Arginylglycylaspartic Acid-Surface-Functionalized Doxorubicin-Loaded Lipid-Core Nanocapsules as a Strategy to Target Alpha(V) Beta(3) Integrin Expressed on Tumor Cells
Doxorubicin (Dox) clinical use is limited by dose-related cardiomyopathy, becoming more prevalent with increasing cumulative doses. Previously, we developed Dox-loaded lipid-core nanocapsules (Dox-LNC) and, in this study, we hypothesized that self-assembling and interfacial reactions could be used t...
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| Format: | Article |
| Language: | English |
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MDPI AG
2017-12-01
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| Series: | Nanomaterials |
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| Online Access: | https://www.mdpi.com/2079-4991/8/1/2 |
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| author | Michelli B. Antonow Camila Franco Willian Prado Aline Beckenkamp Gustavo P. Silveira Andréia Buffon Sílvia S. Guterres Adriana R. Pohlmann |
| author_facet | Michelli B. Antonow Camila Franco Willian Prado Aline Beckenkamp Gustavo P. Silveira Andréia Buffon Sílvia S. Guterres Adriana R. Pohlmann |
| author_sort | Michelli B. Antonow |
| collection | DOAJ |
| description | Doxorubicin (Dox) clinical use is limited by dose-related cardiomyopathy, becoming more prevalent with increasing cumulative doses. Previously, we developed Dox-loaded lipid-core nanocapsules (Dox-LNC) and, in this study, we hypothesized that self-assembling and interfacial reactions could be used to obtain arginylglycylaspartic acid (RGD)-surface-functionalized-Dox-LNC, which could target tumoral cells overexpressing αvβ3 integrin. Human breast adenocarcinoma cell line (MCF-7) and human glioblastoma astrocytoma (U87MG) expressing different levels of αvβ3 integrin were studied. RGD-functionalized Dox-LNC were prepared with Dox at 100 and 500 mg·mL−1 (RGD-MCMN (Dox100) and RGD-MCMN (Dox500)). Blank formulation (RGD-MCMN) had z-average diameter of 162 ± 6 nm, polydispersity index of 0.11 ± 0.04, zeta potential of +13.2 ± 1.9 mV and (6.2 ± 1.1) × 1011 particles mL−1, while RGD-MCMN (Dox100) and RGD-MCMN (Dox500) showed respectively 146 ± 20 and 215 ± 25 nm, 0.10 ± 0.01 and 0.09 ± 0.03, +13.8 ± 2.3 and +16.4 ± 1.5 mV and (6.9 ± 0.6) × 1011 and (6.1 ± 1.0) × 1011 particles mL−1. RGD complexation was 7.73 × 104 molecules per nanocapsule and Dox loading were 1.51 × 104 and 7.64 × 104 molecules per nanocapsule, respectively. RGD-functionalized nanocapsules had an improved uptake capacity by U87MG cells. Pareto chart showed that the cell viability was mainly affected by the Dox concentration and the period of treatment in both MCF-7 and U87MG. The influence of RGD-functionalization on cell viability was a determinant factor exclusively to U87MG. |
| first_indexed | 2024-12-21T12:41:58Z |
| format | Article |
| id | doaj.art-9c0accd767d84d40bd06b3c9cc8ecf37 |
| institution | Directory Open Access Journal |
| issn | 2079-4991 |
| language | English |
| last_indexed | 2024-12-21T12:41:58Z |
| publishDate | 2017-12-01 |
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| series | Nanomaterials |
| spelling | doaj.art-9c0accd767d84d40bd06b3c9cc8ecf372022-12-21T19:03:45ZengMDPI AGNanomaterials2079-49912017-12-0181210.3390/nano8010002nano8010002Arginylglycylaspartic Acid-Surface-Functionalized Doxorubicin-Loaded Lipid-Core Nanocapsules as a Strategy to Target Alpha(V) Beta(3) Integrin Expressed on Tumor CellsMichelli B. Antonow0Camila Franco1Willian Prado2Aline Beckenkamp3Gustavo P. Silveira4Andréia Buffon5Sílvia S. Guterres6Adriana R. Pohlmann7Programa de Pós-Graduação em Nanotecnologia Farmacêutica, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga, 2752, Porto Alegre 90610-000 RS, BrazilPrograma de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga, 2752, Porto Alegre 90610-000 RS, BrazilDepartamento de Química Orgânica, Instituto de Química, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves, 9500, Porto Alegre 91501-970 RS, BrazilPrograma de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga, 2752, Porto Alegre 90610-000 RS, BrazilDepartamento de Química Orgânica, Instituto de Química, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves, 9500, Porto Alegre 91501-970 RS, BrazilPrograma de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga, 2752, Porto Alegre 90610-000 RS, BrazilPrograma de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga, 2752, Porto Alegre 90610-000 RS, BrazilPrograma de Pós-Graduação em Nanotecnologia Farmacêutica, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga, 2752, Porto Alegre 90610-000 RS, BrazilDoxorubicin (Dox) clinical use is limited by dose-related cardiomyopathy, becoming more prevalent with increasing cumulative doses. Previously, we developed Dox-loaded lipid-core nanocapsules (Dox-LNC) and, in this study, we hypothesized that self-assembling and interfacial reactions could be used to obtain arginylglycylaspartic acid (RGD)-surface-functionalized-Dox-LNC, which could target tumoral cells overexpressing αvβ3 integrin. Human breast adenocarcinoma cell line (MCF-7) and human glioblastoma astrocytoma (U87MG) expressing different levels of αvβ3 integrin were studied. RGD-functionalized Dox-LNC were prepared with Dox at 100 and 500 mg·mL−1 (RGD-MCMN (Dox100) and RGD-MCMN (Dox500)). Blank formulation (RGD-MCMN) had z-average diameter of 162 ± 6 nm, polydispersity index of 0.11 ± 0.04, zeta potential of +13.2 ± 1.9 mV and (6.2 ± 1.1) × 1011 particles mL−1, while RGD-MCMN (Dox100) and RGD-MCMN (Dox500) showed respectively 146 ± 20 and 215 ± 25 nm, 0.10 ± 0.01 and 0.09 ± 0.03, +13.8 ± 2.3 and +16.4 ± 1.5 mV and (6.9 ± 0.6) × 1011 and (6.1 ± 1.0) × 1011 particles mL−1. RGD complexation was 7.73 × 104 molecules per nanocapsule and Dox loading were 1.51 × 104 and 7.64 × 104 molecules per nanocapsule, respectively. RGD-functionalized nanocapsules had an improved uptake capacity by U87MG cells. Pareto chart showed that the cell viability was mainly affected by the Dox concentration and the period of treatment in both MCF-7 and U87MG. The influence of RGD-functionalization on cell viability was a determinant factor exclusively to U87MG.https://www.mdpi.com/2079-4991/8/1/2lipid-core nanocapsulescancerRGDDoxorubicinactive drug targetingsurface-functionalization |
| spellingShingle | Michelli B. Antonow Camila Franco Willian Prado Aline Beckenkamp Gustavo P. Silveira Andréia Buffon Sílvia S. Guterres Adriana R. Pohlmann Arginylglycylaspartic Acid-Surface-Functionalized Doxorubicin-Loaded Lipid-Core Nanocapsules as a Strategy to Target Alpha(V) Beta(3) Integrin Expressed on Tumor Cells Nanomaterials lipid-core nanocapsules cancer RGD Doxorubicin active drug targeting surface-functionalization |
| title | Arginylglycylaspartic Acid-Surface-Functionalized Doxorubicin-Loaded Lipid-Core Nanocapsules as a Strategy to Target Alpha(V) Beta(3) Integrin Expressed on Tumor Cells |
| title_full | Arginylglycylaspartic Acid-Surface-Functionalized Doxorubicin-Loaded Lipid-Core Nanocapsules as a Strategy to Target Alpha(V) Beta(3) Integrin Expressed on Tumor Cells |
| title_fullStr | Arginylglycylaspartic Acid-Surface-Functionalized Doxorubicin-Loaded Lipid-Core Nanocapsules as a Strategy to Target Alpha(V) Beta(3) Integrin Expressed on Tumor Cells |
| title_full_unstemmed | Arginylglycylaspartic Acid-Surface-Functionalized Doxorubicin-Loaded Lipid-Core Nanocapsules as a Strategy to Target Alpha(V) Beta(3) Integrin Expressed on Tumor Cells |
| title_short | Arginylglycylaspartic Acid-Surface-Functionalized Doxorubicin-Loaded Lipid-Core Nanocapsules as a Strategy to Target Alpha(V) Beta(3) Integrin Expressed on Tumor Cells |
| title_sort | arginylglycylaspartic acid surface functionalized doxorubicin loaded lipid core nanocapsules as a strategy to target alpha v beta 3 integrin expressed on tumor cells |
| topic | lipid-core nanocapsules cancer RGD Doxorubicin active drug targeting surface-functionalization |
| url | https://www.mdpi.com/2079-4991/8/1/2 |
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