6-Aminocaproic acid as a linker to improve near-infrared fluorescence imaging and photothermal cancer therapy of PEGylated indocyanine green

Clinical extensive application of indocyanine green (ICG) is limited by several drawbacks such as poor bio-environmental stability, aggregate propensity, and rapid elimination from the body, etc. In this study, we construct a novel amphiphilic mPEG-ACA-ICG conjugate by modifying synthetic heptamethine cyanine derivative ICG-COOH with a hydrophobic linker 6-aminocaproic acid (ACA) and amino-terminal poly(ethylene glycol) (mPEG-NH2). The as-prepared mPEG-ACA-ICG conjugate has the ability to self-assemble into micellar aggregates in an aqueous solution with a lower CMC value than mPEG-ICG conjugate without ACA linker. More importantly, compared with free ICG and mPEG-ICG conjugate, mPEG-ACA-ICG nanomicelles exhibited better stability and higher photothermal conversion efficiency upon near-infrared light irradiation due to the intramolecular introduction of a hydrophobic ACA segment. In our in vivo experiment, mPEG-ACA-ICG nanomicelles ensured the formidable effect on tumor photothermal therapy (PTT) and the maximum tumor inhibition rate reached 72.6 %. In addition, real-time determination ability for fluorescence image-guided surgery (FIGS) of mPEG-ACA-ICG nanomicelles was also confirmed on tumor xenograft mice model. Taken together, mPEG-ACA-ICG conjugate may hold great promise for non-invasive cancer theranostics.

Automated summary

A novel amphiphilic mPEG-ACA-ICG conjugate was successfully constructed by modifying ICG with a hydrophobic linker ACA and mPEG, showing improved stability and photothermal conversion efficiency. The nanomicelles exhibited great potential for tumor photothermal therapy and fluorescence image-guided surgery.