Photofullerenes and Nanotechnology

2. In particular, our group works on the interface of nanotechnology and biology for clinical applications. In particular, nanoparticles are allowing us to develop tools that can work at the molecular level, even atom by atom, to, for example, deliver drugs and target cancers. We use nanoparticles for many reasons, including that they�re More stable: this is really good for drug delivery � because you probably want to administer the medication over a prolonged period of time Very flexible: can be customized, derivatized in many ways, given a broad range of properties Excellent administration to the body via oral, dermal, intravenous routes The tool that we focus on is photodynamic therapy. In particular, our group works on the interface of nanotechnology and biology for clinical applications. In particular, nanoparticles are allowing us to develop tools that can work at the molecular level, even atom by atom, to, for example, deliver drugs and target cancers. We use nanoparticles for many reasons, including that they�re More stable: this is really good for drug delivery � because you probably want to administer the medication over a prolonged period of time Very flexible: can be customized, derivatized in many ways, given a broad range of properties Excellent administration to the body via oral, dermal, intravenous routes The tool that we focus on is photodynamic therapy.

3. The tool that we are currently most interested and that�s been getting a lot of attention in is PDT. An area that is receiving much attention is the application of nanoparticles to photodynamic therapy or PDT. Photodynamic therapy is the use of visible and near-infrared light to treat disease. Briefly, it requires a source of radiation, a target tissue, a photosensitizer which is the nanoparticle, and molecular oxygen at ambient levels. How it works: a photosensitizer is administered to the target tissue, for example a cancerous tumour. Then light is shined onto the target tissue, which is absorbed by the photosensitizer and causes generation of reactive oxygen species. In a common mechanism, the photosensitizer moves from its ground state to an excited singlet state and then an excited triplet state. This triplet state is capable of generating singlet oxygen from molecular oxygen. Since singlet oxygen is highly reactive and cytotoxic, the tumour cells are destroyed.The tool that we are currently most interested and that�s been getting a lot of attention in is PDT. An area that is receiving much attention is the application of nanoparticles to photodynamic therapy or PDT. Photodynamic therapy is the use of visible and near-infrared light to treat disease. Briefly, it requires a source of radiation, a target tissue, a photosensitizer which is the nanoparticle, and molecular oxygen at ambient levels. How it works: a photosensitizer is administered to the target tissue, for example a cancerous tumour. Then light is shined onto the target tissue, which is absorbed by the photosensitizer and causes generation of reactive oxygen species. In a common mechanism, the photosensitizer moves from its ground state to an excited singlet state and then an excited triplet state. This triplet state is capable of generating singlet oxygen from molecular oxygen. Since singlet oxygen is highly reactive and cytotoxic, the tumour cells are destroyed.

4. PDT is advantageous in cancer treatment. Compared to complete excision of tumours by surgery, it is much less invasive. Compared to chemotherapy, its penetration limitations make it much less likely to damage underlying healthy cells. Success has been had especially for surface cancers of the skin and esophagus, by targeting tumour cells directly, their supporting vasculature, and activating the immune system. Other applications include treatment of skin diseases like psoriasis and in antimicrobial treatments.PDT is advantageous in cancer treatment. Compared to complete excision of tumours by surgery, it is much less invasive. Compared to chemotherapy, its penetration limitations make it much less likely to damage underlying healthy cells. Success has been had especially for surface cancers of the skin and esophagus, by targeting tumour cells directly, their supporting vasculature, and activating the immune system. Other applications include treatment of skin diseases like psoriasis and in antimicrobial treatments.

5. Design criteria: Be chemically pure and of known composition Localize to the target tissue Be activated and cytotoxic only in the presence of light Have high quantum yield for generation of singlet oxygen Absorb strongly at a specific wavelength with a large extinction coefficient This is best at the 600-800 range (visible light is 380-780 nm), where the depth of penetration ranges from 4 to 8 mm (maximum), while the energy of light is still strong enough to generate singlet oxygen. Design criteria: Be chemically pure and of known composition Localize to the target tissue Be activated and cytotoxic only in the presence of light Have high quantum yield for generation of singlet oxygen Absorb strongly at a specific wavelength with a large extinction coefficient This is best at the 600-800 range (visible light is 380-780 nm), where the depth of penetration ranges from 4 to 8 mm (maximum), while the energy of light is still strong enough to generate singlet oxygen.

6. So now we�re on the search for the perfect photosensitizer. And what we�re interested in is a family of molecules called fullerenes. Fullerenes were discovered in 1985 by a group of grad students from Rice University and the University of Sussex: Kroto, Curl, and Smalley. They vaporized carbon and then condensed it in an atmosphere of inert gas. The result was a new allotrope of carbon, C60. They were named buckminsterfullerenes or buckyballsSo now we�re on the search for the perfect photosensitizer. And what we�re interested in is a family of molecules called fullerenes. Fullerenes were discovered in 1985 by a group of grad students from Rice University and the University of Sussex: Kroto, Curl, and Smalley. They vaporized carbon and then condensed it in an atmosphere of inert gas. The result was a new allotrope of carbon, C60. They were named buckminsterfullerenes or buckyballs

7. So now we�re on the search for the perfect photosensitizer. And what we�re interested in is a family of molecules called fullerenes. Fullerenes were discovered in 1985 by a group of grad students from Rice University and the University of Sussex: Kroto, Curl, and Smalley. They vaporized carbon and then condensed it in an atmosphere of inert gas. The result was a new allotrope of carbon, C60. They were named buckminsterfullerenes or buckyballsSo now we�re on the search for the perfect photosensitizer. And what we�re interested in is a family of molecules called fullerenes. Fullerenes were discovered in 1985 by a group of grad students from Rice University and the University of Sussex: Kroto, Curl, and Smalley. They vaporized carbon and then condensed it in an atmosphere of inert gas. The result was a new allotrope of carbon, C60. They were named buckminsterfullerenes or buckyballs

9. A non-linear material is one for which the dielectric polarization (P � the responds nonlinearly to the electric field. � This effect in fullerenes is a result of the ease with which the excited singlet state transitions to the excited triplet state. From the earlier discussion, you can see why fullerenes are good starting blocks for designing photosensitizers that generate singlet oxygen. � Fullerenes are also advantageous because they exhibit two-photon absorption (TPA). Recall that species undergo electronic transitions when they absorb a photon with an amount of energy greater than the ionization energy. Large energy barriers may be surmounted if the species can simultaneously absorb two photons whose energies add together. TPA thus allows photodynamic therapy to be performed using lasers with longer wavelengths than the typical 600-800 nm, which is clinically safer. Longer wavelengths are less dangerous and display better penetration into tissues. � For example, compare titanium dioxide, a popular photosensitizer. It absorbs at much shorter wavelengths ~380 nm, which could damage surrounding tissues and shows much weaker penetration. A non-linear material is one for which the dielectric polarization (P � the responds nonlinearly to the electric field. � This effect in fullerenes is a result of the ease with which the excited singlet state transitions to the excited triplet state. From the earlier discussion, you can see why fullerenes are good starting blocks for designing photosensitizers that generate singlet oxygen. � Fullerenes are also advantageous because they exhibit two-photon absorption (TPA). Recall that species undergo electronic transitions when they absorb a photon with an amount of energy greater than the ionization energy. Large energy barriers may be surmounted if the species can simultaneously absorb two photons whose energies add together. TPA thus allows photodynamic therapy to be performed using lasers with longer wavelengths than the typical 600-800 nm, which is clinically safer. Longer wavelengths are less dangerous and display better penetration into tissues. � For example, compare titanium dioxide, a popular photosensitizer. It absorbs at much shorter wavelengths ~380 nm, which could damage surrounding tissues and shows much weaker penetration.

11. These factors can all affect the degree of molecular packing, which has been found to influence the multi-photon absorptivity of photofullerenes. In general, the closer the packing, the greater the tendency for excited singlet states to interact with surrounding ground state molecules, rather than generating singlet oxygen. Recent research in our lab on the previously-mentioned DPAF series used electron microscopy and zetasizers to characterize whether aggregation is a possible explanation for the . It was found that aggregation decreased with increased size (# antennae), increased concentration, and the use of the solvent CS2 vs. toluene. This corresponded to previous observations that these conditions increased 2PA. These findings could be significant in improving specificity and solubility of PDT photosensitizers and could also be useful in other applications such as superstructure design.These factors can all affect the degree of molecular packing, which has been found to influence the multi-photon absorptivity of photofullerenes. In general, the closer the packing, the greater the tendency for excited singlet states to interact with surrounding ground state molecules, rather than generating singlet oxygen. Recent research in our lab on the previously-mentioned DPAF series used electron microscopy and zetasizers to characterize whether aggregation is a possible explanation for the . It was found that aggregation decreased with increased size (# antennae), increased concentration, and the use of the solvent CS2 vs. toluene. This corresponded to previous observations that these conditions increased 2PA. These findings could be significant in improving specificity and solubility of PDT photosensitizers and could also be useful in other applications such as superstructure design.

12. These factors can all affect the degree of molecular packing, which has been found to influence the multi-photon absorptivity of photofullerenes. In general, the closet the packing, the greater the tendency for excited singlet states to interact with surrounding ground state molecules, rather than generating singlet oxygen. Recent research in our lab on the previously-mentioned DPAF series used electron microscopy and zetasizers to characterize aggregation. It was found that aggregation decreased with increased size (# antennae), increased concentration, and the use of the solvent CS2 vs. toluene. This corresponded to previous observations that these conditions increased 2PA. These findings could be significant in improving specificity and solubility of PDT photosensitizers and could also be useful in other applications such as superstructure design.These factors can all affect the degree of molecular packing, which has been found to influence the multi-photon absorptivity of photofullerenes. In general, the closet the packing, the greater the tendency for excited singlet states to interact with surrounding ground state molecules, rather than generating singlet oxygen. Recent research in our lab on the previously-mentioned DPAF series used electron microscopy and zetasizers to characterize aggregation. It was found that aggregation decreased with increased size (# antennae), increased concentration, and the use of the solvent CS2 vs. toluene. This corresponded to previous observations that these conditions increased 2PA. These findings could be significant in improving specificity and solubility of PDT photosensitizers and could also be useful in other applications such as superstructure design.

13. For example, we are currently studying the singlet oxygen quenching of a new compound called emerald green, synthesized by the Chiang group. We laser-excite mixtures of DPAF and quencher in toluene and measure the singlet oxygen emission at 1270 nm, and compare to known quenchers such as beta carotene. Beta carotene, found in many fruits and vegetables, is an excellent quencher of singlet oxygen because it has a large number of conjugated double bonds, causing triplet energy to be well below that of singlet oxygen. Excited oxygen is therefore removed by BC and excited BC readily dissipates the energy as heat.For example, we are currently studying the singlet oxygen quenching of a new compound called emerald green, synthesized by the Chiang group. We laser-excite mixtures of DPAF and quencher in toluene and measure the singlet oxygen emission at 1270 nm, and compare to known quenchers such as beta carotene. Beta carotene, found in many fruits and vegetables, is an excellent quencher of singlet oxygen because it has a large number of conjugated double bonds, causing triplet energy to be well below that of singlet oxygen. Excited oxygen is therefore removed by BC and excited BC readily dissipates the energy as heat.

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