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Nano Research

Article Title

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

Authors

Mohammad-Ali Shahbazi, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland
Neha Shrestha, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland
Ermei Mkil, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland Laboratory of Industrial Physics, Department of Physics and Astronomy, University of Turku, FI-20014 Turku, Finland
Francisca Araújo, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland INEB – Instituto de Engenharia Biomédica, NewTherapies Group, Universidade do Porto, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal ICBAS – Instituto Ciências Biomédicas Abel Salazar, University of Porto, Rua de Jorge Viterbo Ferreira, 4050-313 Porto, Portugal
Alexandra Correia, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland
Tomás Ramos, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal
Bruno Sarmento, INEB – Instituto de Engenharia Biomédica, NewTherapies Group, Universidade do Porto, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal IINFACTS – Instituto de Investigao e Formao Avanada 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
Jarno Salonen, Laboratory of Industrial Physics, Department of Physics and Astronomy, University of Turku, FI-20014 Turku, Finland
Jouni Hirvonen, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland
Hélder A. Santos, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland

Keywords

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

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.

Graphical Abstract

Publisher

Tsinghua University Press

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