Quantitative and Site-Directed Chemical Modification of Hypocrellins toward Direct Drug Delivery and Effective Photodynamic Activity

Abstract

For photodynamic therapy (PDT) treatment of microvascular diseases, drugs are delivered via blood circulation and the targets are vasculature endothelial cells, for which the contradictory requirements of hydrophilicity and lipophilicity of the drugs have been achieved by liposome preparations. Herein, it is demonstrated that the drug delivery and target affinity are achieved by a single chemical compound, hypocrellin B (HB) derivative 6 selected from three novel aminoalkanesulfonic acid HB derivatives, 5-7. 6 exhibits a much higher PDT activity (IC(50) = 22 nM) on human gastric carcinoma BGC823 cells than HB, while it has no cellular toxicity in the dark. On the basis of estimation of the clinically required concentration according to relative PDT activity and clinical criteria, it can be predicted that 6 is directly deliverable to and PDT effective on target cells. The enhanced red absorption and superhigh photoactivity suggest that 6 is more powerful for PDT of tumors than HB.

Drug-delivery and multifunction possibilities of hypocrellin photosensitizers

“…4). 35,64 Interestingly, it was found that the aqueous solubility and PC formed linearly decreasing and increasing sequence with increase in the carbon number, in addition, the singlet oxygen yield increased gradually with the carbon atom number, as shown in Fig. 5.…”

“…Consequently, it exhibited much higher PDT activity to human gastric cancer BGC823 cells than the parent HB, with the IC 50 (de¯ned as the photosensitizer concentration required killing 50% of the cells) of 22 nM compared with that of 40 nM for HB, in addition, it had no dark cellular toxicity. 35 It can be concluded that 6 possesses the optimized amphiphilicity and PDT activity, and can be directly used for intravenous injection without need of preparation of drug-delivery vehicles.…”

“…Consequently, in a viewpoint of clinical requirement for drugdelivery, an ideal derivative should have a quantitative instead of qualitative amphiphilicity, i.e., the lipophilicity should be kept as large as possible as long as the aqueous solubility satis¯es the clinically required concentration of the drug. 34 Generally, clinically required concentration (C) could be estimated according to the following equation 35 :…”

Enhanced hypocrellin production of Shiraia sp. SUPER-H168 by overexpression of alpha-amylase gene

“…These compounds are isolated from the stromata of Hypocrella bambusae and Shiraia bambusicola . Hypocrellins and their derivatives [ 5 – 7 ] have gained considerable attentions for two decades, because they can accumulate selectively in cancer cells and their excellent light-induced antiviral activities against tumours and viruses, especially the antiviral activities against the human immunodeficiency virus (HIV) [ 8 ]. In addition to benefiting the pharmaceutical industry, hypocrellins also have extensively potential applications in the agricultural, cosmetic, food, and feed industries [ 9 – 11 ].…”

Liposomal hypocrellin B as a potential photosensitizer for age-related macular degeneration: pharmacokinetics, photodynamic efficacy, and skin phototoxicity in vivo

“…However, HB is a hydrophobic drug and its solubility must be improved in order to maximize its potential bioavailability. One strategy to improve the HB solubility is chemical modification, [28][29][30] but most of the HB derivatives generated to date have exhibited less PDT efficacy than their parent. [31][32][33] This solubility conundrum could be addressed by the use of an alternative pharmaceutical-based strategy.…”