Smart Self‐Assembly Amphiphilic Cyclopeptide‐Dye for Near‐Infrared Window‐II Imaging

Abstract

compared with small molecular drugs. However, Food and Drug Administration (FDA) approval of nanosized agents has been hindered by their often complex and ambiguous chemical formulas. [2] Small molecular self-assembled nanoparticles have the potential to combine the small molecular compounds' simple chemical formulas advantage with the traditional nanoparticles' promising tumor accumulation advantage, which would make the FDA approval easier. However, small-molecule-based nanoprobes with desirable tumor microenvironment response abilities and outstanding in vivo performance are scanty. Although many existing small molecules have "smart" properties that allow them to respond to stimuli such as pH changes, small molecules that are sensitive in narrow physiological pH ranges (≈6.8-7.4) have been difficult to design. Typically, acidic microenvironments are found in solid tumor tissues (pH 6.5-6.8), [1] inflammatory sites, [3] and are associated with bone resorption by osteoclasts (pH < 5.5). [4] A pH-sensitive agent that can respond to the acidic microenvironment of solid tumor tissues (pH 6.5-6.8) [1] would be invaluable for potential theranostics of diseases. Previous sharp pH responsive polymer based nanoparticles (translation at pH 6.7, ΔpH ON/OFF < 0.25) could Development of novel nanomaterials for disease theranostics represents an important direction in chemistry and precision medicine. Fluorescent molecular probes in the second near-infrared window (NIR-II, 1000-1700 nm) show high promise because of their exceptional high detection sensitivity, resolution, and deep imaging depth. Here, a sharp pH-sensitive self-assembling cyclopeptide-dye, SIMM1000, as a smart nanoprobe for NIR-II imaging of diseases in living animals, is reported. This small molecule assembled nanoprobe exhibits smart properties by responding to a sharp decrease of pH in the tumor microenvironment (pH 7.0 to 6.8), aggregating from small nanoprobe (80 nm at pH 7.0) into large nanoparticles (>500 nm at pH 6.8) with ≈20-30 times enhanced fluorescence compared with the non-self-assembled CH-4T. It yields micrometer-scale resolution in blood vessel imaging and high contrast and resolution in bone and tumor imaging in mice. Because of its self-aggregation in acidic tumor microenvironments in situ, SIMM1000 exhibits high tumor accumulation and extremely long tumor retention (>19 days), while being excretable from normal tissues and safe. This smart self-assembling small molecule strategy can shift the paradigm of designing new nanomaterials for molecular imaging and drug development.Development of nanomaterials for molecular imaging and treatment of disease is a highly promising and dynamic field in chemistry and precision medicine. Nanomaterials offer numerous benefits for cancer theranostics development, such as long-circulation time, excellent tumor microenvironment response abilities, and the enhanced permeability and retentionThe ORCID identification number(s) for the author(s) of this article can be found under

Recent Advances in Near‐Infrared‐II Fluorescence Imaging for Deep‐Tissue Molecular Analysis and Cancer Diagnosis

“…Cheng and co‐workers reported a molecule nanoprobe cyclopeptide‐dye, SIMM1000, allowing it to form aggregation morphology under a low‐pH environment ( Figure A). [ 25 ] The nanoprobes showed a small size of 80 nm at pH 7.5, whereas the particle size could be increased to >500 nm upon exposure in the pH 6.8 condition with the enhancement of NIR‐II fluorescence signals via the photoluminescence mechanism of aggregation‐induced emission (AIE), which suggested its sensitive responsibility to the weakly acidic TME (pH 7.0 to 6.8) (Figure 7B). Upon injection into the tumor‐bearing mice, SIMM1000 nanoparticles accumulated first in the tumor region due to RGD‐mediated integrin targeting and recovered the NIR‐II fluorescence signals associated with the acidic TME (Figure 7C).…”

Activatable NIR-II organic fluorescent probes for bioimaging

“…However, its malignant effects were mainly identified using cell and tissue studies 99 , 100 . Thus, monitoring pH levels in living organs is critical for providing information on the physiological and pathological processes 101 - 104 .…”

Fluorescence visualization of deep-buried hollow organs

“…The second near-infrared (NIR-II, 900-1880 nm) window gives a promising fix for deep-penetration biological imaging [1][2][3][4][5][6] . The vessels, lymph, tumor, etc., have been successfully visualized intravitally by virtue of NIR-II fluorescence imaging [7][8][9][10][11][12][13][14][15][16] . Besides the reduced photon scattering, the rising light absorption by water further restrain the scattering disturbance in tissues during NIR-II intravital imaging 17,18 .…”