Development of Innovative Multistage Nanovectors for Cancer Immunotherapy

Flavia Fontana, Mohammad-Ali Shahbazi, Dongfei Liu, Hongbo Zhang, Ermei Mäkilä, Jarno Salonen, Jouni Tapio Hirvonen, Helder Almeida Santos

Forskningsoutput: KonferensbidragSammanfattningForskningPeer review

Sammanfattning

Introduction Cancers are is a very challenging diseases and new approaches are sought to help in their its treatment. Cancer immunotherapy involves the patient’s own immune system in the fight against the tumors using antibodies directed to the so-called “check-point inhibitors” or by the administration of chimeric T-lymphocytes. It is envisaged that the administration of nanoparticles in cancer vaccines would lead to a decrease in the side effects of the drugs, helping targeted drug delivery, and increase increasing the efficacy of the therapy due to the adjuvant properties of the particles themselves [1]. Porous silicon (PSi) is a biocompatible porous material which presents adjuvant-like properties [2]. Acetylated dextran (AcDX) and spermine-modified AcDX (SpAcDX) are chemically-modified polymers derived from dextran, a FDA approved material, able to stimulate an immune response by the activation of Toll-like receptors [3]. Methods Multistage nanovectors were prepared by nanoprecipitation during glass capillary microfluidics [4]. PSi nanoparticles were encapsulated in a polymeric matrix made of AcDEX. The immunostimulant properties of the nanoparticles were assessed in vitro on human immortalized immune cells and blood-derived monocytes . Results The developed nanosystems induced the expression of co-stimulatory factors (CD86) in, for example, peripheral blood monocytes (Fig.1). Figure 1 Percentage of CD86+ expression in a population of human peripheral blood monocytes after 72 h of incubation with the particles. TOPSi@AcDX are thermally oxidized PSi particles encapsulated inside an AcDEX shell; TOPSi@SpAcDX particles were encapsulated inside a spermine-modifed AcDEX shell; TOPSi@AcDX@CCM particles were further modified with membranes derived from MDA-MB-231 cancer cells. The levels of significance were set at p>0.05 (*) and p>0.01 (**); n = 3. Discussion The multistage nanovectors, produced with different polymers, promoted the expression of CD86 from human monocytes , KG 1, and BDCM (results not shown). Moreover, the system modified with membranes derived from cancer cells showed the highest levels of CDs stimulation, with a statistically significant difference compared to the particles with the polymer alone. Conclusions The developed systems promoted the expression of costimulatory factors (CD80) confirming their adjuvant properties that make them suitable platforms for further development as cancer vaccines. References [1] D.J. Irvine,M.C. Hanson, Synthetic Nanoparticles for Vaccines and Immunotherapy,115 Chemical Reviews (2015), 11109-46. [2] M.A. Shahbazi,T.D. Fernandez, Surface chemistry dependent immunostimulative potential of porous silicon nanoplatforms, Biomaterials 35 (33)(2014), 9224-35. [3] L. Cui,J.A. Cohen, Mannosylated dextran nanoparticles: a pH-sensitive system engineered for immunomodulation through mannose targeting, Bioconjug Chem 22 (5)(2011), 949-57. [4] D. Liu,S. Cito, A versatile and robust microfluidic platform toward high throughput synthesis of homogeneous nanoparticles with tunable properties, Adv Mater 27 (14)(2015), 2298-304. Acknowledgements Financial support from the Academy of Finland (Grants No. 252215 and 281300), the University of Helsinki Research Funds, the Biocentrum Helsinki, and the European Research Council (FP/2007-2013, Grant 310892) is greatly acknowledge.
Originalspråkengelska
StatusPublicerad - 30 sep 2016
EvenemangInternational Conference on Nanomedicine and Nanobiotechnology - University Pierre and Marie Curie, Paris, Frankrike
Varaktighet: 28 sep 201630 sep 2016
http://premc.org/iconan2016/

Konferens

KonferensInternational Conference on Nanomedicine and Nanobiotechnology
Förkortad titelICONAN 2016
LandFrankrike
OrtParis
Period28/09/201630/09/2016
Internetadress

Vetenskapsgrenar

  • 317 Farmaci

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Fontana, F., Shahbazi, M-A., Liu, D., Zhang, H., Mäkilä, E., Salonen, J., ... Almeida Santos, H. (2016). Development of Innovative Multistage Nanovectors for Cancer Immunotherapy. Abstract från International Conference on Nanomedicine and Nanobiotechnology, Paris, Frankrike.
Fontana, Flavia ; Shahbazi, Mohammad-Ali ; Liu, Dongfei ; Zhang, Hongbo ; Mäkilä, Ermei ; Salonen, Jarno ; Hirvonen, Jouni Tapio ; Almeida Santos, Helder. / Development of Innovative Multistage Nanovectors for Cancer Immunotherapy. Abstract från International Conference on Nanomedicine and Nanobiotechnology, Paris, Frankrike.
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title = "Development of Innovative Multistage Nanovectors for Cancer Immunotherapy",
abstract = "Introduction Cancers are is a very challenging diseases and new approaches are sought to help in their its treatment. Cancer immunotherapy involves the patient’s own immune system in the fight against the tumors using antibodies directed to the so-called “check-point inhibitors” or by the administration of chimeric T-lymphocytes. It is envisaged that the administration of nanoparticles in cancer vaccines would lead to a decrease in the side effects of the drugs, helping targeted drug delivery, and increase increasing the efficacy of the therapy due to the adjuvant properties of the particles themselves [1]. Porous silicon (PSi) is a biocompatible porous material which presents adjuvant-like properties [2]. Acetylated dextran (AcDX) and spermine-modified AcDX (SpAcDX) are chemically-modified polymers derived from dextran, a FDA approved material, able to stimulate an immune response by the activation of Toll-like receptors [3]. Methods Multistage nanovectors were prepared by nanoprecipitation during glass capillary microfluidics [4]. PSi nanoparticles were encapsulated in a polymeric matrix made of AcDEX. The immunostimulant properties of the nanoparticles were assessed in vitro on human immortalized immune cells and blood-derived monocytes . Results The developed nanosystems induced the expression of co-stimulatory factors (CD86) in, for example, peripheral blood monocytes (Fig.1). Figure 1 Percentage of CD86+ expression in a population of human peripheral blood monocytes after 72 h of incubation with the particles. TOPSi@AcDX are thermally oxidized PSi particles encapsulated inside an AcDEX shell; TOPSi@SpAcDX particles were encapsulated inside a spermine-modifed AcDEX shell; TOPSi@AcDX@CCM particles were further modified with membranes derived from MDA-MB-231 cancer cells. The levels of significance were set at p>0.05 (*) and p>0.01 (**); n = 3. Discussion The multistage nanovectors, produced with different polymers, promoted the expression of CD86 from human monocytes , KG 1, and BDCM (results not shown). Moreover, the system modified with membranes derived from cancer cells showed the highest levels of CDs stimulation, with a statistically significant difference compared to the particles with the polymer alone. Conclusions The developed systems promoted the expression of costimulatory factors (CD80) confirming their adjuvant properties that make them suitable platforms for further development as cancer vaccines. References [1] D.J. Irvine,M.C. Hanson, Synthetic Nanoparticles for Vaccines and Immunotherapy,115 Chemical Reviews (2015), 11109-46. [2] M.A. Shahbazi,T.D. Fernandez, Surface chemistry dependent immunostimulative potential of porous silicon nanoplatforms, Biomaterials 35 (33)(2014), 9224-35. [3] L. Cui,J.A. Cohen, Mannosylated dextran nanoparticles: a pH-sensitive system engineered for immunomodulation through mannose targeting, Bioconjug Chem 22 (5)(2011), 949-57. [4] D. Liu,S. Cito, A versatile and robust microfluidic platform toward high throughput synthesis of homogeneous nanoparticles with tunable properties, Adv Mater 27 (14)(2015), 2298-304. Acknowledgements Financial support from the Academy of Finland (Grants No. 252215 and 281300), the University of Helsinki Research Funds, the Biocentrum Helsinki, and the European Research Council (FP/2007-2013, Grant 310892) is greatly acknowledge.",
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Fontana, F, Shahbazi, M-A, Liu, D, Zhang, H, Mäkilä, E, Salonen, J, Hirvonen, JT & Almeida Santos, H 2016, 'Development of Innovative Multistage Nanovectors for Cancer Immunotherapy' International Conference on Nanomedicine and Nanobiotechnology, Paris, Frankrike, 28/09/2016 - 30/09/2016, .

Development of Innovative Multistage Nanovectors for Cancer Immunotherapy. / Fontana, Flavia; Shahbazi, Mohammad-Ali; Liu, Dongfei; Zhang, Hongbo; Mäkilä, Ermei; Salonen, Jarno ; Hirvonen, Jouni Tapio; Almeida Santos, Helder.

2016. Abstract från International Conference on Nanomedicine and Nanobiotechnology, Paris, Frankrike.

Forskningsoutput: KonferensbidragSammanfattningForskningPeer review

TY - CONF

T1 - Development of Innovative Multistage Nanovectors for Cancer Immunotherapy

AU - Fontana, Flavia

AU - Shahbazi, Mohammad-Ali

AU - Liu, Dongfei

AU - Zhang, Hongbo

AU - Mäkilä, Ermei

AU - Salonen, Jarno

AU - Hirvonen, Jouni Tapio

AU - Almeida Santos, Helder

PY - 2016/9/30

Y1 - 2016/9/30

N2 - Introduction Cancers are is a very challenging diseases and new approaches are sought to help in their its treatment. Cancer immunotherapy involves the patient’s own immune system in the fight against the tumors using antibodies directed to the so-called “check-point inhibitors” or by the administration of chimeric T-lymphocytes. It is envisaged that the administration of nanoparticles in cancer vaccines would lead to a decrease in the side effects of the drugs, helping targeted drug delivery, and increase increasing the efficacy of the therapy due to the adjuvant properties of the particles themselves [1]. Porous silicon (PSi) is a biocompatible porous material which presents adjuvant-like properties [2]. Acetylated dextran (AcDX) and spermine-modified AcDX (SpAcDX) are chemically-modified polymers derived from dextran, a FDA approved material, able to stimulate an immune response by the activation of Toll-like receptors [3]. Methods Multistage nanovectors were prepared by nanoprecipitation during glass capillary microfluidics [4]. PSi nanoparticles were encapsulated in a polymeric matrix made of AcDEX. The immunostimulant properties of the nanoparticles were assessed in vitro on human immortalized immune cells and blood-derived monocytes . Results The developed nanosystems induced the expression of co-stimulatory factors (CD86) in, for example, peripheral blood monocytes (Fig.1). Figure 1 Percentage of CD86+ expression in a population of human peripheral blood monocytes after 72 h of incubation with the particles. TOPSi@AcDX are thermally oxidized PSi particles encapsulated inside an AcDEX shell; TOPSi@SpAcDX particles were encapsulated inside a spermine-modifed AcDEX shell; TOPSi@AcDX@CCM particles were further modified with membranes derived from MDA-MB-231 cancer cells. The levels of significance were set at p>0.05 (*) and p>0.01 (**); n = 3. Discussion The multistage nanovectors, produced with different polymers, promoted the expression of CD86 from human monocytes , KG 1, and BDCM (results not shown). Moreover, the system modified with membranes derived from cancer cells showed the highest levels of CDs stimulation, with a statistically significant difference compared to the particles with the polymer alone. Conclusions The developed systems promoted the expression of costimulatory factors (CD80) confirming their adjuvant properties that make them suitable platforms for further development as cancer vaccines. References [1] D.J. Irvine,M.C. Hanson, Synthetic Nanoparticles for Vaccines and Immunotherapy,115 Chemical Reviews (2015), 11109-46. [2] M.A. Shahbazi,T.D. Fernandez, Surface chemistry dependent immunostimulative potential of porous silicon nanoplatforms, Biomaterials 35 (33)(2014), 9224-35. [3] L. Cui,J.A. Cohen, Mannosylated dextran nanoparticles: a pH-sensitive system engineered for immunomodulation through mannose targeting, Bioconjug Chem 22 (5)(2011), 949-57. [4] D. Liu,S. Cito, A versatile and robust microfluidic platform toward high throughput synthesis of homogeneous nanoparticles with tunable properties, Adv Mater 27 (14)(2015), 2298-304. Acknowledgements Financial support from the Academy of Finland (Grants No. 252215 and 281300), the University of Helsinki Research Funds, the Biocentrum Helsinki, and the European Research Council (FP/2007-2013, Grant 310892) is greatly acknowledge.

AB - Introduction Cancers are is a very challenging diseases and new approaches are sought to help in their its treatment. Cancer immunotherapy involves the patient’s own immune system in the fight against the tumors using antibodies directed to the so-called “check-point inhibitors” or by the administration of chimeric T-lymphocytes. It is envisaged that the administration of nanoparticles in cancer vaccines would lead to a decrease in the side effects of the drugs, helping targeted drug delivery, and increase increasing the efficacy of the therapy due to the adjuvant properties of the particles themselves [1]. Porous silicon (PSi) is a biocompatible porous material which presents adjuvant-like properties [2]. Acetylated dextran (AcDX) and spermine-modified AcDX (SpAcDX) are chemically-modified polymers derived from dextran, a FDA approved material, able to stimulate an immune response by the activation of Toll-like receptors [3]. Methods Multistage nanovectors were prepared by nanoprecipitation during glass capillary microfluidics [4]. PSi nanoparticles were encapsulated in a polymeric matrix made of AcDEX. The immunostimulant properties of the nanoparticles were assessed in vitro on human immortalized immune cells and blood-derived monocytes . Results The developed nanosystems induced the expression of co-stimulatory factors (CD86) in, for example, peripheral blood monocytes (Fig.1). Figure 1 Percentage of CD86+ expression in a population of human peripheral blood monocytes after 72 h of incubation with the particles. TOPSi@AcDX are thermally oxidized PSi particles encapsulated inside an AcDEX shell; TOPSi@SpAcDX particles were encapsulated inside a spermine-modifed AcDEX shell; TOPSi@AcDX@CCM particles were further modified with membranes derived from MDA-MB-231 cancer cells. The levels of significance were set at p>0.05 (*) and p>0.01 (**); n = 3. Discussion The multistage nanovectors, produced with different polymers, promoted the expression of CD86 from human monocytes , KG 1, and BDCM (results not shown). Moreover, the system modified with membranes derived from cancer cells showed the highest levels of CDs stimulation, with a statistically significant difference compared to the particles with the polymer alone. Conclusions The developed systems promoted the expression of costimulatory factors (CD80) confirming their adjuvant properties that make them suitable platforms for further development as cancer vaccines. References [1] D.J. Irvine,M.C. Hanson, Synthetic Nanoparticles for Vaccines and Immunotherapy,115 Chemical Reviews (2015), 11109-46. [2] M.A. Shahbazi,T.D. Fernandez, Surface chemistry dependent immunostimulative potential of porous silicon nanoplatforms, Biomaterials 35 (33)(2014), 9224-35. [3] L. Cui,J.A. Cohen, Mannosylated dextran nanoparticles: a pH-sensitive system engineered for immunomodulation through mannose targeting, Bioconjug Chem 22 (5)(2011), 949-57. [4] D. Liu,S. Cito, A versatile and robust microfluidic platform toward high throughput synthesis of homogeneous nanoparticles with tunable properties, Adv Mater 27 (14)(2015), 2298-304. Acknowledgements Financial support from the Academy of Finland (Grants No. 252215 and 281300), the University of Helsinki Research Funds, the Biocentrum Helsinki, and the European Research Council (FP/2007-2013, Grant 310892) is greatly acknowledge.

KW - 317 Pharmacy

KW - Nanotechnology

KW - vaccine

KW - cancer immunotherapy

KW - biohybrid

M3 - Abstract

ER -

Fontana F, Shahbazi M-A, Liu D, Zhang H, Mäkilä E, Salonen J et al. Development of Innovative Multistage Nanovectors for Cancer Immunotherapy. 2016. Abstract från International Conference on Nanomedicine and Nanobiotechnology, Paris, Frankrike.