Repurposing Cyanine Photoinstability To Develop Near-Infrared Light-Activatable Nanogels for In Vivo Cargo Delivery

Abstract

The favorable properties of cyanines (e.g., nearinfrared (NIR) absorbance and emission) have made this class of dyes popular for a wide variety of biomedical applications. However, many cyanines are prone to rapid photobleaching when irradiated with light. In this study, we have exploited this undesirable trait to develop NIR-nanogels for NIR light-mediated cargo delivery. NIR-nanogels feature a photolabile cyanine crosslinker (Cy780-Acryl) that can cleave via dioxetane chemistry when irradiated. This photochemical process results in the formation of two carbonyl fragments and concomitant NIR-nanogel degradation to facilitate cargo release. In contrast to studies where cyanines are utilized as photocages, our approach does not require direct chemical attachment to the cargo, thus expanding our ability to deliver molecules that cannot be covalently modified. We showcase this feature by encapsulating a palette of small-molecule chemotherapeutics that feature a structurally diverse chemical architecture. To demonstrate site-selective release in vivo, we generated a murine model of breast cancer. Relative to nonlight irradiated and drugfree controls, treatment with NIR-nanogels loaded with paclitaxel (a potent cytotoxic agent) and NIR light resulted in significant attenuation of tumor growth. Moreover, we show via histological staining of the vital organs that minimal off-target effects are observed.

NIR Light-Activated Mitochondrial RNA Cross-Linking Strategy for H2S Monitoring and Prolonged Colorectal Tumor Imaging

“…The spectral characteristics of Cy796 and Cy758 were investigated in physiological buffer solutions (pH = 7.4). The planar structure of heptamethine limited its aqueous solubility, and the polymethine structure can be easily photobleached after exposure with 1 O 2 . − The stability of two probes was first tested. As shown in Figure S1a,b, Cy796 exhibited slight absorbance fluctuations at 825 nm, while Cy758 has prominent changes at 833 nm with the generation of a new absorbance peak at 670 nm in 96 h, indicating the comparative stabilization of Cy796 than that of Cy758.…”

Aggregation-Induced Emission (AIE), Life and Health

“…With enhanced light penetration and lower background signals, near-infrared (NIR) imaging can offer improved performance when compared with traditional techniques at the shorter wavelength region. − Taking advantage of the AIE features and their long emission wavelength, NIR AIEgens can not only provide desirable photostability and enhanced fluorescence efficiency in aggregates but also exhibit reduced tissue scattering, enhanced penetration depth, diminished autofluorescence, and minimal photodamage to biological tissues. − A win-win cooperation could be achieved by combining NIR emission into luminogens with AIE characteristics, enabling better bioimaging quality and rapid development for biological applications.…”

Optical and Photoacoustic Imaging In Vivo: Opportunities and Challenges

“…As an externally controlled stimulation, light allows real-time, noninvasive, and high local accuracy manipulation toward a light-responsive nanoplatform by simply adjusting the power, wavelength, and exposure duration. Compared with traditional visible light, NIR light shows higher penetration toward biological tissues . Our group designed a NIR light-activated nanoplatform combining Au nanorods (AuNRs) such as NIR-II PA imaging probes with IR-1061 and NIR-II FL imaging probes .…”

“…Compared with traditional visible light, NIR light shows higher penetration toward biological tissues. 49 Our group designed a NIR light-activated nanoplatform combining Au nanorods (AuNRs) such as NIR-II PA imaging probes with IR-1061 and NIR-II FL imaging probes. 50 When the probes were assembled with the Rucomplex and PEG, the NIR-II PA signal was enhanced while the NIR-II FL signal of IR-1061 was quenched due to the LSPR effect of AuNRs.…”