Natural, biphasic calcium phosphate from fish bones for enamel remineralization and dentin tubules occlusion.

OBJECTIVES: A calcium phosphate extracted from fish bones (CaP-N) was evaluated for enamel remineralization and dentinal tubules occlusion. METHODS: CaP-N was characterized by assessing morphology by SEM, crystallinity by PXRD, and composition by ICP-OES. CaP-N morphology, crystallinity, ion release, and pH changes over time in neutral and acidic solutions were studied. CaP-N was then tested to assess remineralization and dentinal tubules occlusion on demineralized human enamel and dentin specimens (n = 6). Synthetic calcium phosphate in form of stoichiometric hydroxyapatite nanoparticles (CaP-S) and tap water were positive and negative controls, respectively. After treatment (brush every 12 h for 5d and storage in Dulbecco's modified PBS), specimens' morphology and surface composition were assessed (by SEM-EDS), while the viscoelastic behavior was evaluated with microindentation and DMA. RESULTS: CaP-N consisted of rounded microparticles (200 nm - 1 µm) composed of 33 wt% hydroxyapatite and 67 wt% ß-tricalcium phosphate. In acidic solution, CaP-N released calcium and phosphate ions thanks to the preferential ß-tricalcium phosphate phase dissolution. Enamel remineralization was induced by CaP-N comparably to CaP-S, while CaP-N exhibited a superior dentinal tubule occlusion than CaP-S, forming mineral plugs and depositing new nanoparticles onto demineralized collagen. This behavior was attributed to its bigger particle size and increased solubility. DMA depth profiling and SEM showed an excellent interaction between the newly formed mineralized structures and the pristine tissue, particularly at the exposed collagen fibrils. SIGNIFICANCE: CaP-N demonstrated very good remineralizing and occlusive activity in vitro, comparable to CaP-S, thus could be a promising circular economy alternative therapeutic agent for dentistry.

Lung-to-Heart Nano-in-Micro Peptide Promotes Cardiac Recovery in a Pig Model of Chronic Heart Failure.

BACKGROUND: The lack of disease-modifying drugs is one of the major unmet needs in patients with heart failure (HF). Peptides are highly selective molecules with the potential to act directly on cardiomyocytes. However, a strategy for effective delivery of therapeutics to the heart is lacking. OBJECTIVES: In this study, the authors sought to assess tolerability and efficacy of an inhalable lung-to-heart nano-in-micro technology (LungToHeartNIM) for cardiac-specific targeting of a mimetic peptide (MP), a first-in-class for modulating impaired L-type calcium channel (LTCC) trafficking, in a clinically relevant porcine model of HF. METHODS: Heart failure with reduced ejection fraction (HFrEF) was induced in Göttingen minipigs by means of tachypacing over 6 weeks. In a setting of overt HFrEF (left ventricular ejection fraction [LVEF] 30% ± 8%), animals were randomized and treatment was started after 4 weeks of tachypacing. HFrEF animals inhaled either a dry powder composed of mannitol-based microparticles embedding biocompatible MP-loaded calcium phosphate nanoparticles (dpCaP-MP) or the LungToHeartNIM only (dpCaP without MP). Efficacy was evaluated with the use of echocardiography, invasive hemodynamics, and biomarker assessment. RESULTS: DpCaP-MP inhalation restored systolic function, as shown by an absolute LVEF increase over the treatment period of 17% ± 6%, while reversing cardiac remodeling and reducing pulmonary congestion. The effect was recapitulated ex vivo in cardiac myofibrils from treated HF animals. The treatment was well tolerated, and no adverse events occurred. CONCLUSIONS: The overall tolerability of LungToHeartNIM along with the beneficial effects of the LTCC modulator point toward a game-changing treatment for HFrEF patients, also demonstrating the effective delivery of a therapeutic peptide to the diseased heart.

Inhalable Microparticles Embedding Biocompatible Magnetic Iron-Doped Hydroxyapatite Nanoparticles.

Recently, there has been increasing interest in developing biocompatible inhalable nanoparticle formulations, as they have enormous potential for treating and diagnosing lung disease. In this respect, here, we have studied superparamagnetic iron-doped calcium phosphate (in the form of hydroxyapatite) nanoparticles (FeCaP NPs) which were previously proved to be excellent materials for magnetic resonance imaging, drug delivery and hyperthermia-related applications. We have established that FeCaP NPs are not cytotoxic towards human lung alveolar epithelial type 1 (AT1) cells even at high doses, thus proving their safety for inhalation administration. Then, D-mannitol spray-dried microparticles embedding FeCaP NPs have been formulated, obtaining respirable dry powders. These microparticles were designed to achieve the best aerodynamic particle size distribution which is a critical condition for successful inhalation and deposition. The nanoparticle-in-microparticle approach resulted in the protection of FeCaP NPs, allowing their release upon microparticle dissolution, with dimensions and surface charge close to the original values. This work demonstrates the use of spray drying to provide an inhalable dry powder platform for the lung delivery of safe FeCaP NPs for magnetically driven applications.

Fluorescent Carbon Dots from Food Industry By-Products for Cell Imaging.

Herein, following a circular economy approach, we present the synthesis of luminescent carbon dots via the thermal treatment of chestnut and peanut shells, which are abundant carbon-rich food industry by-products. As-synthesized carbon dots have excellent water dispersibility thanks to their negative surface groups, good luminescence, and photo-stability. The excitation-emission behaviour as well as the surface functionalization of these carbon dots can be tuned by changing the carbon source (chestnuts or peanuts) and the dispersing medium (water or ammonium hydroxide solution). Preliminary in vitro biological data proved that the samples are not cytotoxic to fibroblasts and can act as luminescent probes for cellular imaging. In addition, these carbon dots have a pH-dependent luminescence and may, therefore, serve as cellular pH sensors. This work paves the way towards the development of more sustainable carbon dot production for biomedical applications.

An in situ study of thermal crystallization of amorphous calcium phosphates.

The heat-induced crystallization of amorphous calcium phosphate (ACP) is an intriguing process not yet well comprehended. This is because most of the works on this topic are based on ex situ studies where the materials are characterized after the heat and cooldown cycles, thus missing transient structural changes. Here, we used time-resolved energy dispersive X-ray diffraction and infrared spectroscopy to study, for the first time, the thermal crystallization of ACP in situ. The thermal crystallization of two kinds of citrate-stabilized carbonated ACP was studied, as they are promising materials for the preparation of advanced bioceramics. The behavior of these samples was compared to that of two citrate-free ACPs, either doped or non-doped with carbonate ions. Our results evinced that several phenomena occur during ACP thermal annealing. Before crystallization, all ACP samples undergo a decrease in the short-range order process, followed by several internal reorganizations. We have assessed that differently from carbonate-free ACP, carbonated ACPs with and without citrate directly crystallize into a biomimetic poorly crystalline carbonated hydroxyapatite. Citrate-stabilized ACPs in comparison to citrate-free ACPs have a faster hydroxyapatite formation kinetics, which is due to their higher specific surface area. This work reveals the necessity and the potentialities of using in situ techniques to effectively probe complex processes such as the heat-induced crystallization of ACPs.

Calcium Phosphates from Fishery Byproducts as a Booster of the Sun Protection Factor in Sunscreens.

Calcium phosphates (CaPs) have been recently proposed as a bio- and eco-compatible alternative to UV filters in sunscreens, which are in the spotlight for being associated with health risks for both people and the environment. Here, natural CaPs extracted from fish bones have been tested as a booster of the sun protection factor (SPF), that is, as material working in synergy with UV filters to increase sunscreen UV-shielding efficiency, in combination with three of the most used UV filters, namely, octocrylene (OCR), octinoxate, and padimate-O, at different concentrations (10.0 and 20.0 wt %). The material obtained by calcination at 800 °C (CaP-N) was also enriched with Zn (CaP-Zn) or Mn (CaP-Mn) in an attempt to increase its SPF-boosting abilities. CaP-N and CaP-Zn consisted of a biphasic mixture of hydroxyapatite and beta tricalcium phosphate, while CaP-Mn presented a small quantity of Mn oxides. CaP-N was the most effective at increasing the SPF of the final emulsions, doubling the SPF of the formulation containing 20.0 wt % of OCR from 40.6 to 80.8. The results show that these CaPs, produced according to a circular economy approach, can be used as effective SPF boosters to decrease the concentration of UV filters used in sunscreen, while retaining high SPF values.

Dental tissue remineralization by bioactive calcium phosphate nanoparticles formulations.

Recent health care products are based on formulations claimed to provide enamel remineralization and dentinal tubules occlusion through calcium-phosphate bioactive nanocompounds (ion-doped hydroxyapatite and precursor, amorphous calcium phosphate nanoparticles). This study aimed to characterize, test, and compare for the first time the structure and performance of a representative, market-available sample of remineralizing toothpastes and topical mousses. Formulations were characterized to determine their composition and investigate the presence of bioactive compounds and doping elements. A conventional fluoride-containing toothpaste was used as reference. The enamel remineralization and efficacy of dentinal tubules occlusion by tested formulations were investigated ex vivo on human hard tissues. All formulations containing Ca-P bioactive nanocompounds showed remineralizing ability by epitaxial growth of a layer showing the morphology and composition of human hydroxyapatite. Such layers also embedded nanosilica clusters. The presence of doping elements or casein phosphopeptide seemed essential to allow such performances, especially when hydroxyapatite and amorphous calcium phosphate compounds were doped with small amounts of CO32-, F-, Mg2+, and Sr2+. Topical mousse formulations showed a higher tubules occlusion capability than toothpastes, independently from their composition. Therefore, all tested formulations could be useful in restoring tooth structures in a biomimetic way, contrasting dental demineralization processes leading to caries.

Biocompatible antimicrobial colistin loaded calcium phosphate nanoparticles for the counteraction of biofilm formation in cystic fibrosis related infections.

The use of inhalable nanoparticles (NPs) for cystic fibrosis (CF) has been advocated as a promising tool to improve the efficacy of antimicrobials taking advantage of their ability to penetrate airway mucus and pathogen biofilm and to release the drug in or in proximity to the enclosed bacteria. Here, inhalable calcium phosphate (CaP) NPs were functionalized with colistin (Col) which is one of the most active antimicrobials against Gram-negative bacteria. The adsorption kinetic and isotherm of Col on CaP-NPs were investigated and fitted according to different mathematical models and revealed an electrostatic interaction between positively charged amine groups of Col and negatively charged surface of CaP-NPs. The maximum Col payload was of about 50 mg g-1 of CaP-NPs. After functionalization, despite an increase of size (213 vs 95 nm), in citrate solution, CaP-NPs maintained a dimension and surface charge considered suitable for crossing mucus barrier. CaP-NPs do not interact with mucin and are able to permeate a layer of artificial mucus. In vitro tests on pulmonary cells demonstrated that CaP-NPs are not cytotoxic up to a concentration of 125 µg mL-1. The antimicrobial and antibiofilm activity of Col loaded CaP-NPs tested on Pseudomonas aeruginosa RP73, a clinical strain isolated from a CF patient, was similar to that of free Col demonstrating that the therapeutic effect of Col adsorbed on CaP-NPs was retained. This work represents the first attempt to use CaP-NPs as delivery system for the CF treatment. The encouraging results open the way to further studies.

Amorphous calcium phosphate, the lack of order is an abundance of possibilities.

For almost three decades from its discovery, amorphous calcium phosphate (ACP) was not considered a suitable biomaterial due to its structural instability. Thanks to its unique properties in respect to crystalline calcium phosphate phases, nowadays ACP is used in promising devices for hard tissue regeneration. Here we have highlighted the features of ACP that were harnessed to create excellent biomaterials for dental remineralization, self-setting bone cements, drug delivery, and coatings of prostheses. Its current limitations as well as future perspectives of development were concisely described. Despite more research works are needed, we envisage that the future of ACP is bright.

Inhalable Microparticles Embedding Calcium Phosphate Nanoparticles for Heart Targeting: The Formulation Experimental Design.

Inhalation of Calcium Phosphate nanoparticles (CaPs) has recently unmasked the potential of this nanomedicine for a respiratory lung-to-heart drug delivery targeting the myocardial cells. In this work, we investigated the development of a novel highly respirable dry powder embedding crystalline CaPs. Mannitol was selected as water soluble matrix excipient for constructing respirable dry microparticles by spray drying technique. A Quality by Design approach was applied for understanding the effect of the feed composition and spraying feed rate on typical quality attributes of inhalation powders. The in vitro aerodynamic behaviour of powders was evaluated using a medium resistance device. The inner structure and morphology of generated microparticles were also studied. The 1:4 ratio of CaPs/mannitol led to the generation of hollow microparticles, with the best aerodynamic performance. After microparticle dissolution, the released nanoparticles kept their original size.

The Use of Calcium Phosphates in Cosmetics, State of the Art and Future Perspectives.

Calcium phosphates (CaPs) belong to a class of biomimetic materials widely employed for medical applications thanks to their excellent properties, such as biodegradability, biocompatibility and osteoinductivity. The recent trend in the cosmetics field of substituting potentially hazardous materials with natural, safe, and sustainable ingredients for the health of consumers and for the environment, as well as the progress in the materials science of academics and chemical industries, has opened new perspectives in the use of CaPs in this field. While several reviews have been focused on the applications of CaP-based materials in medicine, this is the first attempt to catalogue the properties and use of CaPs in cosmetics. In this review a brief introduction on the chemical and physical characteristics of the main CaP phases is given, followed by an up-to-date report of their use in cosmetics through a large literature survey of research papers and patents. The application of CaPs as agents in oral care, skin care, hair care, and odor control has been selected and extensively discussed, highlighting the correlation between the chemical, physical and toxicological properties of the materials with their final applications. Finally, perspectives on the main challenges that should be addressed by the scientific community and cosmetics companies to widen the application of CaPs in cosmetics are given.

Thermal crystallization of amorphous calcium phosphate combined with citrate and fluoride doping: a novel route to produce hydroxyapatite bioceramics.

Amorphous calcium phosphate (ACP) is a material of high interest for dentistry, orthopedics, and other biomedical sectors. Being intrinsically metastable, the process of transformation of ACP into a crystalline phase upon heating is of high relevance for the development of innovative bioceramics. Here we have first studied the thermal behavior of a citrate-stabilized ACP (Cit-ACP) also doped with fluoride ions (Cit-FACP) prepared at three different nominal Cit/Ca ratios (i.e. 4, 2, 1) by differential thermal analysis. Next, the physico-chemical features of the crystalline products as well as the in vitro cell response to the materials were investigated. A citrate and fluoride free ACP sample was also tested as the blank. We have found that the activation energy of crystallization of Cit-(F)ACP samples is lower in comparison to the blank ACP and this is influenced by the nominal Cit/Ca molar ratio. Interestingly, we have discovered that the thermal treatment of Cit-(F)ACP at 800 °C yields hydroxyapatite (HA) or fluorapatite (FHA) as the main products differently from blank ACP that, like most of the ACPs reported in the literature, yields ß-tricalcium phosphate. This was attributed to the Ca/P ratio of Cit-(F)ACP, which is similar to HA. A study of the crystalline products has revealed that all the (F)HA samples were non-cytotoxic, and retained carbonate ions in the crystal structure despite the heat treatment that should have induced decarbonation. The morphology of the products is influenced by the nominal Cit/Ca ratio and the presence of fluoride, ranging from spherical nanoparticles to micrometric hexagonal rods. Overall, our results prove that the thermal crystallization of Cit-(F)ACP is markedly different from classic ACP based materials and the thermal treatment of Cit-(F)ACP represents an attractive route for producing pure bioactive HA ceramics.

The effect of chemical structure of carboxylate molecules on hydroxyapatite nanoparticles. A structural and morphological study.

Being the most abundant non-macromolecular organic component of bone, the role of citrate (Cit) in hydroxyapatite (HA) crystallization is of high relevance. In this work we have investigated the influence of hydroxycitrate (CitOH) and glutarate (Glr) on HA crystallization in terms of particle growth, composition, and morphology in comparison to Cit. CitOH and Glr have been selected for this work because they share the same backbone structure of Cit but bear different functional groups in the central region. Our data has revealed that CitOH strongly inhibits HA crystallization more efficiently than Cit. CitOH-HA nanoparticles are composed of platy, elongated particles similar to those of Cit-HA but they are ca. twice smaller and have a lower crystal order. On the other hand, Glr does not inhibit HA crystallization as Cit, but leads to the formation of OCP platelets that convert with maturation time to HA nanorods with larger aspect ratio than Cit-HA. In comparison to Cit-HA samples, Glr-HA nanoparticles have bigger dimensions, and higher structural order. Overall, our data reveal that the central carboxyl group of Cit is involved in the selective binding with HA crystal surface and in regulating HA crystal growth. The results of this work highlight new possibilities to control the formation of HA for designing advanced bioactive materials and give new insights on the role of the structure of Cit in regulating the HA morphology.

Nanotechnological approach and bio-inspired materials to face degenerative diseases in aging.

The aging of the world population is increasingly claimed as an alarming situation, since an ever-raising number of persons in advanced age but still physically active is expected to suffer from invalidating and degenerative diseases. The impairment of the endogenous healing potential provoked by the aging requires the development of more effective and personalized therapies, based on new biomaterials and devices able to direct the cell fate to stimulate and sustain the regrowth of damaged or diseased tissues. To obtain satisfactory results, also in cases where the cell senescence, typical of the elderly, makes the regeneration process harder and longer, the new solutions have to possess excellent ability to mimic the physiological extracellular environment and thus exert biomimetic stimuli on stem cells. To this purpose, the "biomimetic concept" is today recognized as elective to fabricate bioactive and bioresorbable devices such as hybrid osteochondral scaffolds and bioactive bone cements closely resembling the natural hard tissues and with enhanced regenerative ability. The review will illustrate some recent results related to these new biomimetic materials developed for application in different districts of the musculoskeletal system, namely bony, osteochondral and periodontal regions, and the spine. Further, it will be shown how new bioactive and superparamagnetic calcium phosphate nanoparticles can give enhanced results in cardiac regeneration and cancer therapy. Since tissue regeneration will be a major demand in the incoming decades, the high potential of biomimetic materials and devices is promising to significantly increase the healing rate and improve the clinical outcomes even in aged patients.

Characterization of a Toothpaste Containing Bioactive Hydroxyapatites and In Vitro Evaluation of Its Efficacy to Remineralize Enamel and to Occlude Dentinal Tubules.

Demineralization of dental hard tissues is a well-known health issue and the primary mechanism responsible for caries and dentinal hypersensitivity. Remineralizing toothpastes are nowadays available to improve conventional oral care formulations regarding the prevention and repair of demineralization. In this paper, we analyzed the chemical-physical features of a commercial toothpaste (Biosmalto Caries Abrasion and Erosion, Curasept S.p.A., Saronno, Italy), with particular attention paid to the water-insoluble fraction which contains the remineralizing bioactive ingredients. Moreover, the efficacy of the toothpaste to induce enamel remineralization and to occlude dentinal tubules has been qualitatively and semiquantitatively tested in vitro on human dental tissues using scanning electron microscopy and X-ray microanalysis. Our results demonstrated that the water-insoluble fraction contained silica as well as chitosan and poorly crystalline biomimetic hydroxyapatite doped with carbonate, magnesium, strontium, and fluoride ions. The formulation showed excellent ability to restore demineralized enamel into its native structure by epitaxial deposition of a new crystalline phase in continuity with the native one. It was also able to occlude the dentinal tubules exposed completely by acid-etching. Overall, this study demonstrated that the tested toothpaste contained a biomimetic ionic-substituted hydroxyapatite-based active principle and that, within the in vitro conditions analyzed in this study, it was effective in dental hard tissue remineralization.

Mussel Shell-Derived Macroporous 3D Scaffold: Characterization and Optimization Study of a Bioceramic from the Circular Economy.

Fish industry by-products constitute an interesting platform for the extraction and recovery of valuable compounds in a circular economy approach. Among them, mussel shells could provide a calcium-rich source for the synthesis of hydroxyapatite (HA) bioceramics. In this work, HA nanoparticles have been successfully synthesized starting from mussel shells (Mytilus edulis) with a two steps process based on thermal treatment to convert CaCO3 in CaO and subsequent wet precipitation with a phosphorus source. Several parameters were studied, such as the temperature and gaseous atmosphere of the thermal treatment as well as the use of two different phosphorus-containing reagents in the wet precipitation. Data have revealed that the characteristics of the powders can be tailored, changing the conditions of the process. In particular, the use of (NH4)2HPO4 as the phosphorus source led to HA nanoparticles with a high crystallinity degree, while smaller nanoparticles with a higher surface area were obtained when H3PO4 was employed. Further, a selected HA sample was synthesized at the pilot scale; then, it was employed to fabricate porous 3D scaffolds using the direct foaming method. A highly porous scaffold with open and interconnected porosity associated with good mechanical properties (i.e., porosity in the range 87-89%, pore size in the range 50-300 µm, and a compressive strength σ = 0.51 ± 0.14 MPa) suitable for bone replacement was achieved. These results suggest that mussel shell by-products are effectively usable for the development of compounds of high added value in the biomedical field.

Preclinical evaluation of platinum-loaded hydroxyapatite nanoparticles in an embryonic zebrafish xenograft model.

Hydroxyapatite (HA) nanoparticles are commonly used as building blocks in the design of bone-substituting biomaterials. Recently, these nanoparticles have been considered for the treatment of metastasis disease, since their pH-dependent dissolution behavior allows for precise tuning of release kinetics of loaded cargo. Herein we show that the capacity of drug-loaded nanoparticles stabilized with citrate ions reduce cancer cell survival in an embryonic zebrafish xenograft model. In particular, in vitro studies demonstrate that PtPP-loaded HA nanoparticles exhibit anti-proliferative activity against breast cancer cells at reduced pH. In vivo studies using an embryonic zebrafish xenograft model reveal that PtPP co-delivered with human breast cancer cells strongly reduce cancer cell survival. Similarly, co-injection of breast cancer cells with citrate-functionalized and PtPP-loaded HA nanoparticles into zebrafish significantly reduces survival of cancer cells due to release of chemotherapeutically active kiteplatin species. These results demonstrate the preclinical efficacy of drug-loaded nanoparticles against human breast cancer cells in a xenogenic embryonic in vivo model.

Fluoride-doped amorphous calcium phosphate nanoparticles as a promising biomimetic material for dental remineralization.

Demineralization of dental hard tissue is a widespread problem and the main responsible for dental caries and dentin hypersensitivity. The most promising strategies to induce the precipitation of new mineral phase are the application of materials releasing gradually Ca2+ and PO43- ions or mimicking the mineral phase of the host tissue. However, the design of formulations covering both processes is so far a challenge in preventive dentistry. In this work, we have synthesized innovative biomimetic amorphous calcium phosphate (ACP), which has been, for the first time, doped with fluoride ions (FACP) to obtain materials with enhanced anti-caries and remineralizing properties. Significantly, the doping with fluoride (F) did not vary the physico-chemical features of ACP but resulted in a faster conversion to the crystalline apatite phase in water, as observed by in-situ time-dependent Raman experiments. The efficacy of the as synthesized ACP and FACP samples to occlude dentinal tubules and induce enamel remineralization has been tested in vitro in human molar teeth. The samples showed good ability to partially occlude the tubules of acid-etched dentin and to restore demineralized enamel into its native structure. Results demonstrate that ACP and FACP are promising biomimetic materials in preventive dentistry to hinder demineralization of dental hard tissues.

Calcium phosphate-based nanosystems for advanced targeted nanomedicine.

Synthetic calcium phosphates (CaPs) are the most widely accepted bioceramics for the repair and reconstruction of bone tissue defects. The recent advancements in materials science have prompted a rapid progress in the preparation of CaPs with nanometric dimensions, tailored surface characteristics, and colloidal stability opening new perspectives in their use for applications not strictly related to bone. In particular, the employment of CaPs nanoparticles as carriers of therapeutic and imaging agents has recently raised great interest in nanomedicine. CaPs nanoparticles, as well as other kinds of nanoparticles, can be engineered to specifically target the site of the disease (cells or organs), thus minimizing their dispersion in the body and undesired organism-nanoparticles interactions. The most promising and efficient approach to improve their specificity is the 'active targeting', where nanoparticles are conjugated with a targeting moiety able to recognize and bind with high efficacy and selectivity to receptors that are highly expressed only in the therapeutic site. The aim of this review is to give an overview on advanced targeted nanomedicine with a focus on the most recent reports on CaP nanoparticles-based systems, specifically designed for the active targeting. The distinctive characteristics of CaP nanoparticles with respect to the other kinds of nanomaterials used in nanomedicine are also discussed.

Plugging a Bipyridinium Axle into Multichromophoric Calix[6]arene Wheels Bearing Naphthyl Units at Different Rims.

Tris-(N-phenylureido)-calix[6]arene derivatives are heteroditopic non-symmetric molecular hosts that can form pseudorotaxane complexes with 4,4'-bipyridinium-type guests. Owing to the unique structural features and recognition properties of the calix[6]arene wheel, these systems are of interest for the design and synthesis of novel molecular devices and machines. We envisaged that the incorporation of photoactive units in the calixarene skeleton could lead to the development of systems the working modes of which can be governed and monitored by means of light-activated processes. Here, we report on the synthesis, structural characterization, and spectroscopic, photophysical, and electrochemical investigation of two calix[6]arene wheels decorated with three naphthyl groups anchored to either the upper or lower rim of the phenylureido calixarene platform. We found that the naphthyl units interact mutually and with the calixarene skeleton in a different fashion in the two compounds, which thus exhibit a markedly distinct photophysical behavior. For both hosts, the inclusion of a 4,4'-bipyridinium guest activates energy- and/or electron-transfer processes that lead to non-trivial luminescence changes.