Visible Light-Responsive Delivery of Two Anticancer Drugs Using Single-Component Fluorescent Organic Nanoparticles

Abstract

Combination therapy is a promising strategy to improve therapeutic efficiency and minimize side effects. So far, the C9-functionalized acridine derivatives were employed as photocages to deliver only one active molecule. Here, we have developed a C4, C5-substituted dual-arm acridine photocage for the first time to release two carboxylic acids and amino acids simultaneously. As a proof of concept, we have constructed a visible light-responsive dual drug delivery system (Acr-Cbl-Vpa) and made it single-component fluorescent organic nanoparticles (NPs) to deliver two anticancer drugs (chlorambucil and valproic acid). Acr-Cbl-Vpa NPs can accumulate inside the cell nucleus, and the planer motif allows the photocage to intercalate with the DNA and maximize the cancer cell killing ability of the drugs. In vitro studies with cancerous HeLa cell lines showed that Acr-Cbl-Vpa NPs displayed improved anticancer efficacy and real-time fluorescence monitoring of the drug release.

Visible Light Degradable Acridine-Containing Polyurethanes in an Aqueous Environment

“…It is interesting to note that exclusive formation of the acridine diol 3 was observed, indicating simultaneous photolysis of the two carbamate bonds within the compound under irradiation. While the photoinduced hydrolysis of the 9methyl ester 36,37 or 4,5-dimethyl ester acridine 38 derivatives in acetonitrile/water has been reported, we herein showed the photolysis of the methyl carbamate substituents can happen in a DMSO/water. We further suggest the photoinduced hydrolysis mechanism similar to that of the photolysis of the 4,5-dimethyl ester acridine (Scheme S2), in which the singlet excited state of the acridine moiety undergoes heterolytic cleavage assisted by protic solvents.…”

“…While the photoinduced hydrolysis of the 9-methyl ester , or 4,5-dimethyl ester acridine derivatives in acetonitrile/water has been reported, we herein showed the photolysis of the methyl carbamate substituents can happen in a DMSO/water. We further suggest the photoinduced hydrolysis mechanism similar to that of the photolysis of the 4,5-dimethyl ester acridine (Scheme S2), in which the singlet excited state of the acridine moiety undergoes heterolytic cleavage assisted by protic solvents . The simultaneous photohydrolysis of the two carbarmate groups may be due to the presence of excess water.…”

“…The quantum yield of the photolysis at λ max = 405 nm is lower than that of the photolysis of the diester derivatives, which were in the range of 0.02−0.05. 38 It could be seen that while the absorbance of 1 decrease by 4-fold at 405 nm (2.553 × 10 3 L•mol −1 •cm 2 ) compared to 365 nm (1.014 × 10 4 L•mol −1 •cm 2 ), the quantum efficiency of the photolysis only decreases slightly. Interestingly, photolysis could happen with good efficiency at irradiation wavelength of 440 nm, where there is almost no absorbance.…”

“…The quantum yield under three different irradiation wavelengths at λ max = 365, 405, and 440 nm were estimated to be 5.47 × 10 –3 , 4.53 × 10 –3 , and 2.42 × 10 –3 , respectively. The quantum yield of the photolysis at λ max = 405 nm is lower than that of the photolysis of the diester derivatives, which were in the range of 0.02–0.05 . It could be seen that while the absorbance of 1 decrease by 4-fold at 405 nm (2.553 × 10 3 L·mol –1 ·cm 2 ) compared to 365 nm (1.014 × 10 4 L·mol –1 ·cm 2 ), the quantum efficiency of the photolysis only decreases slightly.…”

“…We further suggest the photoinduced hydrolysis mechanism similar to that of the photolysis of the 4,5-dimethyl ester acridine (Scheme S2), in which the singlet excited state of the acridine moiety undergoes heterolytic cleavage assisted by protic solvents. 38 The simultaneous photohydrolysis of the two carbarmate groups may be due to the presence of excess water.…”