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Nano Research 2015, 8(5): 1505-1521 https://doi.org/10.1007/s12274-014-0635-4
Research Article | Issue | Published: 03 December 2014

A prospective cancer chemo-immunotherapy approach mediated by synergistic CD326 targeted porous silicon nanovectors

Show Author's Information Mohammad-Ali Shahbazi1( ),  Neha Shrestha1,  Ermei Mäkilä1,2,  Francisca Araújo1,3,4,  Alexandra Correia1,  Tomás Ramos5,  Bruno Sarmento3,6,  Jarno Salonen2,  Jouni Hirvonen1,  Hélder A. Santos1( )
Division of Pharmaceutical Chemistry and TechnologyFaculty of PharmacyUniversity of HelsinkiFI-00014Helsinki, Finland
Laboratory of Industrial PhysicsDepartment of Physics and AstronomyUniversity of TurkuFI-20014Turku, Finland
INEB — Instituto de Engenharia BiomédicaNewTherapies GroupUniversidade do PortoRua do Campo Alegre823, 4150-180Porto, Portugal
ICBAS — Instituto Ciências Biomédicas Abel SalazarUniversity of PortoRua de Jorge Viterbo Ferreira4050-313Porto, Portugal
Faculty of PharmacyUniversity of Coimbra3000-548Coimbra, Portugal
IINFACTS – Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da SaúdeInstituto Superior de Ciências da Saúde-NorteDepartment of Pharmaceutical SciencesCESPU, Rua Central de Gandra4585-116Gandra, Portugal
Keywords:
breast cancer, CD326, antibody, porous silicon nanoparticles, chemo-immunotherapy, drug targeting
Cite this article:
Shahbazi M-A, Shrestha N, Mäkilä E, et al. A prospective cancer chemo-immunotherapy approach mediated by synergistic CD326 targeted porous silicon nanovectors. Nano Research, 2015, 8(5): 1505-1521. https://doi.org/10.1007/s12274-014-0635-4
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Abstract Full text Electronic supplementary material About this article

Combination therapy via nanoparticulate systems has already been proposed as a synergistic approach for cancer treatment. Herein, undecylenic acid modified thermally hydrocarbonized porous silicon nanoparticles (UnTHCPSi NPs) loaded with sorafenib and surface-biofunctionalized with anti-CD326 antibody (Ab) were developed for cancer chemo-immunotherapy in MCF-7 and MDA-MB-231 breast cancer cells. The cytocompatibility study showed no significant toxicity for the bare and antibody-conjugated UnTHCPSi (Un-Ab) NPs at concentrations lower than 200 μg·mL-1. Compared to the bare UnTHCPSi, Un-Ab NPs loaded with sorafenib reduced the premature drug release in plasma, increasing the probability of proper drug targeting. In addition, high cellular interaction and subsequent internalization of the Un-Ab NPs into the cells expressing CD326 antigen demonstrated the possibility of improving antigen-mediated endocytosis via CD326 targeting. While an in vitro antitumor study revealed a higher inhibitory effect of the sorafenib-loaded Un-Ab NPs compared to the drug-loaded UnTHCPSi NPs in the CD326 positive MCF-7 cells, there was no difference in the anti-proliferation impact of both the abovementioned NPs in the CD326 negative MDA-MB-231 cells, suggesting CD326 as an appropriate receptor for Ab-mediated drug delivery. It was also shown that the anti-CD326 Ab can act as an immunotherapeutic agent by inducing antibody dependent cellular cytotoxicity and enhancing the interaction of effector immune and cancer cells for subsequent phagocytosis and cytokine secretion. Hence, the developed nanovectors can be applied for simultaneous tumor-selective drug targeting and immunotherapy.


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Electronic supplementary material
About this article

A prospective cancer chemo-immunotherapy approach mediated by synergistic CD326 targeted porous silicon nanovectors

Show Author's information Mohammad-Ali Shahbazi1( ), Neha Shrestha1, Ermei Mäkilä1,2, Francisca Araújo1,3,4, Alexandra Correia1, Tomás Ramos5, Bruno Sarmento3,6, Jarno Salonen2, Jouni Hirvonen1, Hélder A. Santos1( )
Division of Pharmaceutical Chemistry and TechnologyFaculty of PharmacyUniversity of HelsinkiFI-00014Helsinki, Finland
Laboratory of Industrial PhysicsDepartment of Physics and AstronomyUniversity of TurkuFI-20014Turku, Finland
INEB — Instituto de Engenharia BiomédicaNewTherapies GroupUniversidade do PortoRua do Campo Alegre823, 4150-180Porto, Portugal
ICBAS — Instituto Ciências Biomédicas Abel SalazarUniversity of PortoRua de Jorge Viterbo Ferreira4050-313Porto, Portugal
Faculty of PharmacyUniversity of Coimbra3000-548Coimbra, Portugal
IINFACTS – Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da SaúdeInstituto Superior de Ciências da Saúde-NorteDepartment of Pharmaceutical SciencesCESPU, Rua Central de Gandra4585-116Gandra, Portugal

Abstract

Combination therapy via nanoparticulate systems has already been proposed as a synergistic approach for cancer treatment. Herein, undecylenic acid modified thermally hydrocarbonized porous silicon nanoparticles (UnTHCPSi NPs) loaded with sorafenib and surface-biofunctionalized with anti-CD326 antibody (Ab) were developed for cancer chemo-immunotherapy in MCF-7 and MDA-MB-231 breast cancer cells. The cytocompatibility study showed no significant toxicity for the bare and antibody-conjugated UnTHCPSi (Un-Ab) NPs at concentrations lower than 200 μg·mL-1. Compared to the bare UnTHCPSi, Un-Ab NPs loaded with sorafenib reduced the premature drug release in plasma, increasing the probability of proper drug targeting. In addition, high cellular interaction and subsequent internalization of the Un-Ab NPs into the cells expressing CD326 antigen demonstrated the possibility of improving antigen-mediated endocytosis via CD326 targeting. While an in vitro antitumor study revealed a higher inhibitory effect of the sorafenib-loaded Un-Ab NPs compared to the drug-loaded UnTHCPSi NPs in the CD326 positive MCF-7 cells, there was no difference in the anti-proliferation impact of both the abovementioned NPs in the CD326 negative MDA-MB-231 cells, suggesting CD326 as an appropriate receptor for Ab-mediated drug delivery. It was also shown that the anti-CD326 Ab can act as an immunotherapeutic agent by inducing antibody dependent cellular cytotoxicity and enhancing the interaction of effector immune and cancer cells for subsequent phagocytosis and cytokine secretion. Hence, the developed nanovectors can be applied for simultaneous tumor-selective drug targeting and immunotherapy.

Keywords: breast cancer, CD326, antibody, porous silicon nanoparticles, chemo-immunotherapy, drug targeting

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Publication history
Copyright
Acknowledgements

Publication history

Received: 23 July 2014
Revised: 31 October 2014
Accepted: 04 November 2014
Published: 03 December 2014
Issue date: May 2015

Copyright

© Tsinghua University Press and Springer-Verlag Berlin Heidelberg 2014

Acknowledgements

Acknowledgements

Dr. H. A. Santos acknowledges financial support from the Academy of Finland (decision Nos. 252215 and 256394), the University of Helsinki Research Funds, the Biocentrum Helsinki, and the European Research Council under the European Union's Seventh Framework Programme (FP/2007–2013) Grant No. 310892. Francisca Araújo would like to thank to FCT for financial support (SFRH/BD/87016/2012).

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