Lipid‐DNAs as Solubilizers of mTHPC

Abstract

Hydrophobic drug candidates require innovative formulation agents. We designed and synthesized lipid‐DNA polymers containing varying numbers of hydrophobic alkyl chains. The hydrophobicity of these amphiphiles is easily tunable by introducing a defined number of alkyl chain‐modified nucleotides during standard solid‐phase synthesis of DNA using an automated DNA synthesizer. We observed that the resulting self‐assembled micelles solubilize the poorly water‐soluble drug, meta‐tetra‐hydroxyphenyl‐chlorin (mTHPC) used in photodynamic therapy (PDT) with high loading concentrations and loading capacities. A cell viability study showed that mTHPC‐loaded micelles exhibit good biocompatibility without irradiation, and high PDT efficacy upon irradiation. Lipid‐DNAs provide a novel class of drug‐delivery vehicle, and hybridization of DNA offers a potentially facile route for further functionalization of the drug‐delivery system with, for instance, targeting or imaging moieties.

Delivery system for budesonide based on lipid-DNA

“…UU11mer, which contains two modified uracil bases (Fig. 1b), where U represents the modified uracil base) was synthesized according to the published procedure [32]. The CMC was determined to be 29 µM for UU11mer.…”

“…Lipid-modified oligonucleotide UU11mer (5'-UUTGGCGTCTT-3') with two modified uracils (U represents the modified uracils) was prepared by using solidphase synthesis [32].…”

“…Despite various amphiphilic materials being used [30], it is still a challenge to construct a biocompatible and effective micellar drug-delivery systems. Previous studies have shown that lipid-DNA amphiphiles, consisting of a hydrophilic DNA moiety and hydrophobic alkyl tails, can undergo self-assembly into micelles, leading to potential nanocarriers of hydrophobic drugs [31,32]. Owing to their small size and the use of biocompatible DNA as a component, these nanocarriers provide several advantages including: (1) high drug loading capacity (LC) attributed to the interactions of hydrophobic interactions between the drugs and the hydrophobic interior; (2) improved biocompatibility by reducing the dose; (3) automated synthesis [33,34]; and (4) ease of modification by taking advantage of DNA hybridization to endow ligand-receptor-mediated drug targeting properties (such as folic acid to sites of inflammation [35]).…”

“…Based on the above considerations, the aim of this study is to investigate a lipid-DNA amphiphile, UU11mer [32], featuring two hydrophobic alkyl chains ( Fig. 1d), that forms micelles at comparatively low critical micelle concentration (CMC) as solubilizers of budesonide ( Fig.…”

The Photosensitizer Temoporfin (mTHPC) – Chemical, Pre‐clinical and Clinical Developments in the Last Decade†‡

“…The utility of the concept was further tested by comparing the solubilization of three related tetrapyrrole‐based photosensitizers, temoporfin, chlorin e 6 , and pheophorbide a, finding significant binding capacity differences (357). Apart from peptides, the concept was additionally investigated, using temoporfin as a model drug, with lipid‐DNA (143), thiolactone polymers (358), peptoid sequences (359), and alternating co‐polymers (360).…”