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Functionalized mesoporous silica nanoparticles for two-photon photodynamic therapy
Oral Abstracts O114 Functionalized mesoporous silica nanoparticles for two-photon photodynamic therapy L. Raehm 1 , J.-O. Durand 1 , D. Brevet 1 , M. Gary-Bobo 2 , M. Garcia 2 , A. Morere 4 , O. Mongin 3 , M. Blanchard-Desce 3 , M. Maynadier 1 , I. Basile 1 , C. Rouxel 3 , Y. Mir 3 1
Institut Charles Gerhardt Montpellier, UMR 5253, Universite Montpellier2, France 2 IRCM, INSERM U896, CRCL, Montpellier, France 3 Chimie et Photonique Moléculaires, CNRS UMR 6510, Universite de Rennes, France 4 Institut des Biomoléculaires Max Mousseron, UMR 5247, ENSCM, Montpellier, France Photodynamic therapy combined with two-photon excitation (TPE) in the near infra red (NIR) region offers new perspectives for the ablation of solid tumours due to the increased penetration depth and unique 3D spatial resolution it provides. To enhance the selectivity towards tumour cells and the efficiency of PDT, photosensitizer encapsulation in nanoparticles is a promising route that has focused tremendous efforts. Mesoporous silica nanoparticles (MSN) hold great promise for cancer therapy as they are biocompatible and preferentially accumulate in tumours. We present a novel approach based on MSN in which new two-photon photosensitizers are covalently attached. These photosensitizers have much larger two-photon absorption cross-sections ( 2 ) than standard ones in the NIR region. In addition, the surface of the MSN is post-functionalized with mannose residues allowing for efficient targeting of lectins over-expressed by cancer cells. These tailored MSN were found to be very active in inducing cancer cell death upon short (typically 3 s) two-photon excitation at 760 nm when incubated with colon (HCT-116), retinoblastoma (Y-79) and breast (MCF-7, MDA-MB-231) cancer cells. These MSN were also tested for in vivo two-photon photodynamic therapy. A 70% regression of tumour size upon single treatment was observed in athymic mice bearing HCT-116 colon tumour xenografts. In addition, this treatment impaired the development of metastases associated with cancer spreading. This therapeutic approach could be particularly suited in the setting of localized small solid tumours whose detection has dramatically increased with routine cancer screening. doi:10.1016/j.pdpdt.2011.03.119 O115 PEGylated poly(lactide-co-glycolide) nanoparticles loaded with meta-tetra(hydroxyphenyl)chlorin for photodynamic treatment of cancer F. Moret 1 , C. Compagnin 1 , M. Rojnik 2 , P. Kocbek 2 , L. Celotti 1 , J. Kos 2 , E. Reddi 1 1 2
University of Padova, Department of Biology, Padova, Italy University of Ljubljana, Faculty of Pharmacy, Ljubljana, Slovenia
One of the most attractive applications of nanotechnology is the use of different types of nanoparticles (NPs) as vehicles for anticancer drugs in order to improve drug bioavailability, reduce cytotoxicity and enhance the precision of the delivery. The surface of the nanovehicles may be coated with polyethylenglycol (PEG) to minimize cytotoxicity and NP capture by the macrophages of the reticulo-endothelial system. In addition, NPs may be functionalized on the surface with specific ligands/antibodies recognized by receptors/antigens over-expressed in tumours, minimising drug accumulation in healthy tissues. Using nanoprecipitation method, we prepared biodegradable un-PEGylated and PEGylated poly(lactide-co-glycolide) NPs (PLGA NPs) loaded with the hydrophobic photosensitizer meta-tetra(hydroxyphenyl)chlorin
159 (mTHPC). We performed an in vitro study in different cell lines (A549, CCD-34Lu, MCF10A neoT, U937) comparing dark cytotoxicity, uptake, intracellular localization and photodynamic efficiency of mTHPC delivered in PLGA NPs. Cytotoxicity of mTHPC delivered by NPs was slightly reduced, due to the lower extent of the uptake with respect to the free drug, but must be completely attributed to mTHPC since the nanocarriers were demonstrated to be biocompatible. PEGylation significantly reduced the uptake of NPs by all of the selected cell lines, especially by the differentiated pro-monocytic U937. Furthermore, PEGylation decreased the intracellular degradation of PLGA matrix. Photodynamic efficiency was not affected by the presence of the nanovehicles, confirming the capability of mTHPC entrapped in PLGA NPs to produce singlet oxygen. Although we observed a time-dependent drug release from NPs in the presence of serum proteins, targeted PLGA NPs are proposed as carriers for mTHPC. Acknowledgements: This project received research funding from EU’s Seventh Framework Programme, Grant 201031 NANOPHOTO. doi:10.1016/j.pdpdt.2011.03.120 O116 Up-converting NaxLiyYF4:Yb3+, Er3+ nanocrystals functionalized with protoporphyrin IX as a potential drug in photodynamic therapy for cancer treatment T. Stuchinskaya 1,2,3 , D. Russell 1,2,3 , T. Nann 1,2,3 , D. Bavykin 1,2,3 1
University of East Anglia, Department of Chemistry, Norwich, UK University of South Australia, Ian Wark Research Institute, Adelaide, Australia 3 University of Southampton, School of Engineering Science, Southampton, UK 2
Upconverting nanoparticles have shown great potential for use in biological applications [1]. When a photosensitizer is attached to their surface the upconverting nanocrystals can generate reactive oxygen species under irradiation with low energy near infrared light. The particles itself are not soluble in water, surface modification is required for biological applications; another challenge is to improve the upconverting efficiency of the nanocrystals. To address these issues, we have introduced Li+ ions into the NaYF4 :Yb3+ , Er3+ nanocrystals lattice by substitution of some sites of the Na+ ions during nucleation to enhance the upconversion efficiency [2]. The surface of nanocrystals was modified with a silica coating: a photosensitizer, protoporphyrin IX, was silyl-functionalized via reaction with oxalyl chloride [3] and then covalently incorporated into the silica matrix by using a conventional sol—gel method [4]. In vitro experiments with cancer cells and measurement of singlet oxygen produced by the photosensitizer under infrared irradiation at 980 nm are in progress.
References [1] Chatterjee DK, Fong LS, Zhang Y. Adv Drug Deliv Rev 2008;60:1627—37. [2] Wang HQ, Nann T. ACS Nano 2009;3:3804—8. [3] Rossi LM, Silva PR, Vono LLR, Fernandes AU, Tada DB, Baptista MS. Langmuir 2008;24:12534—8. [4] Johnson NJJ, Sangeetha NM, Boyer JC, Van Veggel FCJM. Nanoscale 2010;2:771—7. doi:10.1016/j.pdpdt.2011.03.121
Institut Charles Gerhardt Montpellier, UMR 5253, Universite Montpellier2, France 2 IRCM, INSERM U896, CRCL, Montpellier, France 3 Chimie et Photonique Moléculaires, CNRS UMR 6510, Universite de Rennes, France 4 Institut des Biomoléculaires Max Mousseron, UMR 5247, ENSCM, Montpellier, France Photodynamic therapy combined with two-photon excitation (TPE) in the near infra red (NIR) region offers new perspectives for the ablation of solid tumours due to the increased penetration depth and unique 3D spatial resolution it provides. To enhance the selectivity towards tumour cells and the efficiency of PDT, photosensitizer encapsulation in nanoparticles is a promising route that has focused tremendous efforts. Mesoporous silica nanoparticles (MSN) hold great promise for cancer therapy as they are biocompatible and preferentially accumulate in tumours. We present a novel approach based on MSN in which new two-photon photosensitizers are covalently attached. These photosensitizers have much larger two-photon absorption cross-sections ( 2 ) than standard ones in the NIR region. In addition, the surface of the MSN is post-functionalized with mannose residues allowing for efficient targeting of lectins over-expressed by cancer cells. These tailored MSN were found to be very active in inducing cancer cell death upon short (typically 3 s) two-photon excitation at 760 nm when incubated with colon (HCT-116), retinoblastoma (Y-79) and breast (MCF-7, MDA-MB-231) cancer cells. These MSN were also tested for in vivo two-photon photodynamic therapy. A 70% regression of tumour size upon single treatment was observed in athymic mice bearing HCT-116 colon tumour xenografts. In addition, this treatment impaired the development of metastases associated with cancer spreading. This therapeutic approach could be particularly suited in the setting of localized small solid tumours whose detection has dramatically increased with routine cancer screening. doi:10.1016/j.pdpdt.2011.03.119 O115 PEGylated poly(lactide-co-glycolide) nanoparticles loaded with meta-tetra(hydroxyphenyl)chlorin for photodynamic treatment of cancer F. Moret 1 , C. Compagnin 1 , M. Rojnik 2 , P. Kocbek 2 , L. Celotti 1 , J. Kos 2 , E. Reddi 1 1 2
University of Padova, Department of Biology, Padova, Italy University of Ljubljana, Faculty of Pharmacy, Ljubljana, Slovenia
One of the most attractive applications of nanotechnology is the use of different types of nanoparticles (NPs) as vehicles for anticancer drugs in order to improve drug bioavailability, reduce cytotoxicity and enhance the precision of the delivery. The surface of the nanovehicles may be coated with polyethylenglycol (PEG) to minimize cytotoxicity and NP capture by the macrophages of the reticulo-endothelial system. In addition, NPs may be functionalized on the surface with specific ligands/antibodies recognized by receptors/antigens over-expressed in tumours, minimising drug accumulation in healthy tissues. Using nanoprecipitation method, we prepared biodegradable un-PEGylated and PEGylated poly(lactide-co-glycolide) NPs (PLGA NPs) loaded with the hydrophobic photosensitizer meta-tetra(hydroxyphenyl)chlorin
159 (mTHPC). We performed an in vitro study in different cell lines (A549, CCD-34Lu, MCF10A neoT, U937) comparing dark cytotoxicity, uptake, intracellular localization and photodynamic efficiency of mTHPC delivered in PLGA NPs. Cytotoxicity of mTHPC delivered by NPs was slightly reduced, due to the lower extent of the uptake with respect to the free drug, but must be completely attributed to mTHPC since the nanocarriers were demonstrated to be biocompatible. PEGylation significantly reduced the uptake of NPs by all of the selected cell lines, especially by the differentiated pro-monocytic U937. Furthermore, PEGylation decreased the intracellular degradation of PLGA matrix. Photodynamic efficiency was not affected by the presence of the nanovehicles, confirming the capability of mTHPC entrapped in PLGA NPs to produce singlet oxygen. Although we observed a time-dependent drug release from NPs in the presence of serum proteins, targeted PLGA NPs are proposed as carriers for mTHPC. Acknowledgements: This project received research funding from EU’s Seventh Framework Programme, Grant 201031 NANOPHOTO. doi:10.1016/j.pdpdt.2011.03.120 O116 Up-converting NaxLiyYF4:Yb3+, Er3+ nanocrystals functionalized with protoporphyrin IX as a potential drug in photodynamic therapy for cancer treatment T. Stuchinskaya 1,2,3 , D. Russell 1,2,3 , T. Nann 1,2,3 , D. Bavykin 1,2,3 1
University of East Anglia, Department of Chemistry, Norwich, UK University of South Australia, Ian Wark Research Institute, Adelaide, Australia 3 University of Southampton, School of Engineering Science, Southampton, UK 2
Upconverting nanoparticles have shown great potential for use in biological applications [1]. When a photosensitizer is attached to their surface the upconverting nanocrystals can generate reactive oxygen species under irradiation with low energy near infrared light. The particles itself are not soluble in water, surface modification is required for biological applications; another challenge is to improve the upconverting efficiency of the nanocrystals. To address these issues, we have introduced Li+ ions into the NaYF4 :Yb3+ , Er3+ nanocrystals lattice by substitution of some sites of the Na+ ions during nucleation to enhance the upconversion efficiency [2]. The surface of nanocrystals was modified with a silica coating: a photosensitizer, protoporphyrin IX, was silyl-functionalized via reaction with oxalyl chloride [3] and then covalently incorporated into the silica matrix by using a conventional sol—gel method [4]. In vitro experiments with cancer cells and measurement of singlet oxygen produced by the photosensitizer under infrared irradiation at 980 nm are in progress.
References [1] Chatterjee DK, Fong LS, Zhang Y. Adv Drug Deliv Rev 2008;60:1627—37. [2] Wang HQ, Nann T. ACS Nano 2009;3:3804—8. [3] Rossi LM, Silva PR, Vono LLR, Fernandes AU, Tada DB, Baptista MS. Langmuir 2008;24:12534—8. [4] Johnson NJJ, Sangeetha NM, Boyer JC, Van Veggel FCJM. Nanoscale 2010;2:771—7. doi:10.1016/j.pdpdt.2011.03.121