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Near-Infrared Activatable Phthalocyanine–Poly-L-Glutamic Acid Conjugate: Enhanced in Vivo Safety and Antitumor Efficacy toward an Effective Photodynamic Cancer Therapy
- Source :
- Molecular Pharmaceutics; June 2018, Vol. 15 Issue: 7 p2594-2605, 12p
- Publication Year :
- 2018
-
Abstract
- We previously developed a new zinc(II) phthalocyanine (ZnPc) derivative (Pc 1) conjugated to poly-L-glutamic acid (PGA) (1-PG) to address the limitations of ZnPc as part of an antitumor photodynamic therapy approach, which include hydrophobicity, phototoxicity, and nonselectivity in biodistribution and tumor targeting. During this study, we discovered that 1-PGpossessed high near-infrared (NIR) light absorptivity (λmax= 675 nm), good singlet oxygen generation efficiency in an aqueous environment, and enhanced photocytotoxic efficacy and cancer cell uptake in vitro. In the current study, we discovered that 1-PGaccumulated in 4T1 mouse mammary tumors, with a retention time of up to 48 h. Furthermore, as part of an antitumor PDT, low dose 1-PG(2 mg of Pc 1equivalent/kg) induced a greater tumor volume reduction (−74 ± 5%) when compared to high dose ZnPc(8 mg/kg, −50 ± 12%). At higher treatment doses (8 mg of Pc 1equivalent/kg), 1-PGreduced tumor volume maximally (−91 ± 6%) and suppressed tumor size to a minimal level for up to 15 days. The kidney, liver, and lungs of the mice treated with 1-PG(both low and high doses) were free from 4T1 tumor metastasis at the end of the study. Telemetry-spectral-echocardiography studies also revealed that PGA (65 mg/kg) produced insignificant changes to the cardiovascular physiology of Wistar-Kyoto rats when administered in vivo. Results indicate that PGA displays an excellent cardiovascular safety profile, underlining its suitability for application as a nanodrug carrier in vivo. These current findings indicate the potential of 1-PGas a useful photosensitizer candidate for clinical PDT.
Details
- Language :
- English
- ISSN :
- 15438384 and 15438392
- Volume :
- 15
- Issue :
- 7
- Database :
- Supplemental Index
- Journal :
- Molecular Pharmaceutics
- Publication Type :
- Periodical
- Accession number :
- ejs45612133
- Full Text :
- https://doi.org/10.1021/acs.molpharmaceut.8b00132