibiofilm Photodynamic Action of Photosensitizing Nanoassemblies Based on Sulfobutylether-ß-Cyclodextrin.

Developing new broad-spectrum antimicrobial strategies, as alternatives to antibiotics and being able to efficiently inactivate pathogens without inducing resistance, is one of the main objectives in public health. Antimicrobial photodynamic therapy (aPDT), based on the light-induced production of reactive oxygen species from photosensitizers (PS), is attracting growing interest in the context of infection treatment, also including biofilm destruction. Due to the limited photostability of free PS, delivery systems are increasingly needed in order to decrease PS photodegradation, thus improving the therapeutic efficacy, as well as to reduce collateral effects on unaffected tissues. In this study, we propose a photosensitizing nanosystem based on the cationic porphyrin 5,10,15,20-tetrakis (N-methyl- 4-pyridyl)-21H,23H-porphyrin (TMPyP), complexed with the commerical sulfobutylether-beta-cyclodextrin (CAPTISOL®), at a 1:50 molar ratio (CAPTISOL®/TMPyP)50_1. Nanoassemblies based on (CAPTISOL®/TMPyP)50_1 with photodynamic features exhibited photo-antimicrobial activity against Gram-negative and Gram-positive bacteria. Moreover, results from P. aeruginosa reveal that CAPTISOL® alone inhibits pyocyanin (PYO) production, also affecting bacterial biofilm formation. Finally, we obtained a synergistic effect of inhibition and destruction of P. aeruginosa biofilm by using the combination of CAPTISOL® and TMPyP.

Amphiphilic Cyclodextrin Nanoparticles as Delivery System for Idebenone: A Preformulation Study.

Idebenone (IDE), a synthetic short-chain analogue of coenzyme Q10, is a potent antioxidant able to prevent lipid peroxidation and stimulate nerve growth factor. Due to these properties, IDE could potentially be active towards cerebral disorders, but its poor water solubility limits its clinical application. Octanoyl-ß-cyclodextrin is an amphiphilic cyclodextrin (ACyD8) bearing, on average, ten octanoyl substituents able to self-assemble in aqueous solutions, forming various typologies of supramolecular nanoassemblies. Here, we developed nanoparticles based on ACyD8 (ACyD8-NPs) for the potential intranasal administration of IDE to treat neurological disorders, such as Alzheimer's Disease. Nanoparticles were prepared using the nanoprecipitation method and were characterized for their size, zeta potential and morphology. STEM images showed spherical particles, with smooth surfaces and sizes of about 100 nm, suitable for the proposed therapeutical aim. The ACyD8-NPs effectively loaded IDE, showing a high encapsulation efficiency and drug loading percentage. To evaluate the host/guest interaction, UV-vis titration, mono- and two-dimensional NMR analyses, and molecular modeling studies were performed. IDE showed a high affinity for the ACyD8 cavity, forming a 1:1 inclusion complex with a high association constant. A biphasic and sustained release of IDE was observed from the ACyD8-NPs, and, after a burst effect of about 40%, the release was prolonged over 10 days. In vitro studies confirmed the lack of toxicity of the IDE/ACyD8-NPs on neuronal SH-SY5Y cells, and they demonstrated their antioxidant effect upon H2O2 exposure, as a general source of ROS.

Intracellular Fate and Impact on Gene Expression of Doxorubicin/Cyclodextrin-Graphene Nanomaterials at Sub-Toxic Concentration.

The graphene road in nanomedicine still seems very long and winding because the current knowledge about graphene/cell interactions and the safety issues are not yet sufficiently clarified. Specifically, the impact of graphene exposure on gene expression is a largely unexplored concern. Herein, we investigated the intracellular fate of graphene (G) decorated with cyclodextrins (CD) and loaded with doxorubicin (DOX) and the modulation of genes involved in cancer-associated canonical pathways. Intracellular fate of GCD@DOX, tracked by FLIM, Raman mapping and fluorescence microscopy, evidenced the efficient cellular uptake of GCD@DOX and the presence of DOX in the nucleus, without graphene carrier. The NanoString nCounter™ platform provided evidence for 34 (out of 700) differentially expressed cancer-related genes in HEp-2 cells treated with GCD@DOX (25 µg/mL) compared with untreated cells. Cells treated with GCD alone (25 µg/mL) showed modification for 16 genes. Overall, 14 common genes were differentially expressed in both GCD and GCD@DOX treated cells and 4 of these genes with an opposite trend. The modification of cancer related genes also at sub-cytotoxic G concentration should be taken in consideration for the rational design of safe and effective G-based drug/gene delivery systems. The reliable advantages provided by NanoString® technology, such as sensibility and the direct RNA measurements, could be the cornerstone in this field.

Folate-Decorated Amphiphilic Cyclodextrins as Cell-Targeted Nanophototherapeutics.

Nowadays, active targeting of nanotherapeutics is a challenging issue. Here, we propose a rational design of a ternary nanoassembly (SAP) composed of nonionic amphiphilic ß-cyclodextrins (amphiphilic CD) incorporating pheophorbide (Pheo) as a phototherapeutic and an adamantanyl-folic acid conjugate (Ada-FA) to target tumor cells overexpressing α-folate receptor (FR-α(+)). Dynamic light scattering and ζ-potential pointed out the presence of nanoassemblies bearing a negative surface charge (ζ = -51 mV). Morphology of SAP was investigated by atomic force microscopy and microphotoluminescence, indicating the presence of highly emissive near-spherical assemblies of about 280 nm in size. Complementary spectroscopic techniques such as ROESY-NMR, UV/vis and steady-state fluorescence revealed that the folic acid protrudes out of amphiphilic CD rims, prone for recognition with FR-α. Pheo was strongly loaded in the nanoassembly mostly in monomeric form, thus generating singlet oxygen (1O2) and consequentely showing phototherapeutic action. SAP remained stable until 2 weeks in aqueous solutions. Stability studies in biologically relevant media pointed out the ability of SAP to interact with serum proteins by means of the oligoethylenglycole fringe, without destabilization. Release experiments demonstrated the sustained release of Pheo from SAP in environments mimiking physiological conditions (∼20% within 1 week), plausibly suggesting low Pheo leaking and high integrity of the assembly within 24 h, time spent on average to reach the target sites. Cellular uptake of SAP was confirmed by confocal microscopy, pointing out that SAP was internalized into the tumoral cells expressing FR-α more efficiently than SP. SAP showed improved phototoxicity in human breast MCF-7 cancer cells FR-α(+) (IC50 = 270 nM) with respect to human prostate carcinoma PC3 cells (IC50 = 700 nM) that express a low level of that receptor (FR-α(-)). Finally, an improved phototoxicity in FR-α(+) MCF-7 cells (IC50 = 270 nM) was assessed after treatment with SAP vs SP (IC50 = 600 nM) which was designed without Ada-FA as a targeting unit.

Supramolecular Adducts of Anionic Porphyrins and a Biocompatible Polyamine: Effect of Photodamage-on Human Red Blood Cells.

Supramolecular adducts obtained by interaction between the anionic porphyrin meso-tetrakis(4-carboxyphenyl)porphyrin (TPPC) or its zinc(II) derivative (ZnTPPC) with a biocompatible amino-terminated polypropylene or poly(ethylene oxide)s (Jeffamines) has been investigated. The interaction with the polymer allows the stabilization of the porphyrins in their monomeric form under physiological conditions. The photodynamic properties of the supramolecular adducts were explored by typical 1O2 indirect detection. Their photodynamic action were evaluated in vitro using human red blood cells (HRBCs) under different experimental conditions. The morphology of erythrocytes was investigated by optical microscopy after incubation with porphyrin compounds and light irradiation. The images show loss of their normal biconcave profile and an incoming spiny configuration with blebs evident on their surfaces.

Cellular Signaling Pathways Activated by Functional Graphene Nanomaterials.

The paper reviews the network of cellular signaling pathways activated by Functional Graphene Nanomaterials (FGN) designed as a platform for multi-targeted therapy or scaffold in tissue engineering. Cells communicate with each other through a molecular device called signalosome. It is a transient co-cluster of signal transducers and transmembrane receptors activated following the binding of transmembrane receptors to extracellular signals. Signalosomes are thus efficient and sensitive signal-responding devices that amplify incoming signals and convert them into robust responses that can be relayed from the plasma membrane to the nucleus or other target sites within the cell. The review describes the state-of-the-art biomedical applications of FGN focusing the attention on the cell/FGN interactions and signalosome activation.

Poly(carboxylic acid)-Cyclodextrin/Anionic Porphyrin Finished Fabrics as Photosensitizer Releasers for Antimicrobial Photodynamic Therapy.

In the development of new antibacterial therapeutic approaches to fight multidrug-resistant bacteria, antimicrobial photodynamic therapy (aPDT) represents a well-known alternative to treat local infections caused by different microorganisms. Here we present a polypropylene (PP) fabric finished with citrate-hydroxypropyl-ßCD polymer (PP-CD) entrapping the tetra-anionic 5,10,15,20-tetrakis(4-sulfonatophenyl)-21H,23H-porphine (TPPS) as photosensitizer-eluting scaffold (PP-CD/TPPS) for aPDT. The concept is based on host-guest complexation of porphyrin in the cavities of CDs immobilized on the PP fibers, followed by its sustained and controlled delivery in release medium and simultaneous photoinactivation of microorganisms. Morphology of fabric was characterized by optical (OM) and scanning electron microscopies (SEM). Optical properties were investigated by UV-vis absorption, steady- and time-resolved fluorescence emission spectroscopy. X-ray photoelectron spectroscopy (XPS) and FT-IR revealed the surface chemical composition and the distribution map of the molecular components on the fabric, respectively. Direct 1O2 determination allowed to assess the potential photodynamic activity of the fabric. Release kinetics of TPPS in physiological conditions pointed out the role of the CD cavity to control the TPPS elution. Photoantimicrobial activity of the porphyrin-loaded textile was investigated against both Gram-positive Staphylococcus aureus ATCC 29213 (S. aureus) and Gram-negative Pseudomonas aeruginosa ATCC 27853 (P. aeruginosa). Optical microscopy coupled with UV-vis extinction and fluorescence spectra aim to ascertain the uptake of TPPS to S. aureus bacterial cells. Finally, PP-CD/TPPS fabric-treated S. aureus cells were photokilled of 99.98%. Moreover, low adhesion of S. aureus cells on textile was established. Conversely, no photodamage of fabric-treated P. aeruginosa cells was observed, together with their satisfying adhesion.

Aggregation behavior of amphiphilic cyclodextrins in a nonpolar solvent: evidence of large-scale structures by atomistic molecular dynamics simulations and solution studies.

Chemically modified cyclodextrins carrying both hydrophobic and hydrophilic substituents may form supramolecular aggregates or nanostructures of great interest. These systems have been usually investigated and characterized in water for their potential use as nanocarriers for drug delivery, but they can also aggregate in apolar solvents, as shown in the present paper through atomistic molecular dynamics simulations and dynamic light scattering measurements. The simulations, carried out with a large number of molecules in vacuo adopting an unbiased bottom-up approach, suggest the formation of bidimensional structures with characteristic length scales of the order of 10 nm, although some of these sizes are possibly affected by the assumed periodicity of the simulation cell, in particular at longer lengths. In any case, these nanostructures are stable at least from the kinetic viewpoint for relatively long times thanks to the large number of intermolecular interactions of dipolar and dispersive nature. The dynamic light scattering experiments indicate the presence of aggregates with a hydrodynamic radius of the order of 80 nm and a relatively modest polydispersity, even though smaller nanometer-sized aggregates cannot be fully ruled out. Taken together, these simulation and experimental results indicate that amphiphilically modified cyclodextrins do also form large-scale nanoaggregates even in apolar solvents.

Nanoassemblies Based on Supramolecular Complexes of Nonionic Amphiphilic Cyclodextrin and Sorafenib as Effective Weapons to Kill Human HCC Cells.

Sorafenib (Sor), an effective chemiotherapeutic drug utilized against hepatocellular carcinoma (HCC), robustly interacts with nonionic amphiphilic cyclodextrin (aCD, SC6OH), forming, in aqueous solution, supramolecular complexes that behave as building blocks of highly water-dispersible colloidal nanoassemblies. SC6OH/Sor complex has been characterized by complementary spectroscopic techniques, such as UV-vis, steady-state fluorescence and anisotropy, resonance light scattering and (1)H NMR. The spectroscopic evidences and experiments carried out in the presence of an adamantane derivative, which competes with drug for CD cavity, agree with the entrapment of Sor in aCD, pointing out the role of the aCD cavity in the interaction between drug and amphiphile. Nanoassemblies based on SC6OH/Sor display size of ∼200 nm, negative zeta-potential (ζ = -11 mV), and both maximum loading capacity (LC ∼ 17%) and entrapment efficiency (EE ∼ 100%). Kinetic release profiles show a slower release of Sor from nanoassemblies with respect to the free drug. SC6OH/Sor nanoassemblies have very low hemolytic activity and high efficiency in vitro in decreasing cell growth and viability of HCC cell lines, such as HepG2, Hep3B, and PLC/PRF/5, opening promising chances to their in vivo applications.

Aggregation behaviour of amphiphilic cyclodextrins: the nucleation stage by atomistic molecular dynamics simulations.

Amphiphilically modified cyclodextrins may form various supramolecular aggregates. Here we report a theoretical study of the aggregation of a few amphiphilic cyclodextrins carrying hydrophobic thioalkyl groups and hydrophilic ethylene glycol moieties at opposite rims, focusing on the initial nucleation stage in an apolar solvent and in water. The study is based on atomistic molecular dynamics methods with a "bottom up" approach that can provide important information about the initial aggregates of few molecules. The focus is on the interaction pattern of amphiphilic cyclodextrin (aCD), which may interact by mutual inclusion of the substituent groups in the hydrophobic cavity of neighbouring molecules or by dispersion interactions at their lateral surface. We suggest that these aggregates can also form the nucleation stage of larger systems as well as the building blocks of micelles, vesicle, membranes, or generally nanoparticles thus opening new perspectives in the design of aggregates correlating their structures with the pharmaceutical properties.

RGD-tagging of star-shaped PLA-PEG micellar nanoassemblies enhances doxorubicin efficacy against osteosarcoma.

We developed cyclic RGD-tagged polymeric micellar nanoassemblies for sustained delivery of Doxorubicin (Dox) endowed with significant cytotoxic effect against MG63, SAOS-2, and U2-OS osteosarcoma cells without compromising the viability of healthy osteoblasts (hFOBs). Targeted polymeric micellar nanoassemblies (RGD-NanoStar@Dox) enabled Dox to reach the nucleus of MG63, SAOS-2, and U2-OS cells causing the same cytotoxic effect as free Dox, unlike untargeted micellar nanoassemblies (NanoStar@Dox) which failed to reach the nucleus and resulted ineffective, demonstrating the crucial role of cyclic RGD peptide in driving cellular uptake and accumulation mechanisms in osteosarcoma cells. Micellar nanoassemblies were obtained by nanoformulation of three-armed star PLA-PEG copolymers properly synthetized with and without decoration with the cyclic-RGDyK peptide (Arg-Gly-Asp-D-Tyr-Lys). The optimal RGD-NanoStar@Dox nanoformulation obtained by nanoprecipitation method (8 % drug loading; 35 % encapsulation efficiency) provided a prolonged and sustained drug release with a rate significantly lower than the free drug under the same experimental conditions. Moreover, the nanosystem preserved Dox from the natural degradation occurring under physiological conditions (i.e., dimerization and consequent precipitation) serving as a slow-release "drug reservoir" ensuring an extended biological activity over the time.

Nanostructures of cationic amphiphilic cyclodextrin complexes with DNA.

Complexes of cationic amphiphilic cyclodextrins heptakis[2-(ω-amino-oligo(ethylene glycol))-6-deoxy-6-hexadecylthio]-ß-cyclodextrin and heptakis[2-(ω-amino-oligo(ethylene glycol))-6-deoxy-6-dodecylthio]-ß-cyclodextrin with DNA were examined by small-angle X-ray scattering and dynamic as well as electrophoretic light scattering. The first cyclodextrin forms bilayer vesicles in water, which, in the presence of calf thymus DNA, transform to a multilamellar complex. In this complex, the DNA lies between the two polar layers of the cyclodextrin's protonated amino groups in alternation with the lipidic bilayers. The cyclodextrin with shorter lipid chains, in contrast, forms micelles in water, and electrostatic clustering of these about DNA does not affect their intrinsic structure. These results are relevant to the potential of such cyclodextrins in therapeutic gene delivery, showing that their self-assembly modes in isolation influence their complex formation with DNA and possibly their efficiency in promoting cell transfection.

Supramolecular assemblies based on complexes of nonionic amphiphilic cyclodextrins and a meso-tetra(4-sulfonatophenyl)porphine tributyltin(IV) derivative: potential nanotherapeutics against melanoma.

Amphiphilic cyclodextrin (ACyD) provides water-soluble and adaptable nanovectors by modulating the balance between the hydrophobic and hydrophilic chains at both CyD sides. This work aimed to design nanoassemblies based on nonionic and hydrophilic ACyD (SC6OH) for the delivery of a poor-water-soluble organotin(IV)-porphyrin derivative [(Bu3Sn)4TPPS] to melanoma cancer cells. To characterize the porphyrin derivatives under simulated physiological conditions, a speciation was performed using complementary techniques. In aqueous solution (≤ 20 µM), (Bu3Sn)4TPPS primarily exists as a monomer (2 in Figure 1), as suggested by the low static anisotropy (ρ ≈ 0.02) with a negligible formation of porphyrin supramolecular aggregates. MALDI-TOF spectra indicate the presence of moieties (i.e., [(Bu3Sn)3TPPS](-)) that are derivatives of the monomeric species. Spectrofluorimetry coupled with potentiometric measurements primarily assesses the presence of the hydrolytic [(Bu3Sn)4TPPS (OH)4](4-) species under physiological conditions. Nanoassemblies of (Bu3Sn)4TPPS/SC6OH were prepared by dispersion of organic films in PBS at pH 7.4 and were investigated using a combination of spectroscopic and morphological techniques. The UV-vis and emission fluorescence spectra of the (Bu3Sn)4TPPS/SC6OH reveal shifts in the peculiar bands of the organotin(IV)-porphyrin derivative due to its interaction with the ACyD supramolecular assemblies in aqueous solution. The mean size was within the range of 100-120 nm. The ξ-potential was negative (-16 mV) for the (Bu3Sn)4TPPS/SC6OH nanoassemblies, with an entrapment efficiency of approximately 67%. The intracellular delivery, cytotoxicity, nuclear morphology and cell growth kinetics were evaluated via fluorescence microscopy on A375 human melanoma cells. The delivery of (Bu3Sn)4TPPS by ACyD with respect to free (Bu3Sn)4TPPS increases the internalization efficiency and cytotoxicity to induce apoptotic cell death and, at lower concentrations, changes the cellular morphology and prevents cell proliferation.

Aldol-type compounds from water-soluble indole-3,4-diones: synthesis, kinetics, and antiviral properties.

A straightforward transformation of indole-3,4-diones is reported. The reaction feasibility is evidenced by kinetic studies on a model substrate, revealing a double phase process with a first faster pseudo-first-order step (i.e., deprotonation of the dione and self-nucleophilic attack of the anion) and a subsequent slower dehydration of the intermediate. The overall process is faster at pH higher than the pK value of the investigated substrate. The biological relevance of new compounds has been assessed in vitro against herpes simplex virus type-1 (HSV-1), showing a more promising biological profile with respect to their precursors.

Harnessing the power of PLA-PEG nanoparticles for Linezolid delivery against methicillin-resistant Staphylococcus aureus.

This study deals with the development of novel poly(lactic acid)-poly(ethylene glycol) nanoparticles (PLA-PEG NPs) for the efficient and prolonged delivery of Linezolid (LNZ), a synthetic antibacterial agent used against methicillin-resistant Staphylococcus aureus (MRSA). A two-step synthetic strategy based on carbodiimide coupling and copper-catalyzed azide-alkyne cycloaddition was first exploited for the conjugation of PLA with PEG. The encapsulation of LNZ into medium-molecular-weight PLA-PEG NPs was carried out by different methods including nanoprecipitation and dialysis. The optimal PLA-PEG@LNZ nanoformulation resulted in 3.5% LNZ payload (15% encapsulation efficiency, with a 10:3 polymer to drug mass ratio) and sustained release kinetics with 65% of entrapped antibiotic released within 80 h. Moreover, the zeta potential values (from -31 to -39 mV) indicated a good stability without agglomeration even after freeze-drying and lyophilization. The PLA-PEG@LNZ NPs exerted antimicrobial activity against a panel of Gram-positive bacteria responsible for human infections, such as Staphylococcus aureus including MRSA, Staphylococcus epidermidis, Staphylococcus lugdunensis and vancomycin-resistant Enterococcus faecium (VREfm). Moreover, PLA-PEG@LNZ NPs showed inhibitory activity on both planktonic growth and preformed biofilm of MRSA. The antibacterial activity of LNZ incorporated in polymeric NPs was well preserved and the nanosystem served as an antibiotic enhancer with a potential role in MRSA-associated infections management.

Thermodynamic and voltammetric study on carnosine and ferrocenyl-carnosine.

A potentiometric study on the interactions of L-carnosine (CAR) (2-[(3-aminopropanoyl)amino]-3-(1H-imidazol-5-yl)propanoic acid) with two toxic metal cations, Hg2+ and Cd2+, is reported here. The elucidation of the metal (M2+)-CAR interactions in aqueous solution highlighted the speciation model for each system, the dependence of the formation constants of the complex species on ionic strength (0.15 ≤ I/mol L-1 ≤ 1) and temperature (288.15 ≤ T/K ≤ 310.15) and changes in enthalpy and entropy. The sequestering ability of CAR towards the two metal ions was quantified and compared with that with Pb2+, previously determined. Considering the complexing ability of CAR and its unclear electrochemical properties, a more electroactive derivative, the ferrocenyl-carnosine (FcCAR), was synthesized and its complexing ability was evaluated by UV-vis spectroscopy. FcCAR electrochemical properties were investigated by Cyclic Voltammetry (CV) and Differential Pulse Voltammetry (DPV) on Screen-Printed Electrodes (SPEs), to evaluate its sensing properties. Electrochemical responses in the presence of Hg2+ and Pb2+ have been shown to be promising for the electrochemical detection of these metal cations in aqueous environment.

Curcumin I-SMA nanomicelles as promising therapeutic tool to tackle bacterial infections.

Renewed interest towards natural substances has been pushed by the widespread diffusion of antibiotic resistance. Curcumin I is the most active and effective constituent of curcuminoids extracted from Curcuma longa and, among other beneficial effects, attracted attention for its antimicrobial potential. Since the poor pharmacokinetic profile hinders its efficient utilization, in the present paper, we report encapsulation of curcumin I in poly(styrene-co-maleic acid) (SMA-CUR) providing a nanomicellar system with improved aqueous solubility and bioavailability. SMA-CUR was characterized by means of size, zeta potential, polydispersity index, atomic force microscopy (AFM), drug release studies, spectroscopic properties and stability. SMA-CUR nanoformulation displayed exciting antimicrobial properties compared to free curcumin I towards Gram-positive and Gram-negative clinical isolates.

Supramolecular assemblies based on polymeric cyclodextrin nanosponges and a cationic porphyrin with antimicrobial photodynamic therapy action.

Within of the increasing requirement of alternative approaches to fight emerging infections, nano-photosensitisers (nanoPS) are currently designed with the aim to optimize the antimicrobial photodynamic (aPDT) efficacy. The utilize of less expensive nanocarriers prepared by simple and eco-friendly methodologies and commercial photosensitisers are highly desiderable. In this direction, here we propose a novel nanoassembly composed of water soluble anionic polyester ß-CD nanosponges (ß-CD-PYRO hereafter named ßNS) and the cationic 5,10,15,20-tetrakis(1-methylpyridinium-4- yl)porphine (TMPyP). Nanoassemblies were prepared in ultrapure water by mixing PS and ßNS, by exploiting their mutual electrostatic interaction, and characterized by various spectroscopic techniques such as UV/Vis, Steady-State and Time Resolved Fluorescence, Dynamic Light Scattering and ζ-potential. NanoPS produce appreciable amount of single oxygen similar to free porphyrin and a prolonged stability after 6 days of incubations in physiological conditions and following photoirradiation. Antimicrobial photodynamic action against fatal hospital-acquired infections such as P. aeruginosa and S. aureus was investigated by pointing out the ability of cationic porphyrin loaded- CD nanosponges to photo-kill bacterial cells at prolonged time of incubation and following irradiation (MBC99 = 3.75 µM, light dose = 54.82 J/cm2).