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Drug Design, Development and Therapy Volume 10, 2016 - Issue
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Original Research

Nanomedical strategy to prolong survival period, heighten cure rate, and lower systemic toxicity of S180 mice treated with MTX/MIT

Ning Song1 Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences of Capital Medical University, Beijing, People’s Republic of China
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Ming Zhao1 Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences of Capital Medical University, Beijing, People’s Republic of China;2 Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, TaiwanCorrespondence[email protected] [email protected]
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Yuji Wang1 Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences of Capital Medical University, Beijing, People’s Republic of China
,
Xi Hu1 Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences of Capital Medical University, Beijing, People’s Republic of China
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Jianhui Wu1 Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences of Capital Medical University, Beijing, People’s Republic of China
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Xueyun Jiang1 Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences of Capital Medical University, Beijing, People’s Republic of China
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Shan Li1 Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences of Capital Medical University, Beijing, People’s Republic of China
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Chunying Cui1 Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences of Capital Medical University, Beijing, People’s Republic of China
&
Shiqi Peng1 Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences of Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence[email protected] [email protected]
 show all
Pages 2701-2711 | Published online: 30 Aug 2016

Figures & data

Figure 1 Preparation of MSNN−MTX/MIT.

Notes: The blue particle represents NH2 groups. The red particle represents MIT.
Abbreviations: MSN, mesoporous silica nanoparticles; MSNN, NH2-modified MSN; MTX, methotrexate; MIT, mitoxantrone; TEOS, tetraethyl orthosilicate; APTMS, 3-trimethoxysilyl-propane-1-amine on MSNN.
Figure 1 Preparation of MSNN−MTX/MIT.

Figure 2 Survival of S180 mice treated with CMCNa, MTX/MIT, and MSNN−MTX/MIT during the 7-day administration and the 13-day observation period.

Abbreviations: CMCNa, sodium carboxyl methyl cellulose; MTX, methotrexate; MIT, mitoxantrone; MSNN, amino group-modified mesoporous silica nanoparticles.
Figure 2 Survival of S180 mice treated with CMCNa, MTX/MIT, and MSNN−MTX/MIT during the 7-day administration and the 13-day observation period.

Table 1 Body weight and ratios of organ weight/body weight of MSNN−MTX/MIT- and MTX/MIT-treated S180 mice

Figure 3 Tumor volume of S180 mice treated with CMCNa, MTX/MIT, and MSNN−MTX/MIT.

Note: n=12.
Abbreviations: CMCNa, sodium carboxyl methyl cellulose; MTX, methotrexate; MIT, mitoxantrone; MSNN, amino group-modified mesoporous silica nanoparticles.
Figure 3 Tumor volume of S180 mice treated with CMCNa, MTX/MIT, and MSNN−MTX/MIT.

Figure 4 Tumor weights of CMCNa- and MSNN−MTX/MIT-treated mice.

Note: n=12.
Abbreviations: CMCNa, sodium carboxyl methyl cellulose; MTX, methotrexate; MIT, mitoxantrone; MSNN, amino group-modified mesoporous silica nanoparticles.
Figure 4 Tumor weights of CMCNa- and MSNN−MTX/MIT-treated mice.

Figure 5 Serum ALT, AST, and Cr levels of the mice treated with CMCNa, MTX/MIT, and MSNN−MTX/MIT.

Abbreviations: ALT, alanine transaminase; AST, aspartate transaminase; Cr, creatinine; CMCNa, sodium carboxyl methyl cellulose; MTX, methotrexate; MIT, mitoxantrone; MSNN, amino group-modified mesoporous silica nanoparticles; GOT, glutamic oxaloacetic transaminase; GPT, glutamic pyruvic transaminase.
Figure 5 Serum ALT, AST, and Cr levels of the mice treated with CMCNa, MTX/MIT, and MSNN−MTX/MIT.

Figure 6 α-Chymotrypsin induces the cumulative release profile of MTX from (A) MSNN−MTX and (B) MSNN−MTX/MIT in pH 5.4 PBS.

Abbreviations: MTX, methotrexate; MIT, mitoxantrone; MSNN, amino group-modified mesoporous silica nanoparticles; PBS, phosphate-buffered solution.
Figure 6 α-Chymotrypsin induces the cumulative release profile of MTX from (A) MSNN−MTX and (B) MSNN−MTX/MIT in pH 5.4 PBS.

Figure 7 MSNN−MTX/MIT releases MIT in a time- and pH-dependent manner.

Abbreviations: MTX, methotrexate; MIT, mitoxantrone; MSNN, amino group-modified mesoporous silica nanoparticles.
Figure 7 MSNN−MTX/MIT releases MIT in a time- and pH-dependent manner.

Figure 8 TEM images and ζ potentials.

Notes: (A) MSN, (B) MSNN−MTX, (C) MSNN−MTX/MIT, and (D) SEM image of MSNN−MTX/MIT. Scale bar is 50 nm.
Abbreviations: TEM, transmission electron microscopy; MTX, methotrexate; MIT, mitoxantrone; MSN, mesoporous silica nanoparticle; MSNN, amino group-modified MSN; SEM, scanning electron microscopy.
Figure 8 TEM images and ζ potentials.

Figure 9 IR spectra of MSN, MSNN, MTX, MIT, MSNN−MTX/MIT, and MSNN−MTX.

Abbreviations: IR, infrared; MTX, methotrexate; MIT, mitoxantrone; MSN, mesoporous silica nanoparticle; MSNN, amino group-modified MSN.
Figure 9 IR spectra of MSN, MSNN, MTX, MIT, MSNN−MTX/MIT, and MSNN−MTX.

Figure 10 DSC spectra of MSNN, MIT, MTX, MSNN+MTX, MSNN+MIT, MSNN−MTX, and MSNN−MTX/MIT.

Abbreviations: DSC, differential scanning calorimeter; MTX, methotrexate; MIT, mitoxantrone; MSNN, amino group-modified mesoporous silica nanoparticles.
Figure 10 DSC spectra of MSNN, MIT, MTX, MSNN+MTX, MSNN+MIT, MSNN−MTX, and MSNN−MTX/MIT.

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