A Novel Gd-DTPA-conjugated Poly(L-γ-glutamyl-glutamine)-paclitaxel Polymeric Delivery System for Tumor Theranostics.

Abstract

The conventional chemotherapeutics could not be traced in vivo and provide timely feedback on the clinical effectiveness of drugs. In this study, poly(L-γ-glutamyl-glutamine)-paclitaxel (PGG-PTX), as a model polymer, was chemically conjugated with Gd-DTPA (Gd-diethylenetriaminepentaacetic acid), a T1-contrast agent of MRI, to prepare a Gd-DTPA-conjugated PGG-PTX (PGG-PTX-DTPA-Gd) delivery system used for tumor theranostics. PGG-PTX-DTPA-Gd can be self-assembled to NPs in water with a z-average hydrodynamic diameter about 35.9 nm. The 3 T MRI results confirmed that the relaxivity of PGG-PTX-DTPA-Gd NPs (r1 = 18.98 mM-1S-1) was increased nearly 4.9 times compared with that of free Gd-DTPA (r1 = 3.87 mM-1S-1). The in vivo fluorescence imaging results showed that PGG-PTX-DTPA-Gd NPs could be accumulated in the tumor tissue of NCI-H460 lung cancer animal model by EPR effect, which was similar to PGG-PTX NPs. The MRI results showed that compared with free Gd-DTPA, PGG-PTX-DTPA-Gd NPs showed significantly enhanced and prolonged signal intensity in tumor tissue, which should be attributed to the increased relaxivity and tumor accumulation. PGG-PTX-DTPA-Gd NPs also showed effective antitumor effect in vivo. These results indicated that PGG-PTX-DTPA-Gd NPs are an effective delivery system for tumor theranostics, and should have a potential value in personalized treatment of tumor.

• Authors: Lipeng Gao, Jinge Zhou, Jing Yu, Qilong Li, Xueying Liu, Lei Sun, Ting Peng, Jing Wang, Jianzhong Zhu, Jihong Sun, Weiyue Lu, Lei Yu, Zhiqiang Yan, Yiting Wang
• Journal: Scientific reports (Sci Rep) Vol. 7 Issue 1 Pg. 3799 (06 19 2017) ISSN: 2045-2322 [Electronic] England
• PMID: 28630436 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Polyglutamic Acid
• Pentetic Acid
• Gadolinium
• Paclitaxel
• paclitaxel poliglumex

Topics

• Animals
• Cell Line, Tumor
• Drug Delivery Systems (methods)
• Gadolinium (chemistry, pharmacology)
• Humans
• Lung Neoplasms (drug therapy, metabolism, pathology)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Paclitaxel (analogs & derivatives, chemistry, pharmacology)
• Pentetic Acid (chemistry, pharmacology)
• Polyglutamic Acid (analogs & derivatives, chemistry, pharmacology)
• Theranostic Nanomedicine (methods)
• Xenograft Model Antitumor Assays