Synthesis and Intramolecular Energy- and Electron-Transfer of 3D-Conformeric Tris(fluorenyl-[60]fullerenylfluorene) Derivatives.

New 3D conformers were synthesized to show a nanomolecular configuration with geometrically branched 2-diphenylaminofluorene (DPAF-C2M) chromophores using a symmetrical 1,3,5-triaminobenzene ring as the center core for the connection of three fused DPAF-C2M moieties. The design led to a class of cis-cup-tris[(DPAF-C2M)-C60(>DPAF-C9)] 3D conformers with three bisadduct-analogous cages per nanomolecule facing at the same side of the geometrical molecular cis-cup-shape structure. A sequential synthetic route was described to afford this 3D configurated conformer in a high yield with various spectroscopic characterizations. In principle, a nanostructure with a non-coplanar 3D configuration in design should minimize the direct contact or π-stacking of fluorene rings with each other during molecular packing to the formation of fullerosome array. It may also prevent the self-quenching effect of its photoexcited states in solids. Photophysical properties of this cis-cup-conformer were also investigated.

Sodium nitrite potentiates antimicrobial photodynamic inactivation: possible involvement of peroxynitrate.

We have recently shown that a wide range of different inorganic salts can potentiate antimicrobial photodynamic inactivation (aPDI) and TiO2-mediated antimicrobial photocatalysis. Potentiation has been shown with azide, bromide, thiocyanate, selenocyanate, and most strongly, with iodide. Here we show that sodium nitrite can also potentiate broad-spectrum aPDI killing of Gram-positive MRSA and Gram-negative Escherichia coli bacteria. Literature reports have previously shown that two photosensitizers (PS), methylene blue (MB) and riboflavin, when excited by broad-band light in the presence of nitrite could lead to tyrosine nitration. Addition of up to 100 mM nitrite gave 6 logs of extra killing in the case of Rose Bengal excited by green light against E. coli, and 2 logs of extra killing against MRSA (eradication in both cases). Comparable results were obtained for other PS (TPPS4 + blue light and MB + red light). Some bacterial killing was obtained when bacteria were added after light using a functionalized fullerene (LC15) + nitrite + blue light, and tyrosine ester amide was nitrated using both "in" and "after" modes with all four PS. The mechanism could involve formation of peroxynitrate by a reaction between superoxide radicals and nitrogen dioxide radicals; formation of the latter species was demonstrated by spin trapping with nitromethane.

3D-Conformer of Tris[60]fullerenylated cis-Tris(diphenylamino-fluorene) as Photoswitchable Charge-Polarizer on GHz-Responsive Trilayered Core-Shell Dielectric Nanoparticles.

Novel 3D-configurated stereoisomers cis-cup-tris[C60>(DPAF-C9)] and trans-chair-tris[C60>(DPAF-C9)] were designed and synthesized in good yields. The former, with three C60> cages per molecule facing at the same side of the geometrical molecular cup-shape, was proposed to provide excellent binding interaction forces at the gold surface of core-shell γ-FeOx@AuNP nanoparticles and to direct the subsequent formation of a fullerene cage array (defined as fullerosome). Upon photoactivation of the Au-layer and cis-cup-tris[C60>(DPAF-C9)] itself, the degree of photoinduced intramolecular e--transfer from DPAF to a C60> moiety was found to be largely enhanced by the accumulated plasmonic resonance energy at the near-field surface. Distribution of resulting negative charges along the outer (C60>)-derived fullerosome shell layer of the trilayered NPs was correlated with the detected photoswitchable dielectric amplification phenomena using white LED light at 1.0 GHz.

Progressive cationic functionalization of chlorin derivatives for antimicrobial photodynamic inactivation and related vancomycin conjugates.

It is known that multiple cationic charges are required to produce broad-spectrum antimicrobial photosensitizers (PS) for photodynamic inactivation (aPDI) or photodynamic therapy of bacteria and fungi. In the present study we describe the synthesis and aPDI testing of a set of derivatives prepared from the parent pheophytin molecule with different numbers of attached side arms (1-3) each consisting of five quaternized cationic groups (pentacationic), producing the corresponding [Zn2+]pheophorbide-a-N(C2N+C1C3)5 (Zn-Phe-N5+, 5 charges), [Zn2+]chlorin e6-[N(C2N+C1C3)5]2 (Zn-Chl-N10+, 10 charges) and [Zn2+]mesochlorin e6-[N(C2N+C1C3)5]3 (Zn-mChl-N15+, 15 charges). Moreover, a conjugate between Zn-Phe-N5+ and the antibiotic vancomycin called Van-[Zn2+]-m-pheophorbide-N(C2N+C1C3)5 (Van-Zn-mPhe-N5+) was also prepared. The aPDI activities of all compounds were based on Type-II photochemistry (1O2 generation). We tested these compounds against Gram-positive methicillin-resistant Staphylococcus aureus (MRSA), Gram-negative Escherichia coli, and the fungal yeast Candida albicans. All three compounds were highly active against MRSA, giving eradication (≥6 logs of killing) with <1.0 µM and 10 J cm-2 of 415 nm light. The order of activity was Zn-Phe-N5+ > Zn-Chl-N10+ > Zn-mChl-N15+. In the case of E coli the activity was much lower (eradication was only possible with 50 µM Zn-mChl-N15+ and 20 J cm-2). The order of activity was the reverse of that found with MRSA (Zn-mChl-N15+ > Zn-Chl-N10+ > Zn-Phe-N5+). Activity against C. albicans was similar to E. coli with Zn-mChl-N15+ giving eradication. The activity of Van-Zn-mPhe-N5+ was generally lower than that of Zn-Phe-N5+ (except for E. coli). Red (660 nm) light was also effective as might be expected from the absorption spectra. An initial finding that Van-Zn-mPhe-N5+ might have higher activity against vancomycin resistant Enterococcus fecium (VRE) strains (compared to vancomycin sensitive strains) was disproved when it was found that VRE strains were also more sensitive to aPDI with Zn-Phe-N5+. The minimum inhibitory concentrations of Van-Zn-mPhe-N5+ were higher than those of Van alone, showing that the antibiotic properties of the Van moiety were lessened in the conjugate. In conclusion, Zn-Phe-N5+ is a highly active PS against Gram-positive species and deserves further testing. Increasing the number of cationic charges increased aPDI efficacy on C. albicans and Gram-negative E. coli.

Photodynamic Therapy with Hexa(sulfo-n-butyl)[60]Fullerene Against Sarcoma In Vitro and In Vivo.

The hydrophilic molecular micellar hexa(sulfo-n-butyl)[60]fullerene (FC4S), first synthesized in 1998 as a photosensitizer (PS) has been reported to exhibit high efficacy for singlet oxygen generation and antimicrobial photodynamic inactivation. The purpose of this study was to investigate the effects of photoactivated FC4S for free radical generation and to mediate photodynamic therapy (PDT) of cancer in vitro and in vivo. The results demonstrated that following light irradiation, FC4S produced singlet oxygen, but after addition of electron donors such as ferrocytochrome c or NADH, FC4S also produced superoxide. The combination of FC4S with light irradiation was able to induce cytotoxicity to human fibrosarcoma cells and murine sarcoma 180 cells in vitro. Cell-killing was proportional to fluence as well as FC4S concentration. Photoirradiation by argon-ion laser after intraperitoneal injection of FC4S also resulted in inhibition of S180 tumor growth in vivo (up to 80% reduction of tumor volume). Hematological and blood biochemistry parameters of the cancer-bearing mice were improved by PDT. Based on these findings, we conclude that FC4S has a great potential as a nanomedicine in PDT for cancer.

Broadband Two-Photon Absorption Characteristics of Highly Photostable Fluorenyl-Dicyanoethylenylated [60]Fullerene Dyads.

We synthesized four C60-(light-harvesting antenna) dyads C60 (>CPAF-Cn) (n = 4, 9, 12, or 18) 1-Cn for the investigation of their broadband nonlinear absorption effect. Since we have previously demonstrated their high function as two-photon absorption (2PA) materials at 1000 nm, a different 2PA wavelength of 780 nm was applied in the study. The combined data taken at two different wavelength ranges substantiated the broadband characteristics of 1-Cn. We proposed that the observed broadband absorptions may be attributed by a partial π-conjugation between the C60 > cage and CPAF-Cn moieties, via endinitrile tautomeric resonance, giving a resonance state with enhanced molecular conjugation. This transient state could increase its 2PA and excited-state absorption at 800 nm. In addition, a trend of concentration-dependent 2PA cross-section (σ2 ) and excited-state absorption magnitude was detected showing a higher σ value at a lower concentration that was correlated to increasing molecular separation with less aggregation for dyads C60(>CPAF-C18) and C60(>CPAF-C9), as better 2PA and excited-state absorbers.

Novel photoswitchable dielectric properties on nanomaterials of electronic core-shell γ-FeOx@Au@fullerosomes for GHz frequency applications.

We unexpectedly observed a large amplification of the dielectric properties associated with the photoswitching effect and the new unusual phenomenon of delayed photoinduced capacitor-like (i.e. electric polarization) behavior at the interface on samples of three-layered core-shell (γ-FeOx@AuNP)@[C60(>DPAF-C9)](n)2 nanoparticles (NPs) in frequencies of 0.5-4.0 GHz. The detected relative dielectric constant amplification was initiated upon switching off the light followed by relaxation to give an excellent recyclability. These NPs having e(-)-polarizable fullerosomic structures located at the outer layer were fabricated from highly magnetic core-shell γ-FeOx@AuNPs. Surface-stabilized 2 in a core-shell structure was found to be capable of photoinducing the surface plasmonic resonance (SPR) effect by white LED light. The accumulated SPR energy was subsequently transferred to the partially bilayered C60(>DPAF-C9) fullerosomic membrane layer in a near-field (∼1.5 nm) region without producing radiation heat. Since the monostatic SAR signal is dielectric property-dependent, we used these measurements to provide evidence of derived reflectivity changes on a surface coated with 2 at 0.5-4.0 GHz upon illumination of LED white light. We found that a high, >99%, efficiency of response amplification in image amplitude can be achieved.

Nanotechnology for photodynamic therapy: a perspective from the Laboratory of Dr. Michael R. Hamblin in the Wellman Center for Photomedicine at Massachusetts General Hospital and Harvard Medical School.

The research interests of the Hamblin Laboratory are broadly centered on the use of different kinds of light to treat many different diseases. Photodynamic therapy (PDT) uses the combination of dyes with visible light to produce reactive oxygen species and kill bacteria, cancer cells and destroy unwanted tissue. Likewise, UV light is also good at killing especially pathogens. By contrast, red or near-infrared light can have the opposite effect, to act to preserve tissue from dying and can stimulate healing and regeneration. In all these applications, nanotechnology is having an ever-growing impact. In PDT, self-assembled nano-drug carriers (micelles, liposomes, etc.) play a great role in solubilizing the photosensitizers, metal nanoparticles can carry out plasmon resonance enhancement, and fullerenes can act as photosensitizers, themselves. In the realm of healing, single-walled carbon nanotubes can be electrofocused to produce nano-electonic biomedical devices, and nanomaterials will play a great role in restorative dentistry.

Synthesis of Photoswitchable Magnetic Au-Fullerosome Hybrid Nanomaterials for Permittivity Enhancement Applications.

We designed and synthesized several nanomaterials 3 of three-layered core-shell (γ-FeOx@AuNP)@[C60(>DPAF-C9) 1 or 2]n nanoparticles (NPs). These NPs having e(-)-polarizable fullerosome structures located at the outer layer were fabricated from highly magnetic core-shell γ-FeOx@AuNPs. Fullerosomic polarization of 3 was found to be capable of causing a large amplification of material permittivity that is also associated with the photoswitching effect in the frequency range of 0.5-4.0 GHz. Multilayered synthetic construction allows Förster resonance energy transfer (FRET) of photoinduced accumulative surface plasmon resonance (SPR) energy in the gold layer to the partially bilayered C60(>DPAF-C9) 1 or 2-derived fullerosome membrane shell layer in a near-field of direct contact without producing radiation heat, which is commonly associated with SPR.

Synthesis and photoluminescent properties of geometrically hindered cis-tris(diphenylaminofluorene) as precursors to light-emitting devices.

A novel highly luminescent tris-fluorenyl ring-interconnected chromophore tris(DPAF-C9) was synthesized using a C3 symmetrical triaminobenzene core as the synthon. This structure bears three light-harvesting 2-diphenylamino-9,9-dialkylfluorenyl (DPAF) ring moieties with each attached by two branched 3',5',5'-trimethylhexyl (C9) arms. A major stereoisomer was chromatographically isolated and characterized to possess a 3D structural configuration of cis-conformer in a cup-form. Molecular calculation at B3LYP/6-31G* level revealed the unexpected stability of this cis-cup-conformer of tris(DPAF-C9) better than that of the stereoisomer in a propeller-form and the trans-conformer. The structural geometry is proposed to be capable of minimizing the aggregation related self-quenching effect in the condensed phase. Fluorescence emission wavelength of tris(DPAF-C9) was found to be in a close range to that of PVK that led to its potential uses as the secondary blue hole-transporting material for enhancing the device property toward the modulation of PLED performance.

Potentiation of antimicrobial photodynamic inactivation mediated by a cationic fullerene by added iodide: in vitro and in vivo studies.

BACKGROUND: Antimicrobial photodynamic inactivation with fullerenes bearing cationic charges may overcome resistant microbes. METHODS & RESULTS: We synthesized C60-fullerene (LC16) bearing decaquaternary chain and deca-tertiary-amino groups that facilitates electron-transfer reactions via the photoexcited fullerene. Addition of the harmless salt, potassium iodide (10 mM) potentiated the ultraviolet A (UVA) or white light-mediated killing of Gram-negative bacteria Acinetobacter baumannii, Gram-positive methicillin-resistant Staphylococcus aureus and fungal yeast Candida albicans by 1-2+ logs. Mouse model infected with bioluminescent Acinetobacter baumannii gave increased loss of bioluminescence when iodide (10 mM) was combined with LC16 and UVA/white light. CONCLUSION: The mechanism may involve photoinduced electron reduction of (1)(C60>)* or (3)(C60>)* by iodide producing I· or I2 followed by subsequent intermolecular electron-transfer events of (C60>)-· to produce reactive radicals.

Antimicrobial photodynamic inactivation with decacationic functionalized fullerenes: oxygen-independent photokilling in presence of azide and new mechanistic insights.

Functionalized fullerenes are gaining wide interest for mediating photodynamic therapy (PDT) of diseases such as cancers and infections. We recently reported the synthesis of two new decacationic fullerene monoadducts: C60[>M(C3N6(+)C3)2]-(I(-))10(LC14) and its derivative with a light-harvesting antenna conjugated as a C60[>CPAF-(MN6(+)C3)2]-(I(-))10 nanostructure (LC15). We studied the ability of these compounds to mediate PDT of human cancer cells in vitro when excited by UVA light or by white light. Here we report the synthesis of a new fullerene derivative C60[>M(C3N6(+)C3)2][>M(C3N6C3)2]-(I(-))10 (LC16 derived from LC14), as a malonate bisadduct containing a covalently bound decatertiary amine arm. We investigated the relative abilities of the three compounds to generate singlet oxygen ((1)O2), hydroxyl radicals (HO·), and hydrogen peroxide (H2O2) after excitation by UVA or by white light. We used three different classes of pathogenic microbial cells (Gram-positive bacterium, methicillin-resistant Staphylococcus aureus (MRSA), Gram-negative bacterium Escherichia coli, and fungal yeast Candida albicans). LC15 was the most powerful broad spectrum antimicrobial fullerenyl photosensitizer (FPS) followed by LC16, and LC14 was least powerful. Killing depended on both fullerene monoadduct concentration and light fluence. UVA was five times more effective than white light for killing, but not for generation of ROS and relative absorption was greater in white spectral region. Bacterial killing was not much inhibited by addition of azide anions and in some cases was potentiated. In the absence of oxygen, microbial photokilling was highly potentiated (up to 5 logs) by the addition of azide anions. We conclude that molecular functional addends that encourage a type I electron-transfer mechanism increase the ability of photoactivated fullerene monoadducts to kill microbial cells. Oxygen-independent photokilling is possible with fullerene monoadducts in the presence of azide anions, probably mediated by azidyl radicals. UVA excitation may kill bacteria partly by an electron-transfer mechanism directly into bacteria as well as by ROS.

Functionalized fullerenes in photodynamic therapy.

Since the discovery of C60 fullerene in 1985, scientists have been searching for biomedical applications of this most fascinating of molecules. The unique photophysical and photochemical properties of C60 suggested that the molecule would function well as a photosensitizer in photodynamic therapy (PDT). PDT uses the combination of non-toxic dyes and harmless visible light to produce reactive oxygen species that kill unwanted cells. However the extreme insolubility and hydrophobicity of pristine CO60, mandated that the cage be functionalized with chemical groups that provided water solubility and biological targeting ability. It has been found that cationic quaternary ammonium groups provide both these features, and this review covers work on the use of cationic fullerenes to mediate destruction of cancer cells and pathogenic microorganisms in vitro and describes the treatment of tumors and microbial infections in mouse models. The design, synthesis, and use of simple pyrrolidinium salts, more complex decacationic chains, and light-harvesting antennae that can be attached to C60, C70 and C84 cages are covered. In the case of bacterial wound infections mice can be saved from certain death by fullerene-mediated PDT.

Photodynamic therapy with decacationic [60]fullerene monoadducts: effect of a light absorbing electron-donor antenna and micellar formulation.

We report the synthesis and anticancer photodynamic properties of two new decacationic fullerene (LC14) and red light-harvesting antenna-fullerene conjugated monoadduct (LC15) derivatives. The antenna of LC15 was attached covalently to C60>with distance of only <3.0 Ǻ to facilitate ultrafast intramolecular photoinduced-electron-transfer (for type-I photochemistry) and photon absorption at longer wavelengths. Because LC15 was hydrophobic we compared formulation in Cremophor EL micelles with direct dilution from dimethylacetamide. LC14 produced more (1)O2 than LC15, while LC15 produced much more HO·than LC14 as measured by specific fluorescent probes. When delivered by DMA, LC14 killed more HeLa cells than LC15 when excited by UVA light, while LC15 killed more cells when excited by white light consistent with the antenna effect. However LC15 was more effective than LC14 when delivered by micelles regardless of the excitation light. Micellar delivery produced earlier apoptosis and damage to the endoplasmic reticulum as well as to lysosomes and mitochondria. FROM THE CLINICAL EDITOR: This team of authors report the synthesis and the photodynamic properties of two new derivatives for cancer treatment; one is a decacationic fullerene (LC14) and the other is a red light-harvesting antenna-fullerene conjugated monoadduct (LC15) utilizing a HeLa cell model.

Antimicrobial photodynamic therapy with decacationic monoadducts and bisadducts of [70]fullerene: in vitro and in vivo studies.

BACKGROUND: Antimicrobial photodynamic therapy uses photosensitizers designed to bind to microorganisms and generate reactive oxygen species when illuminated with visible light. MATERIALS & METHODS: We synthesized a highly water-soluble [70]fullerene monoadduct, C70[>M(C3N6(+)C3)2]-(I(-))10 (LC17), and bisadduct, C70[>M(C3N6(+)C3)2][>M(C3N6C3)2] (LC18), both with a well-defined decacationic quaternary ammonium iodide moiety with ten positive charges per C70 to give water solubility and bacterial binding. We determined the antimicrobial effects against human pathogens, Gram-positive (Staphylococcus aureus) and Gram-negative species (Escherichia coli and Acinetobacter baumannii) when activated by UVA or white light. RESULTS: White light was more effective with LC17, while UVA light was more effective with LC18. Both compounds were effective in a mouse model of Gram-negative third-degree burn infections determined by bioluminescence imaging. DISCUSSION & CONCLUSION: We propose that the attachment of an additional deca(tertiary-ethylenylamino)malonate arm to C70 allowed the moiety to act as a potent electron donor and increased the generation yield of hydroxyl radicals under UVA illumination.

Linear and Nonlinear Optical Properties of Photoresponsive [60]Fullerene Hybrid Triads and Tetrads with Dual NIR Two-Photon Absorption Characteristics.

Two C60-(antenna)x analogous compounds having branched hybrid triad C60(>DPAF-C18)(>CPAF-C2M) and tetrad C60(>DPAF-C18)(>CPAF-C2M)2 nanostructures were synthesized and characterized. The structural design was intended to facilitate the ultrafast fs intramolecular energy-transfer from photoexcited C60[>1(DPAF)*-C18](>CPAF-C2M)1or2 or C60(>DPAF-C18)[>1(CPAF)*-C2M]1or2 to the C60> cage moiety upon two-photon pumping at either 780 or 980 nm, respectively. The latter nanostructure showed approximately equal extinction coefficients of optical absorption over 400-550 nm that corresponds to near-IR two-photon based excitation wavelengths at 780-1100 nm for broadband nonlinear optical (NLO) applications. Aside from their enhanced two-photon absorption (2PA) activity at 780 nm, we also demonstrated ultrafast photo-responses at 980 nm showing 2PA cross-section (σ2) values of 995-1100 GM for the hybrid tetrad. These σ2 values were correlated to the observed good efficiency in reducing fs light-transmittance down to 35% at the light intensity of 110 GW/cm2. Accordingly, 2PA characteristics of these nanostructures at multiple NIR wavelengths provided support for their suitability in uses as broadband NLO nanomaterials at 600-1100 nm that includes the 2PA ability of two antenna, DPAF (700-850 nm) and CPAF (850-1100 nm), and the fullerene cage at shorter wavelengths (600-700 nm).

Synthesis of photoresponsive dual NIR two-photon absorptive [60]fullerene triads and tetrads.

Broadband nonlinear optical (NLO) organic nanostructures exhibiting both ultrafast photoresponse and a large cross-section of two-photon absorption throughout a wide NIR spectrum may make them suitable for use as nonlinear biophotonic materials. We report here the synthesis and characterization of two C60-(antenna)(x) analogous compounds as branched triad C60(>DPAF-C18)(>CPAF-C(2M)) and tetrad C60(>DPAF-C18)(>CPAF-C(2M))2 nanostructures. These compounds showed approximately equal extinction coefficients of optical absorption over 400-550 nm that corresponds to near-IR two-photon based excitation wavelengths at 780-1,100 nm. Accordingly, they may be utilized as potential precursor candidates to the active-core structures of photosensitizing nanodrugs for 2γ-PDT in the biological optical window of 800-1,050 nm.

Synthesis of decacationic [60]fullerene decaiodides giving photoinduced production of superoxide radicals and effective PDT-mediation on antimicrobial photoinactivation.

We report a novel class of highly water-soluble decacationic methano[60]fullerene decaiodides C60[>M(C3N6(+)C3)2]-(I(-))10 [1-(I(-))10] capable of co-producing singlet oxygen (Type-II) and highly reactive hydroxyl radicals, formed from superoxide radicals in Type-I photosensitizing reactions, upon illumination at both UVA and white light wavelengths. The O2(-)·-production efficiency of 1-(I(-))10 was confirmed by using an O2(-)·-reactive bis(2,4-dinitrobenzenesulfonyl)tetrafluorofluorescein probe and correlated to the photoinduced electron-transfer event going from iodide anions to (3)C60*[>M(C3N6(+)C3)2] leading to C60(-)·[>M(C3N6(+)C3)2]. Incorporation of a defined number (ten) of quaternary ammonium cationic charges per C60 in 1 was aimed to enhance its ability to target pathogenic Gram-positive and Gram-negative bacterial cells. We used the well-characterized malonato[60]fullerene diester monoadduct C60[>M(t-Bu)2] as the starting fullerene derivative to provide a better synthetic route to C60[>M(C3N6(+)C3)2] via transesterification reaction under trifluoroacetic acid catalyzed conditions. These compounds may be used as effective photosensitizers and nano-PDT drugs for photoinactivation of pathogens.

Photoinduced electron-transfer mechanisms for radical-enhanced photodynamic therapy mediated by water-soluble decacationic C70 and C84O2 Fullerene Derivatives.

Fullerenes are promising candidates for photodynamic therapy (PDT). Thus, C70 and novel C84O2 fullerenes were functionalized with and without an additional deca-tertiary ethyleneamino-chain as an electron source, giving rise to two distinct pairs of photosensitizers, the monoadducts LC-17, LC-19 and the bisadducts LC18 and LC-20 to perform PDT in HeLa cells with UVA, blue, green, white and red light. Shorter wavelengths gave more phototoxicity with LC-20 while LC-19 was better at longer wavelengths; the ratio between killing obtained with LC-19 and LC-20 showed an almost perfect linear correlation (R = 0.975) with wavelength. The incorporation of a deca-tertiary amine chain in the C84O2 fullerene gave more PDT killing when excited with shorter wavelengths or in the presence of low ascorbate concentration through higher generation of hydroxyl radicals. Photoactivated C84O2 fullerenes induced apoptosis of HeLa cancer cells, together with mitochondrial and lysosomal damage demonstrated by acridine orange and rhodamine 123 fluorescent probes. FROM THE CLINICAL EDITOR: Photoactivated C70 and C84O2 fullerenes were demonstrated to induce apoptosis of HeLa cancer cells, together with mitochondrial and lysosomal damage, as a function of wavelength. The study is paving the way to future clinical uses of these agents in photodynamic therapy.

Shining light on nanotechnology to help repair and regeneration.

Phototherapy can be used in two completely different but complementary therapeutic applications. While low level laser (or light) therapy (LLLT) uses red or near-infrared light alone to reduce inflammation, pain and stimulate tissue repair and regeneration, photodynamic therapy (PDT) uses the combination of light plus non-toxic dyes (called photosensitizers) to produce reactive oxygen species that can kill infectious microorganisms and cancer cells or destroy unwanted tissue (neo-vascularization in the choroid, atherosclerotic plaques in the arteries). The recent development of nanotechnology applied to medicine (nanomedicine) has opened a new front of advancement in the field of phototherapy and has provided hope for the development of nanoscale drug delivery platforms for effective killing of pathological cells and to promote repair and regeneration. Despite the well-known beneficial effects of phototherapy and nanomaterials in producing the killing of unwanted cells and promoting repair and regeneration, there are few reports that combine all three elements i.e. phototherapy, nanotechnology and, tissue repair and regeneration. However, these areas in all possible binary combinations have been addressed by many workers. The present review aims at highlighting the combined multi-model applications of phototherapy, nanotechnology and, reparative and regeneration medicine and outlines current strategies, future applications and limitations of nanoscale-assisted phototherapy for the management of cancers, microbial infections and other diseases, and to promote tissue repair and regeneration.