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Original Research

Codelivery of doxorubicin and MDR1-siRNA by mesoporous silica nanoparticles-polymerpolyethylenimine to improve oral squamous carcinoma treatment

Dandan Wang1 Department of Pathology, School and Hospital of Stomatology, Jilin University, Changchun, People’s Republic of China;

Xiaowei Xu2 Department of Periodontology, School and Hospital of Stomatology, Jilin University, Changchun, People’s Republic of China;

Kai Zhang3 State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, People’s Republic of China;

Bin Sun4 Department of Oral and Maxilloficial Syrgery, School and Hospital of Stomatology, Jilin University, Changchun, People’s Republic of China;

Lu Wang1 Department of Pathology, School and Hospital of Stomatology, Jilin University, Changchun, People’s Republic of China;

Lin Meng1 Department of Pathology, School and Hospital of Stomatology, Jilin University, Changchun, People’s Republic of China;

Qilin Liu4 Department of Oral and Maxilloficial Syrgery, School and Hospital of Stomatology, Jilin University, Changchun, People’s Republic of China;

Changyu Zheng5 Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA;

Bai Yang3 State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, People’s Republic of China;

Hongchen Sun1 Department of Pathology, School and Hospital of Stomatology, Jilin University, Changchun, People’s Republic of China;;3 State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, People’s Republic of China;;6 Key Laboratory of Science and Technology for Stomatology Nanoengineering, The Education Department of Jilin Province, Changchun, People’s Republic of ChinaCorrespondence[email protected]

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Table 1 Particle size and zeta potential

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Figure 1 Characteristics of the MSNP and MSNP-PEI nanoparticles.

Notes: (A and B) TEM images of MSNP. (C and D) TEM images of MSNP-PEI. (E) Cell viability assays. (F) Loading ability of MSNP and MSNP-PEI for DOX. (G) Release profile of DOX from MSNP-PEI. (H) Agarose gel electrophoresis retardation assay for MSNP-PEI/pACCMV-EGFP.

Abbreviations: DOX, doxorubicin; MSNP, mesoporous silica nanoparticles; PEI, polymerpolyethylenimine; TEM, transmission electron microscopy.

Figure 2 Transfection efficiency and biological effects of MSNP-PEI-DOX/MDR-siRNA.

Notes: (A–D) Transfection efficiency assay of MSNP-PEI-DOX/MDR1-siRNA^FAM 48 hours posttransfection. (E) Gene expression of MDR1 48 hours posttransfection. (F) Gene expression of MDR1 72 hours posttransfection. * P<0.05, *** P<0.001. (G) KBV cell apoptosis assays 48 hours posttransfection. All results shown are mean value ± SEM (n=3/group).

Abbreviations: DOX, doxorubicin; MDR, multidrug resistance; MSNP, mesoporous silica nanoparticles; NC, negative control; PEI, polymerpolyethylenimine; SEM, standard error of the mean; siRNA, small interfering RNA.

Figure 2 Transfection efficiency and biological effects of MSNP-PEI-DOX/MDR-siRNA.Notes: (A–D) Transfection efficiency assay of MSNP-PEI-DOX/MDR1-siRNAFAM 48 hours posttransfection. (E) Gene expression of MDR1 48 hours posttransfection. (F) Gene expression of MDR1 72 hours posttransfection. * P<0.05, *** P<0.001. (G) KBV cell apoptosis assays 48 hours posttransfection. All results shown are mean value ± SEM (n=3/group).Abbreviations: DOX, doxorubicin; MDR, multidrug resistance; MSNP, mesoporous silica nanoparticles; NC, negative control; PEI, polymerpolyethylenimine; SEM, standard error of the mean; siRNA, small interfering RNA.

Figure 3 Tumor size measurements: photographs of typical mouse bearing tumor and removed KBV tumor xenografts.

Notes: (A and E) Control group. (B and F) MSNP-PEI/siRNA group. (C and G) MSNP-PEI-DOX group. (D and H) MSNP-PEI-DOX/siRNA group. (I) Time course of tumor size measurements. (J) Tumor weights of KBV xenografts at 28 days posttreatment. * P<0.05, ** P<0.01. All results shown are mean value ± SEM (n=5/group). Abbreviations: DOX, doxorubicin; MSNP, mesoporous silica nanoparticles; PEI, polymerpolyethylenimine; SEM, standard error of the mean.

Figure 4 Morphologies of KBV tumor by H&E staining.

Notes: (A) Control; ×200. (B) MSNP-PEI/MDR1-siRNA; ×200. (C) MSNP-PEI-DOX; ×200. (D) MSNP-PEI-DOX/MDR1-siRNA; ×200. The black arrows indicate dead cells resulting in the formation of a uniform pink area.

Abbreviations: DOX, doxorubicin; H&E, hematoxylin and eosin; MDR, multidrug resistance; MSNP, mesoporous silica nanoparticles; PEI, polymerpolyethylenimine.

Figure 4 Morphologies of KBV tumor by H&E staining.Notes: (A) Control; ×200. (B) MSNP-PEI/MDR1-siRNA; ×200. (C) MSNP-PEI-DOX; ×200. (D) MSNP-PEI-DOX/MDR1-siRNA; ×200. The black arrows indicate dead cells resulting in the formation of a uniform pink area.Abbreviations: DOX, doxorubicin; H&E, hematoxylin and eosin; MDR, multidrug resistance; MSNP, mesoporous silica nanoparticles; PEI, polymerpolyethylenimine.

Figure 5 H&E staining of heart, liver, spleen, lung, and kidney; ×200.

Abbreviations: DOX, doxorubicin; H&E, hematoxylin and eosin; MDR, multidrug resistance; MSNP, mesoporous silica nanoparticles; PEI, polymerpolyethylenimine.

Figure 6 Immunohistochemical staining of MDR1, Bcl-2, and Ki67; ×200.

Abbreviations: DOX, doxorubicin; MDR, multidrug resistance; MSNP, mesoporous silica nanoparticles; PEI, polymerpolyethylenimine.

Codelivery of doxorubicin and MDR1-siRNA by mesoporous silica nanoparticles-polymerpolyethylenimine to improve oral squamous carcinoma treatment

Table 1 Particle size and zeta potential

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Codelivery of doxorubicin and MDR1-siRNA by mesoporous silica nanoparticles-polymerpolyethylenimine to improve oral squamous carcinoma treatment

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Table 1 Particle size and zeta potential

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