Limits...
Potent tumor targeting drug release system comprising MMP-2 specific peptide fragment with self-assembling characteristics.

Hua D, Kong W, Zheng X, Zhou Z, Yu B, Li Y, Wang Y, Yang X, Liu C, Tang L, Li Y, Gong M - Drug Des Devel Ther (2014)

Bottom Line: These complexes are beneficial for improving the pharmacological properties and pharmacokinetics of cytotoxic agents, such as doxorubicin and paclitaxel.In the present study, this self-assembling feature was successfully integrated into a hexapeptide with matrix metalloproteinase (MMP)-2 specific targeting activity, producing a supramolecule possessing controlled drug release characteristics.In addition, residence time of the complex in blood was prolonged since paclitaxel was wrapped into the supramolecule.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Tianjin Medical University, Tianjin, People's Republic of China.

ABSTRACT
Self-assembling peptides are capable of forming a complex containing a cavity where cytotoxic agents can be wrapped in a self-assembling manner. These complexes are beneficial for improving the pharmacological properties and pharmacokinetics of cytotoxic agents, such as doxorubicin and paclitaxel. In the present study, this self-assembling feature was successfully integrated into a hexapeptide with matrix metalloproteinase (MMP)-2 specific targeting activity, producing a supramolecule possessing controlled drug release characteristics. The MMP-2 specific substrate fragment, PVGLIG, makes this supramolecule disassociate in the presence of MMP-2, and this system is considered to be a powerful tool for the treatment of tumors with high expression of MMP-2 or tumor metastasis. Our findings show that this modified self-assembling peptide with the PVGLIG fragment was able to significantly enhance specificity against HT1080 cells, a tumor cell line with high expression of MMP-2. In addition, residence time of the complex in blood was prolonged since paclitaxel was wrapped into the supramolecule. Our results suggest that the modified MMP-2 specific substrate, SAMTA7, could act as a controlled and sustained drug carrier for treatment of tumors with high expression of MMP-2 and for tumor metastasis.

Show MeSH

Related in: MedlinePlus

Effect of the SAMTA7-paclitaxel complex on human xenograft tumor model mice bearing (A) HT1080 cells, (B) HEp2 cells, and (C) U-87MG cells. (D) Antitumor effect of the SAMTA7-paclitaxel complex in tumor-bearing mice.Notes: Mice bearing HT1080, HEp2, and U-87MG xenografts were treated with the supramolecule and with free paclitaxel. The antitumor efficacy of the SAMTA7-paclitaxel supramolecule was measured by monitoring the tumor volume after treatment of tumor-bearing mice. Survival time was recorded in days after tumor injection. All data obtained for repeated experiments were pooled and used for the statistical analysis. The results indicate that tumor size decreased more in mice treated with the SAMTA7-paclitaxel complex than in HT1080-bearing mice treated with free paclitaxel. However, the supramolecule exhibited poor antitumor activity in mice bearing HEp2 and U-87MG tumors. In addition, the group treated with the SAMTA7/paclitaxel complex (•) exhibited efficient antitumor activity as shown. Experimental animals showed an improved survival time compared with those treated with free paclitaxel (□; P<0.05, n=10).Abbreviation: PBS, phosphate-buffered saline.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4206202&req=5

f4-dddt-8-1839: Effect of the SAMTA7-paclitaxel complex on human xenograft tumor model mice bearing (A) HT1080 cells, (B) HEp2 cells, and (C) U-87MG cells. (D) Antitumor effect of the SAMTA7-paclitaxel complex in tumor-bearing mice.Notes: Mice bearing HT1080, HEp2, and U-87MG xenografts were treated with the supramolecule and with free paclitaxel. The antitumor efficacy of the SAMTA7-paclitaxel supramolecule was measured by monitoring the tumor volume after treatment of tumor-bearing mice. Survival time was recorded in days after tumor injection. All data obtained for repeated experiments were pooled and used for the statistical analysis. The results indicate that tumor size decreased more in mice treated with the SAMTA7-paclitaxel complex than in HT1080-bearing mice treated with free paclitaxel. However, the supramolecule exhibited poor antitumor activity in mice bearing HEp2 and U-87MG tumors. In addition, the group treated with the SAMTA7/paclitaxel complex (•) exhibited efficient antitumor activity as shown. Experimental animals showed an improved survival time compared with those treated with free paclitaxel (□; P<0.05, n=10).Abbreviation: PBS, phosphate-buffered saline.

Mentions: In order to study the effect of the SAMTA7-paclitaxel supramolecule, mice bearing HT1080, HEp2, or U-87MG xenografts were treated with the supramolecule and free paclitaxel, respectively. The antitumor activity of the SAM-TA7-paclitaxel supramolecule was determined by monitoring tumor volume after treatment in HT1080 tumor-bearing mice (see Figure 4). The supramolecule containing paclitaxel was administered at a paclitaxel dose of 3 mg/kg body weight for 35 days. The free paclitaxel was given at an identical dose and frequency as the control. Figure 4A shows the reduction in tumor size in the mice bearing HT1080 cells and the results revealed that the tumor size was remarkably reduced compared to that of free paclitaxel. However, the supramolecule had poor antitumor activity in mice bearing HEp2 and U-87MG tumors, as shown in Figure 4B and C.


Potent tumor targeting drug release system comprising MMP-2 specific peptide fragment with self-assembling characteristics.

Hua D, Kong W, Zheng X, Zhou Z, Yu B, Li Y, Wang Y, Yang X, Liu C, Tang L, Li Y, Gong M - Drug Des Devel Ther (2014)

Effect of the SAMTA7-paclitaxel complex on human xenograft tumor model mice bearing (A) HT1080 cells, (B) HEp2 cells, and (C) U-87MG cells. (D) Antitumor effect of the SAMTA7-paclitaxel complex in tumor-bearing mice.Notes: Mice bearing HT1080, HEp2, and U-87MG xenografts were treated with the supramolecule and with free paclitaxel. The antitumor efficacy of the SAMTA7-paclitaxel supramolecule was measured by monitoring the tumor volume after treatment of tumor-bearing mice. Survival time was recorded in days after tumor injection. All data obtained for repeated experiments were pooled and used for the statistical analysis. The results indicate that tumor size decreased more in mice treated with the SAMTA7-paclitaxel complex than in HT1080-bearing mice treated with free paclitaxel. However, the supramolecule exhibited poor antitumor activity in mice bearing HEp2 and U-87MG tumors. In addition, the group treated with the SAMTA7/paclitaxel complex (•) exhibited efficient antitumor activity as shown. Experimental animals showed an improved survival time compared with those treated with free paclitaxel (□; P<0.05, n=10).Abbreviation: PBS, phosphate-buffered saline.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4206202&req=5

f4-dddt-8-1839: Effect of the SAMTA7-paclitaxel complex on human xenograft tumor model mice bearing (A) HT1080 cells, (B) HEp2 cells, and (C) U-87MG cells. (D) Antitumor effect of the SAMTA7-paclitaxel complex in tumor-bearing mice.Notes: Mice bearing HT1080, HEp2, and U-87MG xenografts were treated with the supramolecule and with free paclitaxel. The antitumor efficacy of the SAMTA7-paclitaxel supramolecule was measured by monitoring the tumor volume after treatment of tumor-bearing mice. Survival time was recorded in days after tumor injection. All data obtained for repeated experiments were pooled and used for the statistical analysis. The results indicate that tumor size decreased more in mice treated with the SAMTA7-paclitaxel complex than in HT1080-bearing mice treated with free paclitaxel. However, the supramolecule exhibited poor antitumor activity in mice bearing HEp2 and U-87MG tumors. In addition, the group treated with the SAMTA7/paclitaxel complex (•) exhibited efficient antitumor activity as shown. Experimental animals showed an improved survival time compared with those treated with free paclitaxel (□; P<0.05, n=10).Abbreviation: PBS, phosphate-buffered saline.
Mentions: In order to study the effect of the SAMTA7-paclitaxel supramolecule, mice bearing HT1080, HEp2, or U-87MG xenografts were treated with the supramolecule and free paclitaxel, respectively. The antitumor activity of the SAM-TA7-paclitaxel supramolecule was determined by monitoring tumor volume after treatment in HT1080 tumor-bearing mice (see Figure 4). The supramolecule containing paclitaxel was administered at a paclitaxel dose of 3 mg/kg body weight for 35 days. The free paclitaxel was given at an identical dose and frequency as the control. Figure 4A shows the reduction in tumor size in the mice bearing HT1080 cells and the results revealed that the tumor size was remarkably reduced compared to that of free paclitaxel. However, the supramolecule had poor antitumor activity in mice bearing HEp2 and U-87MG tumors, as shown in Figure 4B and C.

Bottom Line: These complexes are beneficial for improving the pharmacological properties and pharmacokinetics of cytotoxic agents, such as doxorubicin and paclitaxel.In the present study, this self-assembling feature was successfully integrated into a hexapeptide with matrix metalloproteinase (MMP)-2 specific targeting activity, producing a supramolecule possessing controlled drug release characteristics.In addition, residence time of the complex in blood was prolonged since paclitaxel was wrapped into the supramolecule.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Tianjin Medical University, Tianjin, People's Republic of China.

ABSTRACT
Self-assembling peptides are capable of forming a complex containing a cavity where cytotoxic agents can be wrapped in a self-assembling manner. These complexes are beneficial for improving the pharmacological properties and pharmacokinetics of cytotoxic agents, such as doxorubicin and paclitaxel. In the present study, this self-assembling feature was successfully integrated into a hexapeptide with matrix metalloproteinase (MMP)-2 specific targeting activity, producing a supramolecule possessing controlled drug release characteristics. The MMP-2 specific substrate fragment, PVGLIG, makes this supramolecule disassociate in the presence of MMP-2, and this system is considered to be a powerful tool for the treatment of tumors with high expression of MMP-2 or tumor metastasis. Our findings show that this modified self-assembling peptide with the PVGLIG fragment was able to significantly enhance specificity against HT1080 cells, a tumor cell line with high expression of MMP-2. In addition, residence time of the complex in blood was prolonged since paclitaxel was wrapped into the supramolecule. Our results suggest that the modified MMP-2 specific substrate, SAMTA7, could act as a controlled and sustained drug carrier for treatment of tumors with high expression of MMP-2 and for tumor metastasis.

Show MeSH
Related in: MedlinePlus