In Situ Hypoxia-Induced Supramolecular Perylene Diimide Radical Anions in Tumors for Photothermal Therapy with Improved Specificity

Abstract

Considering that hypoxia is closely associated with tumor proliferation, invasion, metastasis, and drug resistance, it is of great significance to overcome hypoxia in tumor treatment. Herein, we report a hypoxia-induced specific photothermal therapy (PTT) based on the photothermal agent of supramolecular perylene diimide radical anions. Hypoxic regions in various tumors display strong reductive ability, and in such environments the supramolecular complex of a perylene diimide derivative and cucurbit [7]uril could be reduced to supramolecular perylene diimide radical anions. Benefiting from the strong NIR absorption and good photothermal conversion performance of the in situ generated supramolecular perylene diimide radical anions, the hypoxia-induced PTT strategy exhibits excellent photothermal therapeutic efficiency as well as good specificity and biological safety. Moreover, hypoxia inducible factor expression of tumors decreases to the normal level after PTT treatment. It is anticipated that such a hypoxia-induced specific PTT strategy opens new horizons for photothermal therapy against hypoxic tumors with improved specificity and safety.

Supramolecular Nanostructures Based on Perylene Diimide Bioconjugates: From Self-Assembly to Applications

“…PDI derivatives have been recognized as an ideal π-conjugated system for chemical, colorimetric and fluorescent sensors [ 12 , 13 ], organic semiconductors and optoelectronic devices [ 14 , 15 , 16 ], phototheranostics, [ 17 , 18 ] as well as bioimaging and gene/drug delivering agents [ 19 ]. Structurally, the PDI molecule is composed of one rigid, planar, and stable perylene core with two imide groups at both ends of the polycyclic aromatic scaffold.…”

Activatable photothermal agents with target-initiated large spectral separation for highly effective reduction of side effects

“…[18][19][20][21][22] Compared with traditional "always-on" photothermal agents, activatable photothermal agents will suppress cancer precisely and minimize side effects on normal tissue. Although it has been reported that various photothermal reagents can be activated by the tumor microenvironment (hypoxia, [23][24][25] lower pH, [26][27][28][29] overexpression of biological enzymes, [30][31][32] and reactive oxygen species (ROS) [33][34][35] ),the majority of them have a signicant shortcoming: heavy spectral overlap between the photothermal agents and their corresponding products. That is, they are unable to achieve true selective activation and minimize side effects on adjacent normal tissues.…”

Efficient photoredox cycles to control perylenediimide self-assembly

“…Specifically, their electron-poor character renders them excellent electron acceptors that can produce stable radical anions. [3] These properties make PDIs promising materials as organic electron-transporting materials (by electron-hole transfer) [4][5][6][7][8] , for water splitting (by electron-transfer) [9,10] , as nearinfrared absorber in photothermal therapy [11][12][13][14] , or as photocatalysts [15,16] . In an example of the latter, König and coworkers showed that a PDI derivative could reduce aryl halides under inert conditions in DMF or DMSO upon photoexcitation of the radical anion state (PDI •-), [15] though the exact mechanism remains to be resolved.…”