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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

Structure of DOX with two conjugation sites of 13-C carboxyl and 3′-C amino groups.Abbreviation: DOX, doxorubicin.
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f8-ijn-10-101: Structure of DOX with two conjugation sites of 13-C carboxyl and 3′-C amino groups.Abbreviation: DOX, doxorubicin.

Mentions: Even though DOX is one of the highly effective anticancer drugs in chemotherapy, its clinical usage was still limited because of their adverse effects. For safer DOX delivery, biocompatible drug carriers with various drug conjugation techniques have been designed, reducing damage to the normal tissues and organs. As it possesses two conjugatable sites on 13-C carbonyl and 3′-C amino positions (Figure 8), DOX can be conjugated with several cross-linkers by forming a hydrazone bond and an amide bond, respectively. A hydrazone bond, cleavable under a mild acidic condition and stable in neutral pH, enables acid-triggered DOX release in a lysosomal or cancerous environment. Using this bond, DOX molecules were conjugated to diverse novel drug carriers with moderate antitumor efficacy.21,22 On the other hand, DOX could be conjugated with an amide bond at a 3′-C position for the preparation of enzymatically cleavable prodrugs.23,24 In this article, we prepared the DOX–linker–Fbg microspheres with different linkers to evaluate their feasibility as a novel cancer drug delivery system.


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

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

Structure of DOX with two conjugation sites of 13-C carboxyl and 3′-C amino groups.Abbreviation: DOX, doxorubicin.
© Copyright Policy
Related In: Results  -  Collection

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

f8-ijn-10-101: Structure of DOX with two conjugation sites of 13-C carboxyl and 3′-C amino groups.Abbreviation: DOX, doxorubicin.
Mentions: Even though DOX is one of the highly effective anticancer drugs in chemotherapy, its clinical usage was still limited because of their adverse effects. For safer DOX delivery, biocompatible drug carriers with various drug conjugation techniques have been designed, reducing damage to the normal tissues and organs. As it possesses two conjugatable sites on 13-C carbonyl and 3′-C amino positions (Figure 8), DOX can be conjugated with several cross-linkers by forming a hydrazone bond and an amide bond, respectively. A hydrazone bond, cleavable under a mild acidic condition and stable in neutral pH, enables acid-triggered DOX release in a lysosomal or cancerous environment. Using this bond, DOX molecules were conjugated to diverse novel drug carriers with moderate antitumor efficacy.21,22 On the other hand, DOX could be conjugated with an amide bond at a 3′-C position for the preparation of enzymatically cleavable prodrugs.23,24 In this article, we prepared the DOX–linker–Fbg microspheres with different linkers to evaluate their feasibility as a novel cancer drug delivery system.

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