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Immunomodulatory and enhanced antitumor activity of a modified thymosin α1 in melanoma and lung cancer
- Source :
- International Journal of Pharmaceutics. 547:611-620
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- Tumor-targeted therapy is an attractive strategy for cancer treatment. Peptide hormone thymosin α1 (Tα1) has been used against several diseases, including cancer, but its activity is pleiotropic. Herein, we designed a fusion protein Tα1-iRGD by introducing the tumor homing peptide iRGD to Tα1. Results show that Tα1-iRGD can promote T-cell activation and CD86 expression, thereby exerting better effect and stronger inhibitory against melanoma and lung cancer, respectively, than Tα1 in vivo. These effects are indicated by the reduced densities of tumor vessels and Tα1-iRGD accumulation in tumors. Moreover, compared with Tα1, Tα1-iRGD can attach more B16F10 and H460 cells and exhibits significantly better immunomodulatory activity in immunosuppression models induced by hydrocortisone. Circular dichroism spectroscopy and structural analysis results revealed that Tα1 and Tα1-iRGD both adopted a helical confirmation in the presence of trifluoroethanol, indicating the structural basis of their functions. These findings highlight the vital function of Tα1-iRGD in tumor-targeted therapy and suggest that Tα1-iRGD is a better antitumor drug than Tα1.
- Subjects :
- 0301 basic medicine
Lung Neoplasms
Thymalfasin
Recombinant Fusion Proteins
T-Lymphocytes
medicine.medical_treatment
Mice, Nude
Pharmaceutical Science
Antineoplastic Agents
Lymphocyte Activation
Protein Structure, Secondary
Mice
03 medical and health sciences
Adjuvants, Immunologic
In vivo
Cell Line, Tumor
Immune Tolerance
medicine
Animals
Humans
Tumor-homing Peptide iRGD
Lung cancer
Melanoma
Cell Proliferation
CD86
Mice, Inbred BALB C
Mice, Inbred ICR
Chemistry
Circular Dichroism
Cancer
Immunosuppression
Trifluoroethanol
medicine.disease
Xenograft Model Antitumor Assays
Fusion protein
Mice, Inbred C57BL
Thymosin
030104 developmental biology
Cancer research
Female
B7-2 Antigen
Oligopeptides
Subjects
Details
- ISSN :
- 03785173
- Volume :
- 547
- Database :
- OpenAIRE
- Journal :
- International Journal of Pharmaceutics
- Accession number :
- edsair.doi.dedup.....e048b3f052f2fb6f5249b1bdc1a53cb2