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Biocompatible and biodegradable fibrinogen microspheres for tumor-targeted doxorubicin delivery.

Joo JY, Park GY, An SS - Int J Nanomedicine (2015)

Bottom Line: Doxorubicin (DOX), a chemotherapeutic agent, was covalently conjugated to Fbg, and the microspheres were prepared.In vitro cytotoxicity tests confirmed low cytotoxicity in normal cells and high antitumor effect toward cancer cells.Therefore, DOX-linker-Fbg microspheres could be a suitable drug carrier for safer and effective drug delivery.

View Article: PubMed Central - PubMed

Affiliation: Department of Bionano Technology, Gachon Medical Research Institute, Gachon University, Seongnam-si, Republic of Korea.

ABSTRACT
In the development of effective drug delivery carriers, many researchers have focused on the usage of nontoxic and biocompatible materials and surface modification with targeting molecules for tumor-specific drug delivery. Fibrinogen (Fbg), an abundant glycoprotein in plasma, could be a potential candidate for developing drug carriers because of its biocompatibility and tumor-targeting property via arginine-glycine-aspartate (RGD) peptide sequences. Doxorubicin (DOX), a chemotherapeutic agent, was covalently conjugated to Fbg, and the microspheres were prepared. Acid-labile and non-cleavable linkers were used for the conjugation of DOX to Fbg, resulting in an acid-triggered drug release under a mild acidic condition and a slow-controlled drug release, respectively. In vitro cytotoxicity tests confirmed low cytotoxicity in normal cells and high antitumor effect toward cancer cells. In addition, it was discovered that a longer linker could make the binding of cells to Fbg drug carriers easier. Therefore, DOX-linker-Fbg microspheres could be a suitable drug carrier for safer and effective drug delivery.

No MeSH data available.


Related in: MedlinePlus

SEM images of bare, DOX–linker–Fbg microspheres.Notes: (A and B) Bare-Fbg microspheres, (C and D) DOX–(3-MAH)–Fbg microspheres, (E and F) DOX–SM(PEG)12–Fbg microspheres. (A, C, and E) before the degradation, and (B, D, and F) after the degradation.Abbreviations: SEM, scanning electron microscope; DOX, doxorubicin; Fbg, fibrinogen; 3-MAH, 3-maleimidopropionic acid hydrazonium trifluoroacetic acid; SM(PEG)12, succinimidyl-[(N-maleimidopropionamido)-dodecaethylene glycol] ester.
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f4-ijn-10-101: SEM images of bare, DOX–linker–Fbg microspheres.Notes: (A and B) Bare-Fbg microspheres, (C and D) DOX–(3-MAH)–Fbg microspheres, (E and F) DOX–SM(PEG)12–Fbg microspheres. (A, C, and E) before the degradation, and (B, D, and F) after the degradation.Abbreviations: SEM, scanning electron microscope; DOX, doxorubicin; Fbg, fibrinogen; 3-MAH, 3-maleimidopropionic acid hydrazonium trifluoroacetic acid; SM(PEG)12, succinimidyl-[(N-maleimidopropionamido)-dodecaethylene glycol] ester.

Mentions: Outer morphology, surface fine structure, degradation form were observed using a SEM. Spherical and porous Fbg microspheres with approximately 20 µm size were prepared, with a nano-structured surface (Figure 3A–C). Likewise, DOX–linker 1–Fbg microspheres were fabricated with approximately 10 µm diameter and highly porous surface (Figure 3D–F). Degradation of bare-Fbg microspheres was analyzed (Figure 4A and B), degradation of DOX–(3-MAH)–Fbg microspheres was analyzed (Figure 4C and D), and Degradation of DOX–SM(PEG)12–Fbg was analyzed (Figure 4E and F).


Biocompatible and biodegradable fibrinogen microspheres for tumor-targeted doxorubicin delivery.

Joo JY, Park GY, An SS - Int J Nanomedicine (2015)

SEM images of bare, DOX–linker–Fbg microspheres.Notes: (A and B) Bare-Fbg microspheres, (C and D) DOX–(3-MAH)–Fbg microspheres, (E and F) DOX–SM(PEG)12–Fbg microspheres. (A, C, and E) before the degradation, and (B, D, and F) after the degradation.Abbreviations: SEM, scanning electron microscope; DOX, doxorubicin; Fbg, fibrinogen; 3-MAH, 3-maleimidopropionic acid hydrazonium trifluoroacetic acid; SM(PEG)12, succinimidyl-[(N-maleimidopropionamido)-dodecaethylene glycol] ester.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4562758&req=5

f4-ijn-10-101: SEM images of bare, DOX–linker–Fbg microspheres.Notes: (A and B) Bare-Fbg microspheres, (C and D) DOX–(3-MAH)–Fbg microspheres, (E and F) DOX–SM(PEG)12–Fbg microspheres. (A, C, and E) before the degradation, and (B, D, and F) after the degradation.Abbreviations: SEM, scanning electron microscope; DOX, doxorubicin; Fbg, fibrinogen; 3-MAH, 3-maleimidopropionic acid hydrazonium trifluoroacetic acid; SM(PEG)12, succinimidyl-[(N-maleimidopropionamido)-dodecaethylene glycol] ester.
Mentions: Outer morphology, surface fine structure, degradation form were observed using a SEM. Spherical and porous Fbg microspheres with approximately 20 µm size were prepared, with a nano-structured surface (Figure 3A–C). Likewise, DOX–linker 1–Fbg microspheres were fabricated with approximately 10 µm diameter and highly porous surface (Figure 3D–F). Degradation of bare-Fbg microspheres was analyzed (Figure 4A and B), degradation of DOX–(3-MAH)–Fbg microspheres was analyzed (Figure 4C and D), and Degradation of DOX–SM(PEG)12–Fbg was analyzed (Figure 4E and F).

Bottom Line: Doxorubicin (DOX), a chemotherapeutic agent, was covalently conjugated to Fbg, and the microspheres were prepared.In vitro cytotoxicity tests confirmed low cytotoxicity in normal cells and high antitumor effect toward cancer cells.Therefore, DOX-linker-Fbg microspheres could be a suitable drug carrier for safer and effective drug delivery.

View Article: PubMed Central - PubMed

Affiliation: Department of Bionano Technology, Gachon Medical Research Institute, Gachon University, Seongnam-si, Republic of Korea.

ABSTRACT
In the development of effective drug delivery carriers, many researchers have focused on the usage of nontoxic and biocompatible materials and surface modification with targeting molecules for tumor-specific drug delivery. Fibrinogen (Fbg), an abundant glycoprotein in plasma, could be a potential candidate for developing drug carriers because of its biocompatibility and tumor-targeting property via arginine-glycine-aspartate (RGD) peptide sequences. Doxorubicin (DOX), a chemotherapeutic agent, was covalently conjugated to Fbg, and the microspheres were prepared. Acid-labile and non-cleavable linkers were used for the conjugation of DOX to Fbg, resulting in an acid-triggered drug release under a mild acidic condition and a slow-controlled drug release, respectively. In vitro cytotoxicity tests confirmed low cytotoxicity in normal cells and high antitumor effect toward cancer cells. In addition, it was discovered that a longer linker could make the binding of cells to Fbg drug carriers easier. Therefore, DOX-linker-Fbg microspheres could be a suitable drug carrier for safer and effective drug delivery.

No MeSH data available.


Related in: MedlinePlus