Multifunctional Peptide-Amphiphile End-Capped Mesoporous Silica Nanoparticles for Tumor Targeting Drug Delivery
A tumor targeting redox-responsive drug delivery system (DDS) with bioactive surface was constructed by immobilizing peptide-based amphiphile C12-CGRKKRRQRRRPPQRGDS (defined as ADDA-TCPP) onto the mesoporous silica nanoparticles (MSNs) as an end-capping nanovalve, which consists of two main segm...
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| Published in | ACS applied materials & interfaces Vol. 9; no. 3; pp. 2093 - 2103 |
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| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
American Chemical Society
25.01.2017
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| Subjects | |
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| Abstract | A tumor targeting redox-responsive drug delivery system (DDS) with bioactive surface was constructed by immobilizing peptide-based amphiphile C12-CGRKKRRQRRRPPQRGDS (defined as ADDA-TCPP) onto the mesoporous silica nanoparticles (MSNs) as an end-capping nanovalve, which consists of two main segments: a hydrophobic alkyl chain ADDA and a hydrophilic amino acid sequence containing a Tat48‑60 peptide sequence with a thiol terminal group and an RGDS targeting ligand, via a disulfide linkage for redox-triggered intracellular drug delivery. A series of characterizations confirmed that the nanosystem had been successfully fabricated. The antitumor drug doxorubicin (DOX) was selected as a model drug and efficiently trapped in the pores of MSNs, and an in vitro release experiment demonstrated that the mesopores of the resulting DOX-loaded MSNs (DOX@MSN-ss-ADDA-TCPP) could be sealed tightly with ADDA-TCPP self-assemblies through hydrophobic interactions between the alkyl chains; the resulting DDS exhibited “zero premature release” of DOX in the physical environment. However, a burst drug release was triggered by a high concentration of glutathione (GSH) in simulated cellular cytosol. Moreover, detailed investigations confirmed that incorporation of RGDS peptide facilitated the active targeting delivery of DOX to αvβ3 integrin overexpressed tumor cells, and Tat48‑60 modification on MSNs could enhance intracellular drug delivery, exhibiting an obvious toxicity to tumor cells. The multifunctional nanosystem constructed here can realize the controlled drug release and serve as a platform for designing multifunctional nanocarriers using diversified bioactive peptide-based amphiphile. |
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| AbstractList | A tumor targeting redox-responsive drug delivery system (DDS) with bioactive surface was constructed by immobilizing peptide-based amphiphile C12-CGRKKRRQRRRPPQRGDS (defined as ADDA-TCPP) onto the mesoporous silica nanoparticles (MSNs) as an end-capping nanovalve, which consists of two main segments: a hydrophobic alkyl chain ADDA and a hydrophilic amino acid sequence containing a Tat48-60 peptide sequence with a thiol terminal group and an RGDS targeting ligand, via a disulfide linkage for redox-triggered intracellular drug delivery. A series of characterizations confirmed that the nanosystem had been successfully fabricated. The antitumor drug doxorubicin (DOX) was selected as a model drug and efficiently trapped in the pores of MSNs, and an in vitro release experiment demonstrated that the mesopores of the resulting DOX-loaded MSNs (DOX@MSN-ss-ADDA-TCPP) could be sealed tightly with ADDA-TCPP self-assemblies through hydrophobic interactions between the alkyl chains; the resulting DDS exhibited "zero premature release" of DOX in the physical environment. However, a burst drug release was triggered by a high concentration of glutathione (GSH) in simulated cellular cytosol. Moreover, detailed investigations confirmed that incorporation of RGDS peptide facilitated the active targeting delivery of DOX to αvβ3 integrin overexpressed tumor cells, and Tat48-60 modification on MSNs could enhance intracellular drug delivery, exhibiting an obvious toxicity to tumor cells. The multifunctional nanosystem constructed here can realize the controlled drug release and serve as a platform for designing multifunctional nanocarriers using diversified bioactive peptide-based amphiphile.A tumor targeting redox-responsive drug delivery system (DDS) with bioactive surface was constructed by immobilizing peptide-based amphiphile C12-CGRKKRRQRRRPPQRGDS (defined as ADDA-TCPP) onto the mesoporous silica nanoparticles (MSNs) as an end-capping nanovalve, which consists of two main segments: a hydrophobic alkyl chain ADDA and a hydrophilic amino acid sequence containing a Tat48-60 peptide sequence with a thiol terminal group and an RGDS targeting ligand, via a disulfide linkage for redox-triggered intracellular drug delivery. A series of characterizations confirmed that the nanosystem had been successfully fabricated. The antitumor drug doxorubicin (DOX) was selected as a model drug and efficiently trapped in the pores of MSNs, and an in vitro release experiment demonstrated that the mesopores of the resulting DOX-loaded MSNs (DOX@MSN-ss-ADDA-TCPP) could be sealed tightly with ADDA-TCPP self-assemblies through hydrophobic interactions between the alkyl chains; the resulting DDS exhibited "zero premature release" of DOX in the physical environment. However, a burst drug release was triggered by a high concentration of glutathione (GSH) in simulated cellular cytosol. Moreover, detailed investigations confirmed that incorporation of RGDS peptide facilitated the active targeting delivery of DOX to αvβ3 integrin overexpressed tumor cells, and Tat48-60 modification on MSNs could enhance intracellular drug delivery, exhibiting an obvious toxicity to tumor cells. The multifunctional nanosystem constructed here can realize the controlled drug release and serve as a platform for designing multifunctional nanocarriers using diversified bioactive peptide-based amphiphile. A tumor targeting redox-responsive drug delivery system (DDS) with bioactive surface was constructed by immobilizing peptide-based amphiphile C12-CGRKKRRQRRRPPQRGDS (defined as ADDA-TCPP) onto the mesoporous silica nanoparticles (MSNs) as an end-capping nanovalve, which consists of two main segments: a hydrophobic alkyl chain ADDA and a hydrophilic amino acid sequence containing a Tat₄₈₋₆₀ peptide sequence with a thiol terminal group and an RGDS targeting ligand, via a disulfide linkage for redox-triggered intracellular drug delivery. A series of characterizations confirmed that the nanosystem had been successfully fabricated. The antitumor drug doxorubicin (DOX) was selected as a model drug and efficiently trapped in the pores of MSNs, and an in vitro release experiment demonstrated that the mesopores of the resulting DOX-loaded MSNs (DOX@MSN-ss-ADDA-TCPP) could be sealed tightly with ADDA-TCPP self-assemblies through hydrophobic interactions between the alkyl chains; the resulting DDS exhibited “zero premature release” of DOX in the physical environment. However, a burst drug release was triggered by a high concentration of glutathione (GSH) in simulated cellular cytosol. Moreover, detailed investigations confirmed that incorporation of RGDS peptide facilitated the active targeting delivery of DOX to αᵥβ₃ integrin overexpressed tumor cells, and Tat₄₈₋₆₀ modification on MSNs could enhance intracellular drug delivery, exhibiting an obvious toxicity to tumor cells. The multifunctional nanosystem constructed here can realize the controlled drug release and serve as a platform for designing multifunctional nanocarriers using diversified bioactive peptide-based amphiphile. A tumor targeting redox-responsive drug delivery system (DDS) with bioactive surface was constructed by immobilizing peptide-based amphiphile C12-CGRKKRRQRRRPPQRGDS (defined as ADDA-TCPP) onto the mesoporous silica nanoparticles (MSNs) as an end-capping nanovalve, which consists of two main segments: a hydrophobic alkyl chain ADDA and a hydrophilic amino acid sequence containing a Tat48‑60 peptide sequence with a thiol terminal group and an RGDS targeting ligand, via a disulfide linkage for redox-triggered intracellular drug delivery. A series of characterizations confirmed that the nanosystem had been successfully fabricated. The antitumor drug doxorubicin (DOX) was selected as a model drug and efficiently trapped in the pores of MSNs, and an in vitro release experiment demonstrated that the mesopores of the resulting DOX-loaded MSNs (DOX@MSN-ss-ADDA-TCPP) could be sealed tightly with ADDA-TCPP self-assemblies through hydrophobic interactions between the alkyl chains; the resulting DDS exhibited “zero premature release” of DOX in the physical environment. However, a burst drug release was triggered by a high concentration of glutathione (GSH) in simulated cellular cytosol. Moreover, detailed investigations confirmed that incorporation of RGDS peptide facilitated the active targeting delivery of DOX to αvβ3 integrin overexpressed tumor cells, and Tat48‑60 modification on MSNs could enhance intracellular drug delivery, exhibiting an obvious toxicity to tumor cells. The multifunctional nanosystem constructed here can realize the controlled drug release and serve as a platform for designing multifunctional nanocarriers using diversified bioactive peptide-based amphiphile. A tumor targeting redox-responsive drug delivery system (DDS) with bioactive surface was constructed by immobilizing peptide-based amphiphile C12-CGRKKRRQRRRPPQRGDS (defined as ADDA-TCPP) onto the mesoporous silica nanoparticles (MSNs) as an end-capping nanovalve, which consists of two main segments: a hydrophobic alkyl chain ADDA and a hydrophilic amino acid sequence containing a Tat peptide sequence with a thiol terminal group and an RGDS targeting ligand, via a disulfide linkage for redox-triggered intracellular drug delivery. A series of characterizations confirmed that the nanosystem had been successfully fabricated. The antitumor drug doxorubicin (DOX) was selected as a model drug and efficiently trapped in the pores of MSNs, and an in vitro release experiment demonstrated that the mesopores of the resulting DOX-loaded MSNs (DOX@MSN-ss-ADDA-TCPP) could be sealed tightly with ADDA-TCPP self-assemblies through hydrophobic interactions between the alkyl chains; the resulting DDS exhibited "zero premature release" of DOX in the physical environment. However, a burst drug release was triggered by a high concentration of glutathione (GSH) in simulated cellular cytosol. Moreover, detailed investigations confirmed that incorporation of RGDS peptide facilitated the active targeting delivery of DOX to α β integrin overexpressed tumor cells, and Tat modification on MSNs could enhance intracellular drug delivery, exhibiting an obvious toxicity to tumor cells. The multifunctional nanosystem constructed here can realize the controlled drug release and serve as a platform for designing multifunctional nanocarriers using diversified bioactive peptide-based amphiphile. |
| Author | Zhang, Ai-Qing He, Feng Hu, Jing-Jing Zeng, Xuan Zhang, Xian-Zheng Cheng, Yin-Jia |
| AuthorAffiliation | Wuhan University School of Chemistry and Materials Science Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry South-Central University for Nationalities |
| AuthorAffiliation_xml | – name: School of Chemistry and Materials Science – name: South-Central University for Nationalities – name: Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry – name: Wuhan University |
| Author_xml | – sequence: 1 givenname: Yin-Jia orcidid: 0000-0001-6445-3138 surname: Cheng fullname: Cheng, Yin-Jia email: ChengYJ@mail.scuec.edu.cn – sequence: 2 givenname: Ai-Qing surname: Zhang fullname: Zhang, Ai-Qing – sequence: 3 givenname: Jing-Jing surname: Hu fullname: Hu, Jing-Jing – sequence: 4 givenname: Feng surname: He fullname: He, Feng – sequence: 5 givenname: Xuan surname: Zeng fullname: Zeng, Xuan email: zeng_xuan@163.com – sequence: 6 givenname: Xian-Zheng orcidid: 0000-0001-6242-6005 surname: Zhang fullname: Zhang, Xian-Zheng |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/28032742$$D View this record in MEDLINE/PubMed |
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| SubjectTerms | amino acid sequences cytosol Doxorubicin Drug Carriers Drug Delivery Systems Drug Liberation glutathione hydrophilicity hydrophobic bonding hydrophobicity integrins ligands nanocarriers Nanoparticles neoplasm cells Peptides Porosity porous media silica Silicon Dioxide thiols toxicity |
| Title | Multifunctional Peptide-Amphiphile End-Capped Mesoporous Silica Nanoparticles for Tumor Targeting Drug Delivery |
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