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Photosensitiser-nanoparticle conjugates for targeted PDT
158 Example photosensitizers used are photophrin, methylene blue and HPPH [3-(1 -hexyloxyethyl)pyropheophorbide-a]. Example in vivo applications include 9L-glioma (rats and rat cranial window model) and colon-26 (mice). These show good promise for PDT treatment of tumors in internal organs. doi:10.1016/j.pdpdt.2011.03.115 O110 Enhanced photodynamic therapy using NIR-to-visible upconversion fluorescent nanoparticles Y. Zhang, N.M. Idris National University of Singapore, Division of Bioengineering, Singapore Introduction: Photodynamic therapy (PDT) has proved effective in the treatment of early lung cancer, Barrett’s esophagus, bladder cancer, head and neck cancers, and to be the ideal treatment for skin cancer. Unfortunately, most of the photosensitizers used in conventional PDT can only be activated by visible light which cannot pass through a thick tissue. Hence, their application is still limited to treating tumors on or just under the skin, or on the lining of internal organs or cavities, and becomes less effective in treating large tumors. Use of NIR light in PDT can afford penetration depths of an order of magnitude greater than that of visible light, besides being less harmful to cells and tissues, hence reducing the risk of inadvertent tissue destruction. In our lab, NIR-to-visible upconversion fluorescent nanoparticles have been developed and used in PDT as a light transducer [1,2]. Method: Upconversion nanoparticles are coated with a layer of mesoporous silica to form a core—shell structure. The silica layer, being porous and having a large surface area, serves as a coating to encapsulate or contain the photosensitizer molecules. Results: The upconversion nanoparticles convert NIR light to visible light which activate the photosensitizers to release reactive oxygen species. The usefulness of the nanoparticles for non-invasive imaging of deep tissues and PDT have been demonstrated. Conclusion: It is foreseen that this concept of upconversion PDT may not only bring PDT to a new level of improved therapeutic index but also greater depths to treat large or deep-seated tumors.
References [1] Li ZQ, Zhang Y, Jiang S. Multicolor core/shell-structured upconversion fluorescent nanoparticles. Adv Mater 2008;20(24):4765—9. [2] Qian H, Guo H, Ho P, Mahendran R, Zhang Y. Mesoporous-silicacoated up-conversion fluorescent nanoparticles for photodynamic therapy. Small 2009;5(20):2285—90. doi:10.1016/j.pdpdt.2011.03.116 O111 Photosensitiser-nanoparticle conjugates for targeted PDT D. Russell University of East Anglia, School of Chemistry, Norwich, UK Gold nanoparticle conjugates have been designed and synthesised for the delivery of hydrophobic photosensitisers for photodynamic therapy (PDT) of cancer. For our work, we use a Zn(II) phthalocyanine derivative that is specifically structured to enable self-assembly of the hydrophobic photosensitiser on the surface of the gold nanoparticles. Our initial work focused on a synthetic strategy in which a phase transfer reagent interdigitates between
Oral Abstracts phthalocyanine molecules on the nanoparticle surface. Such nanoparticle conjugates were soluble in polar solvents, were efficient singlet oxygen generators and elicited excellent cell kill with the HeLa cervical cancer cell line. PDT studies in vivo demonstrated that these conjugates significantly decreased the rate of growth of a sub-cutaneously implanted amelanotic melanoma in a mouse model. Recently we have produced conjugates that have both the phthalocyanine derivative and a polyethylene glycol (PEG) selfassembled on the gold nanoparticle surface. These nanoparticle conjugates are water soluble and are stable in buffered media. These water soluble conjugates have been used in vivo for PDT studies with the sub-cutaneously implanted amelanotic melanoma. Excellent results have been obtained. Most recently, a monoclonal antibody has been covalently attached to the phthalocyanine nanoparticle conjugates. Attachment of an anti-HER2 antibody to the phthalocyanine nanoparticle conjugates leads to enhanced drug targeting of breast cancer cells that over express the HER2 receptor on the cellular surface. These phthalocyanine-nanoparticle conjugates have been shown to be exceptionally versatile and excellent agents for photodynamic therapy. doi:10.1016/j.pdpdt.2011.03.117 O113 Strategies to enhance drug delivery and targeting in photodynamic therapy to improve treatment outcome M. Olivo 1,2 1
School of Physics, National University of Ireland, Galway, Ireland Department of Pharmacy, National University of Singapore, No. 18 Science Drive 4, Singapore 2
Background: Photodynamic therapy (PDT) is an emerging modality for the treatment of various neoplastic and non-neoplastic pathologies. It is a targeted therapy that involves a tumor-localized photosensitizer, which is activated with light of specific wavelength resulting in the production of reactive oxygen species (ROS), leading to cell death. Though PDT is a selective modality, combining other targeted approaches can further enhance the treatment efficacy. Methods: During PDT, tumor vasculature can be targeted by using vascular disrupting and anti-angiogenesis agents. PDT can also activate the body’s immune response against tumors. By using specific synthetic peptides and gold nanoparticles as drug carriers, the photosensitizers can be delivered to the tumor site in a more selective manner with low toxicity, rendering minimal damage to the normal tissues. Results: Vascular-targeting PDT and anti-angiogenesis therapy have been successfully used along with PDT to enhance tumor response. Numerous preclinical and clinical observations have demonstrated the role of PDT induced activation of the body’s immune response against tumors. Synthetic peptides and gold nanoparticles have made reasonable progress in the recent years to achieve a certain degree of selectivity by site-specifically confining the photosensitizer, and thereby increasing the efficacy of PDT. Conclusion: Targeting approaches such as improved delivery of photosensitizers, selective vascular damage and tactical finetuning of light dosimetry to elicit an effective immune response can improve treatment outcome and bring PDT to the forefront of cancer therapeutics. doi:10.1016/j.pdpdt.2011.03.118
References [1] Li ZQ, Zhang Y, Jiang S. Multicolor core/shell-structured upconversion fluorescent nanoparticles. Adv Mater 2008;20(24):4765—9. [2] Qian H, Guo H, Ho P, Mahendran R, Zhang Y. Mesoporous-silicacoated up-conversion fluorescent nanoparticles for photodynamic therapy. Small 2009;5(20):2285—90. doi:10.1016/j.pdpdt.2011.03.116 O111 Photosensitiser-nanoparticle conjugates for targeted PDT D. Russell University of East Anglia, School of Chemistry, Norwich, UK Gold nanoparticle conjugates have been designed and synthesised for the delivery of hydrophobic photosensitisers for photodynamic therapy (PDT) of cancer. For our work, we use a Zn(II) phthalocyanine derivative that is specifically structured to enable self-assembly of the hydrophobic photosensitiser on the surface of the gold nanoparticles. Our initial work focused on a synthetic strategy in which a phase transfer reagent interdigitates between
Oral Abstracts phthalocyanine molecules on the nanoparticle surface. Such nanoparticle conjugates were soluble in polar solvents, were efficient singlet oxygen generators and elicited excellent cell kill with the HeLa cervical cancer cell line. PDT studies in vivo demonstrated that these conjugates significantly decreased the rate of growth of a sub-cutaneously implanted amelanotic melanoma in a mouse model. Recently we have produced conjugates that have both the phthalocyanine derivative and a polyethylene glycol (PEG) selfassembled on the gold nanoparticle surface. These nanoparticle conjugates are water soluble and are stable in buffered media. These water soluble conjugates have been used in vivo for PDT studies with the sub-cutaneously implanted amelanotic melanoma. Excellent results have been obtained. Most recently, a monoclonal antibody has been covalently attached to the phthalocyanine nanoparticle conjugates. Attachment of an anti-HER2 antibody to the phthalocyanine nanoparticle conjugates leads to enhanced drug targeting of breast cancer cells that over express the HER2 receptor on the cellular surface. These phthalocyanine-nanoparticle conjugates have been shown to be exceptionally versatile and excellent agents for photodynamic therapy. doi:10.1016/j.pdpdt.2011.03.117 O113 Strategies to enhance drug delivery and targeting in photodynamic therapy to improve treatment outcome M. Olivo 1,2 1
School of Physics, National University of Ireland, Galway, Ireland Department of Pharmacy, National University of Singapore, No. 18 Science Drive 4, Singapore 2
Background: Photodynamic therapy (PDT) is an emerging modality for the treatment of various neoplastic and non-neoplastic pathologies. It is a targeted therapy that involves a tumor-localized photosensitizer, which is activated with light of specific wavelength resulting in the production of reactive oxygen species (ROS), leading to cell death. Though PDT is a selective modality, combining other targeted approaches can further enhance the treatment efficacy. Methods: During PDT, tumor vasculature can be targeted by using vascular disrupting and anti-angiogenesis agents. PDT can also activate the body’s immune response against tumors. By using specific synthetic peptides and gold nanoparticles as drug carriers, the photosensitizers can be delivered to the tumor site in a more selective manner with low toxicity, rendering minimal damage to the normal tissues. Results: Vascular-targeting PDT and anti-angiogenesis therapy have been successfully used along with PDT to enhance tumor response. Numerous preclinical and clinical observations have demonstrated the role of PDT induced activation of the body’s immune response against tumors. Synthetic peptides and gold nanoparticles have made reasonable progress in the recent years to achieve a certain degree of selectivity by site-specifically confining the photosensitizer, and thereby increasing the efficacy of PDT. Conclusion: Targeting approaches such as improved delivery of photosensitizers, selective vascular damage and tactical finetuning of light dosimetry to elicit an effective immune response can improve treatment outcome and bring PDT to the forefront of cancer therapeutics. doi:10.1016/j.pdpdt.2011.03.118