The Assembly Of Porphyrin/G-Quadruplex-Based Near-Infrared Nanocomposite Photosensitizers And The Application In Photodynamic Therapy

Porphyrins and their derivatives have great potential as photosensitizers(PSs)in the photodynamic therapy(PDT)of cancer,which have been the focus of research in recent years.G-quadruplex is a kind of unique nucleic acid secondary structure.The latest research work of our research group shows that G-quadruplex can be specifically complexed with the prepared cationic porphyrins with a large side arm substituent,and the complex has enhanced light absorption capacity in the biological transparent window,thereby expected to form a kind of near infrared composite photosensitizer.Based on the existing research on porphyrins in the research group and related research work on new nanocomponents in recent years,two new types of nano Composite photosensitizers are constructed with peptide nanocarriers and DNA nanostructures with good biocompatibility,respectively.In order to solve a series of problems such as the small penetration depth of light in biological tissues in PDT and hinder its application in the treatment of deep tumors,the potential side effects caused by residual PSs absorbing white light,low bioavailability,low biosafety and PSs passively targeted into cells,lacking active targeting and so on.Based on the research on porphyrins in our research group and the novel nanocomposites reported in the literature in recent years,two novel nanocomposite photosensitizers were developed,constructed with peptide nanocarriers and DNA nanostructures with good biocompatibility.The main contents are as follows:1.A simple and green layer-by-layer strategy is developed for the preparation of a highly bioavailable nanocomposite photosensitizer by assembling near-infrared light-sensitive porphyrin/G-quadruplex complexes on the surface of a highly biocompatible nanoparticle that is prepared via Zn²⁺-assisted coordination self-assembly of an amphiphilic amino acid.The prepared nanocomposite photosensitizer showed a series of attractive characteristics,such as simple and green synthesis,low dark toxicity and good biocompatibility,improved tumor accumulation,elimination of the compulsory requirement for photosensitizer release,strong absorption to NIR light,highly efficient¹O₂generation,high bioavailability,and reduced interference from glutathione.Its application potential was well demonstrated in both in vitro and in vivo experiments.2.A novel nanocomposite photosensitizer based on DNA nanostructure is constructed.The nanocomposite photosensitizer is formed by assembling a DNA nanolantern prepared from 4 oligonucleotides and porphyrin/G-quadruplex complex through a complementary base pairing of a specific partial sequence,which gives high efficiency,strong absorption of near-infrared light,efficient¹O₂generation,good biocompatibility,good dark toxicity and other advantages.Thus,it has a great application potential in the clinical PDT treatment of solid tumors.