Control of the incorporation and release of guest molecules by photodimerization in liposomes

In a drug-delivery system using liposomes, the use of guest molecules bearing hydrophilic moieties results in some leakage from lipid membranes. We suppressed the leakage of coumarins (used as model guest molecules in a drug-delivery system) from lipid membranes by photodimerization at 365 nm. The reason for this phenomenon could be ascribed to an increase in the hydrophobicity of the dimers of the coumarins. The formation of the dimers was detected by 1H NMR, UV-vis absorption, and mass spectra and the leakage percentages of the coumarins were determined by 1H NMR spectra based on the peak intensities. In contrast, when the dimer reverted to a monomer by ultraviolet (254 nm) irradiation, the resulting monomer was released from liposomes.This work was supported by a JSPS KAKENHI Grant-in-Aid for Scientific Research (B) (Grant No. JP16H04133) and a Grant-in-Aid for Challenging Exploratory Research (Grant No. JP16K13982)

Different stabilities of liposomes containing saturated and unsaturated lipids toward the addition of cyclodextrins

Liposomes composed of unsaturated lipids were more stable than those containing saturated lipids toward DMe‐β‐CDx, DMe‐α‐CDx and DMe‐β‐CDx. The Hill coefficient values (n) indicated that the saturated lipid•DMe‐CDx complexes had stoichiometric ratios in the range of 1:3‒1:4, while the unsaturated lipid•DMe‐CDx complexes had ratios in the range of 1:1.5‒1:3. That is, a cis alkene group in the unsaturated lipids prevented complexation with a second DMe‐CDx in the direction toward each acyl chain. Furthermore, the liposomes composed of the unsaturated lipids were much slower to form precipitates upon the addition of α‐CDx than those of the saturated lipids. To the best of our knowledge, this is the first example showing that CDxs interact with unsaturated lipids.This work was supported by the Japanese Society for the Promotion of Science (JSPS) KAKENHI a Grant‐in‐Aid for Scientific Research (B) (Grant No. 25288037 and No. 16H04133) and a Grant‐in‐Aid for Challenging Exploratory Research (Grant No. 16K13982)

Reversible Supramolecular System of Porphyrin Exchange between Inclusion in Cyclodextrin and Intercalation in DNA by Change in pH

Under the coexistence of cyclodextrin and DNA in water, 5,10,15,20-tetra(4-pyridyl)porphyrin interacted with the cavities of two cyclodextrin molecules in a solution at an around neutral pH and intercalated into DNA under acidic conditions. The supramolecular phenomena occurred completely and reversibly owing to the change in pH.This work was supported by a JSPS KAKENHI Grant-in-Aid for Scientific Research (B) (Grant No. JP16H04133) and a Grant-in-Aid for Challenging Exploratory Research (Grant No. JP16K13982)

Incorporation of large guest molecules into liposomes via chemical reactions in lipid membranes

The incorporation of hydrophobic guest molecules into lipid membranes by the exchange of the guest molecule from a cyclodextrin (CDx) complex to a liposome is limited to guest molecules that can be included in CDxs. To solve this problem, large guest molecules were incorporated into liposomes by chemical reactions of guest molecules in lipid membranes. Stable lipid-membrane-incorporated fullerene derivatives with large substituent(s) were prepared by Diels–Alder reactions in lipid membranes.Electronic supplementary information (ESI) available: Schematic representation of the premixing and exchange methods, 1H NMR spectra and UV-vis absorption spectra. See DOI: 10.1039/c6ob02343fThis work was supported by the Japanese Society for the Promotion of Science (JSPS) KAKENHI Grant-in-Aid for Scientific Research (B) (Grant No. JP16H04133) and a Grant-in-Aid for Challenging Exploratory Research (Grant No. JP16K13982)

Formation of lipid membrane‐incorporated small π‐molecules bearing hydrophilic groups

Nineteen poorly water‐soluble π‐conjugated molecules were evaluated in terms of their ability to be stably incorporated into lipid membranes. The resulting lipid membrane-incorporated π‐conjugated guest molecules (LMIGs) were classified into four categories, including (i) those that formed stable LMIGs; (ii) those where some of guest molecules precipitated; (iii) those that formed small self‐aggregates consisting of lipids and/or guest molecules; and (iv) those that leaked some of the guest molecules into the bulk water. Compounds belonging to category (ii) were confirmed by UV‐vis absorption analysis. In contrast, compounds belonging to categories (i), (iii) and (iv) were discriminated based on their 1H NMR spectra and the broadening or disappearance of the peaks of the guest molecules and the lipids in LMIGs and large liposomes. Several LMIGs could be converted from one category to another using other lipids. Furthermore, the guest molecules belonging to category (iv) were successfully predicted using the octanol‐water partition coefficient, which was calculated by simulation.This work was supported by the Japanese Society for the Promotion of Science (JSPS) KAKENHI Grant‐in‐Aid for Scientific Research (B) (Grant No. JP16H04133) and a Grant‐in‐Aid for Challenging Exploratory Research (Grant No. JP16K13982)

Adsorption of tetrakis(4-sulfophenyl)porphyrin onto liposomal surfaces composed of neutral diacylphosphatidylcholine and release by cyclodextrin

Anionic tetrakis(4-sulfophenyl)porphyrin (TPPS) interacts with liposomal surfaces composed of neutral diacylphosphatidylcholine at high lipid concentrations. TPPS interacted with liposomal surfaces through four contact points. The association constant was obtained to be 9.0 × 10^5 M^-4. TPPS was peeled off the liposomal surfaces by the addition of cyclodextrin.Electronic supplementary information (ESI) available: Experimental procedures and UV-vis absorption and 1H NMR spectra. See DOI: 10.1039/c8ra01411fThis work was supported by a JSPS KAKENHI Grant-in-Aid for Scientific Research (B) (Grant No. JP16H04133) and a Grant-in-Aid for Challenging Exploratory Research (Grant No. JP16K13982)

Lipid-membrane-incorporated arylboronate esters as agents for boron neutron capture therapy

Arylboronate esters bearing methyl groups in both of their ortho positions were stably incorporated into lipid membranes at high concentrations without undergoing hydrolysis to the corresponding boronic acids. This method could be used in combination with previous methods to increase the maximum ratio of boron atoms in liposomal boron carriers.This work was supported by a JSPS KAKENHI Grant-in-Aid for Scientific Research (B) (Grant No. JP16H04133) and a Grant-in-Aid for Challenging Exploratory Research (Grant No. JP16K13982)

Improvement of Photodynamic Activity of Lipid-Membrane-Incorporated Fullerene Derivative by Combination with a Photo-Antenna Molecule

The weak absorbance of pristine C60, C70, and fullerene derivatives at wavelengths over 600 nm hampers the use of these molecules as photosensitizers (PSs) for photodynamic therapy (PDT). The coexistence of light-harvesting antenna molecules with a fullerene derivative in lipid membrane bilayers solved this issue. By controlling the location of the C60 derivative in the lipid membrane, the liposomal dyad system for PDT improved the photodynamic activity via an efficient photoenergy transfer from antenna molecules to the fullerene derivative. The photodynamic activity was found to be much higher than those of dyad systems using pristine C60 and C70.This work was supported by a JSPS KAKENHI Grant-in-Aid for Scientific Research (B) (Grant No. JP16H04133) and a Grant-in-Aid for Challenging Exploratory Research (Grant No. JP16K13982)

Lipid-membrane-incorporated hydrophobic photochromic molecules prepared by the exchange method using cyclodextrins

It was found that the exchange method for the preparation of lipid-membrane-incorporated guest molecules was applicable not only to fullerenes but also to other hydrophobic molecules such as azobenzene and stilbene. Advantages of this method are that the long-term stability of lipid-membrane-incorporated azobenzene solution and the maximum ratio of [stilbene]/[lipid] were higher than those prepared by the classical method, which we call the ‘premixing method’. Photoisomerisations of these photochromic guest molecules in the lipid membranes maintained the morphology of liposomes.This file includes Electronic Supplementary Information.This work was supported by JSPS KAKENHI a Grant-in-Aid for Scientific Research (B) (Grant No. 25288037), a Grant-in-Aid for Challenging Exploratory Research (Grant Nos. 24655128 and 25650053) and a Grant-in-Aid for Young Scientists (A) (Grant No. 24681028)

Formation of β‐(1,3‐1,6)‐D‐glucan‐complexed [70]fullerene and its photodynamic activity towards macrophages

[70]Fullerene was dissolved in water by the complexation with β‐1,3‐glucan using a mechanochemical high‐speed vibration milling apparatus. The photodynamic activity of β‐1,3 glucan‐complexed C70 was highly dependent on the expression level of dectin‐1 on the cell surfaces of macrophages. The photodynamic activity increased as a result of a synergistic effect between β‐1,3‐glucan‐complexed 1’‐acetoxychavicol acetate and the C70 complex.This work was supported by JSPS KAKENHI Grant‐in‐Aid for Scientific Research (B) (Grant No. JP16H04133), Grant‐in‐Aid for Scientific Research (C) (Grant No. 26350528) and Grant‐in‐Aid for Challenging Exploratory Research (Grant No. JP16K13982)