Exclusive Photothermal Heat Generation by a Gadolinium Bis(naphthalocyanine) Complex and Inclusion into Modified High-Density Lipoprotein Nanocarriers for Therapeutic Applications

A hydrophobic gadolinium bis(naphthalocyanine) sandwich complex (GdSand) possessing several absorbances across visible and infrared wavelengths (up to 2500 nm) was solubilized in aqueous solution by uptake into a nascent mutant high-density lipoprotein (HDL) nanocarrier. The HDL nanocarrier was additionally functionalized with a trans-activator of transcription peptide sequence to promote efficient cell penetration of the drug delivery system (cpHDL). The dye-loaded nanocarrier (GdSand@cpHDL) exhibited photothermal heat generation properties upon irradiation with near-infrared (NIR) laser light, with controllable heat generation abilities as a function of the incident laser light power. Comparison of the photothermal behavior of the dyes GdSand and the well-explored molecular photothermal agent indocyanine green (ICG) in the cpHDL nanocarrier (i.e., ICG@cpHDL) revealed two significant advantages of GdSand@cpHDL: (1) the ability to maintain elevated temperatures upon light absorption for extended periods of time, with a reduced degree of self-destruction of the dye, and (2) exclusive photothermal heat generation with no detectable singlet oxygen production leading to improved integrity of the cpHDL nanocarrier after irradiation. Finally, GdSand@cpHDL was successfully subjected to an in vitro study against NCI-H460 human lung cancer cells, demonstrating the proof-of-principle utility of lanthanide sandwich complexes in photothermal therapeutic applications.