Effect of multiple cyclic RGD peptides on tumor accumulation and intratumoral distribution of IRDye 700DX-conjugated polymers.

Abstract:

:Strategic delivery of IRDye 700DX (photosensitizer) is a key for improving its effect in photodynamic therapy. In this study, we have synthesized IRDye 700DX-conjugated polymers containing multiple cyclic RGD peptides to deliver IRDye 700DX selectively to tumor cells and tumor-associated blood vessels overexpressing αvβ3 integrin. Our polymer has a backbone of hydrophilic poly(ethylene glycol)-poly(L-glutamic acid) block copolymer, and cyclic RGD peptides are conjugated to side chains of the poly(L-glutamic acid) while IRDye 700DX is conjugated to the terminal of poly(ethylene glycol). The polymers exhibited selective accumulation to the target sites in a subcutaneous solid tumor, and the accumulation was augmented with the increased number of cyclic RGD peptides. More importantly, the polymer containing 15 cyclic RGD peptides in one construct revealed preferential accumulation on the tumor-associated blood vessels without compromising penetration to deep portions of the tumor, thereby drastically inhibiting tumor growth upon photoirradiation, while the polymer containing 5 cyclic RGD peptides showed moderate antitumor activity despite efficient accumulation in the tumor with almost homogenous intratumoral distribution. These results suggest that controlling the intratumoral distribution of IRDye 700DX is critical for successful PDT, and our polymer containing multiple cyclic RGD peptides may be a promising carrier for this spatial control.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Dou X,Nomoto T,Takemoto H,Matsui M,Tomoda K,Nishiyama N

doi

10.1038/s41598-018-26593-0

subject

Has Abstract

pub_date

2018-05-25 00:00:00

pages

8126

issue

1

issn

2045-2322

pii

10.1038/s41598-018-26593-0

journal_volume

8

pub_type

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