Multifunctional Bioconjugated Gold Nanoparticles for...
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Multifunctional Bioconjugated Gold Nanoparticles for Cancer Theranostics Authors C2TN members: Francisco Silva 1,* , Paula Campello 1 , Lurdes Gano 1 , Fernanda Marques 1 , Pedro Santos 3 , Joana Guerreiro 1 , Ana Belchior 2 , António Paulo 1 *[email protected] Research group(s) Collaborations MU | Columbia, USA CNRS | Orléans, France UPO | Alessandria, Italy FCT-UNL | Caparica, Portugal CiiEM | Caparica, Portugal CTN/DECN | Bobadela, Portugal Thematic Strand Radiopharmaceutical Sciences & Health Physics Funding Introduction The field of nuclear medicine with the application of adequate instrumentation and radiopharmaceuticals has firmly demonstrated that it can offer unique means to study cancer biology and to optimize cancer therapy. In this context, gold nanoparticles (AuNPs) have emerged as attractive tools to develop innovative (nano)radiopharmaceuticals due to their appealing properties for medical application such as, biocompatibility, easy functionalization and good biological half-life. In the latest years, the Radiopharmaceuticals Sciences Group of C 2 TN has developed different multifunctional AuNPs for targeted delivery of radionuclides to tumor sites. These AuNPs are decorated with bombesin (BBN) peptide analogs to target the gastrin releasing peptide receptor, which is overexpressed in a variety of cancers including prostate cancer that is one of the tumors with highest incidence among male patients. These AuNPs were able to coordinate to medically relevant radiometals, like 67 Ga, for SPECT imaging and/or Gd for MRI. Additionally, they offer the possibility to be applied in anticancer therapies, namely as radiosensitizers profiting from the strong photoelectric absorption coefficient of the Au core or as nanoplatforms for image-guided drug delivery. Overall, this work is intended to provide scientific knowledge on the development of nanoplatforms for theranostic applications in cancer treatment, which in the future may help physicians to more efficiently treat this pathology and improve patients quality of life and life expectancy. Coordinated Gd - MRI Coordinated 67 Ga - SPECT BBN analog – GRPr targeting Gold core - Radiosensitisation AuNPs Structure Future Work • Study of the BBN-containing AuNPs as nanocarriers for the delivery of Pt(IV) prodrugs; • Evaluation of the therapeutic efficacy of the resulting multimodal AuNPs against prostate cancer using different imaging modalities (SPECT, CT or MRI) and exploring possible synergisms between different therapeutic modalities (chemotherapy, external and internal radiotherapy); • Design and pre-clinical evaluation of related AuNPs targeted at alternative receptors overexpressed in other aggressive human cancers (e.g. tachykinin type1 receptor in multiforme glioblastoma). Figure 6 - TEM image showing nanoparticles in the nucleus of prostate cancer PC3 cells after incubation with BBN-Au-TDOTA. Figure 2 – Affinity studies of the AuNPs through competitive binding assays with 125 I- BBN in prostate cancer PC3 cells, indicating a higher affinity for the BBN-containg AuNPs Keywords Radiopharmaceuticals Gold Nanoparticles Targeting Peptide Radiosensitization Figure 3 – Cellular uptake studies in prostate cancer PC3 cells of the 67 Ga-radiolabeled AuNPs, showing a much higher internalization for the BBN-containg AuNPs. Figure 4 – Biodistribution studies of BBN-Au-TDOTA- 67 Ga in prostate cancer PC3 xenograft Balb/c mice, showing a ≈ 4% uptake in the tumor, 24h post-injection. Figure 1 – TEM image and respective histogram showing the Au core size of 4-5 nm. Pre-Clinical Evaluation of the Radiolabeled AuNPs Figure 7 – Irradiation studies of prostate cancer PC3 and glioblastoma U87 cells, showing a higher cell death for the ones incubated with the AuNPs. (2 Gy radiation dose). Figure 5 – (Left) Phantom images and (Right) NMRD profile for Au-TDOTA-Gd and BBN–Au-TDOTA-Gd (25C), demonstrating the relaxivity properties of the Gd-containg AuNPs. Preliminary Evaluation as MRI Probes BBN-Au-TDOTA- 67 Ga Radiosensitization Properties F. Silva et al, Bioconjugate Chem., 2016, 27 (4), pp 1153–1164 http://c2tn.tecnico.ulisboa.pt RADIATION FOR SCIENCE AND SOCIETY C 2 TN/IST acknowledges Fundação para a Ciência e a Tecnologia for financial support under the project UID/Multi/04349/2013 1 RS | Radiopharmaceutical Sciences Group 2 RPS | Radiation Protection and Safety Group 3 REI | Radiation, Elements and Isotopes Group 4 NET | Nuclear Engineering and Techniques Group 5 QEf | f-element Chemistry Group 6 SS | Solid State Group
Transcript of Multifunctional Bioconjugated Gold Nanoparticles for...
Multifunctional BioconjugatedGold Nanoparticles for Cancer
Theranostics
AuthorsC2TN members: Francisco Silva1,*, Paula Campello1, Lurdes Gano1, Fernanda Marques1, Pedro Santos3, Joana Guerreiro1, Ana Belchior2, António Paulo1
Research group(s) CollaborationsMU | Columbia, USACNRS | Orléans, FranceUPO | Alessandria, ItalyFCT-UNL | Caparica, PortugalCiiEM | Caparica, PortugalCTN/DECN | Bobadela, Portugal
Thematic StrandRadiopharmaceutical Sciences & Health Physics
Funding
IntroductionThe field of nuclear medicine with the application of adequate instrumentation and radiopharmaceuticals has firmly demonstrated that it can offer unique means to study cancer
biology and to optimize cancer therapy. In this context, gold nanoparticles (AuNPs) have emerged as attractive tools to develop innovative (nano)radiopharmaceuticals due to
their appealing properties for medical application such as, biocompatibility, easy functionalization and good biological half-life.
In the latest years, the Radiopharmaceuticals Sciences Group of C2TN has developed different multifunctional AuNPs for targeted delivery of radionuclides to tumor sites. These
AuNPs are decorated with bombesin (BBN) peptide analogs to target the gastrin releasing peptide receptor, which is overexpressed in a variety of cancers including prostate
cancer that is one of the tumors with highest incidence among male patients. These AuNPs were able to coordinate to medically relevant radiometals, like 67Ga, for SPECT imaging
and/or Gd for MRI. Additionally, they offer the possibility to be applied in anticancer therapies, namely as radiosensitizers profiting from the strong photoelectric absorption
coefficient of the Au core or as nanoplatforms for image-guided drug delivery. Overall, this work is intended to provide scientific knowledge on the development of nanoplatforms
for theranostic applications in cancer treatment, which in the future may help physicians to more efficiently treat this pathology and improve patients quality of life and life
expectancy.
Coordinated Gd - MRI
Coordinated 67Ga - SPECT
BBN analog – GRPr targeting
Gold core - Radiosensitisation
AuNPs Structure
Future Work
• Study of the BBN-containing AuNPs as nanocarriers for the delivery of Pt(IV) prodrugs;• Evaluation of the therapeutic efficacy of the resulting multimodal AuNPs against prostate cancer using different imaging modalities (SPECT, CT or MRI) and exploring
possible synergisms between different therapeutic modalities (chemotherapy, external and internal radiotherapy);• Design and pre-clinical evaluation of related AuNPs targeted at alternative receptors overexpressed in other aggressive human cancers (e.g. tachykinin type1 receptor in
multiforme glioblastoma).
Figure 6 - TEM image showing nanoparticlesin the nucleus of prostate cancer PC3 cellsafter incubation with BBN-Au-TDOTA.
Figure 2 – Affinity studies of the AuNPsthrough competitive binding assays with 125I-BBN in prostate cancer PC3 cells, indicating ahigher affinity for the BBN-containg AuNPs
KeywordsRadiopharmaceuticals
Gold Nanoparticles
Targeting Peptide
Radiosensitization
Figure 3 – Cellular uptake studies in prostatecancer PC3 cells of the 67Ga-radiolabeled AuNPs,showing a much higher internalization for theBBN-containg AuNPs.
Figure 4 – Biodistribution studies of BBN-Au-TDOTA-67Ga inprostate cancer PC3 xenograft Balb/c mice, showing a ≈ 4% uptakein the tumor, 24h post-injection.
Figure 1 – TEM image and respective histogram showing the Au core size of 4-5 nm.
Pre-Clinical Evaluation of the Radiolabeled AuNPs
Figure 7 – Irradiation studies of prostate cancer PC3 andglioblastoma U87 cells, showing a higher cell death for theones incubated with the AuNPs. (2 Gy radiation dose).
Figure 5 – (Left) Phantom images and (Right) NMRD profile for Au-TDOTA-Gd and BBN–Au-TDOTA-Gd (25C),demonstrating the relaxivity properties of the Gd-containg AuNPs.
Preliminary Evaluation as MRI Probes
BBN-Au-TDOTA-67Ga
Radiosensitization Properties
F. Silva et al, Bioconjugate Chem., 2016, 27 (4), pp 1153–1164
http://c2tn.tecnico.ulisboa.ptRADIATION FOR SCIENCE AND SOCIETY
C2TN/IST acknowledgesFundação para a Ciência e a Tecnologia for
financial support under the projectUID/Multi/04349/2013
1 RS | Radiopharmaceutical Sciences Group2 RPS | Radiation Protection and Safety Group3 REI | Radiation, Elements and Isotopes Group4 NET | Nuclear Engineering and Techniques Group5 QEf | f-element Chemistry Group6 SS | Solid State Group
