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

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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.

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Authors and Affiliations

  1. Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Helsinki, Finland

    Mohammad-Ali Shahbazi, Neha Shrestha, Ermei Mäkilä, Francisca Araújo, Alexandra Correia, Jouni Hirvonen & Hélder A. Santos

  2. Laboratory of Industrial Physics, Department of Physics and Astronomy, University of Turku, FI-20014, Turku, Finland

    Ermei Mäkilä & Jarno Salonen

  3. INEB — Instituto de Engenharia Biomédica, NewTherapies Group, Universidade do Porto, Rua do Campo Alegre, 823, 4150-180, Porto, Portugal

    Francisca Araújo & Bruno Sarmento

  4. ICBAS — Instituto Ciências Biomédicas Abel Salazar, University of Porto, Rua de Jorge Viterbo Ferreira, 4050-313, Porto, Portugal

    Francisca Araújo

  5. Faculty of Pharmacy, University of Coimbra, 3000-548, Coimbra, Portugal

    Tomás Ramos

  6. IINFACTS — Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Instituto Superior de Ciências da Saúde-Norte, Department of Pharmaceutical Sciences, CESPU, Rua Central de Gandra, 4585-116, Gandra, Portugal

    Bruno Sarmento

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  1. Mohammad-Ali Shahbazi
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  2. Neha Shrestha
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  3. Ermei Mäkilä
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  4. Francisca Araújo
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  6. Tomás Ramos
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  7. Bruno Sarmento
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  10. Hélder A. Santos
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Correspondence to Mohammad-Ali Shahbazi or Hélder A. Santos.

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Shahbazi, MA., Shrestha, N., Mäkilä, E. et al. A prospective cancer chemo-immunotherapy approach mediated by synergistic CD326 targeted porous silicon nanovectors. Nano Res. 8, 1505–1521 (2015). https://doi.org/10.1007/s12274-014-0635-4

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  • DOI: https://doi.org/10.1007/s12274-014-0635-4

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