Green Layer-by-Layer Assembly of Porphyrin/G-Quadruplex-Based Near-Infrared Nanocomposite Photosensitizer with High Biocompatibility and Bioavailability

Abstract

A simple and green layer-by-layer assembly strategy is developed for the preparation of a highly bioavailable nanocomposite photosensitizer by assembling near-infrared (NIR) 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. After being efficiently delivered to the target site and internalized into tumor cells via enhanced permeability and retention effect and interactions between aptamers and tumor markers, the as-prepared nanoassembly can be directly used as an NIR light-responsive photosensitizer for tumor photodynamic therapy (PDT) since the porphyrin/G-quadruplex complexes are exposed on the nanoassembly surface and kept in an active state. It can also disassemble under the synergistic stimuli of an acidic pH environment and overexpressed glutathione, leasing more efficient porphyrin/G-quadruplex composite photosensitizers while reducing the interference caused by glutathione-dependent 1O2 consumption. Since the nanoassembly can work no matter if it is disassembled or not, the compulsory requirement for in vivo photosensitizer release is eliminated, thus resulting in the great improvement of the bioavailability of the photosensitizer. The PDT applications of the nanoassembly were well demonstrated in both in vitro cell and in vivo animal experiments.

Aptamer-Targeted Photodynamic Platforms for Tumor Therapy

“…120 Chu et al designed a nanocomposite (FZOA-NPs) for a porphyrin derivative (OMHEP-zEOPP) delivery by assembling amphiphilic short peptides with the metal ions (Zn 2+ ) via a layer-by-layer assembly strategy, and further grafted AS1411 on the surface of FZOA-NPs (Figure 7B). 121 The preparation process only involved amino acid, nucleic acid, organism existed Zn 2+ , and biocompatible porphyrin, obviously reducing the potential toxic during the synthesis process. With the light irradiation at 690 nm, the tumor size of Hela tumor-bearing mice treated with FZOA-NPs was significantly suppressed over other control groups.…”

Applications of Aptamer-Bound Nanomaterials in Cancer Therapy

“…To improve their limited tumor accumulation, many delivery systems have been developed, but biocompatibility is still a big problem. As shown in Figure 11 , Chu et al proposed a strategy [ 119 ]. They first synthesized Fmoc-H/Zn 2+ nanoparticles (FZ-NPs) to load porphyrin/Gquadruplex composite photosensitizers (FZO-NPs), and then the AS1411 aptamer was modified on the surface of FZO-NPs (FZOA-NPs).…”

“… Preparation of FZOA-NPs and their application in tumor PDT treatment. Reprinted with permission from [ 119 ]. Copyright © 2020 American Chemical Society.…”

“…This multifunctional nanosystem may be promising for gastric cancer cells treated in the future. [119]. Copyright © 2010 American Chemical Society.…”

Bioinspired Conjugated Tri-Porphyrin-Based Intracellular pH-Sensitive Metallo-Supramolecular Nanoparticles for Near-Infrared Photoacoustic Imaging-Guided Chemo- and Photothermal Combined Therapy

“…Porphyrin, a conjugated aromatic macrocycle with strong absorption, plays important roles in several biological systems including oxygen transport and enzymes. , It has been widely used in phototherapy. However, most porphyrin-based phototherapeutic agents approved clinically exhibit absorption below 700 nm, which leads to the failure of excitation light to penetrate human tissue effectively. − It is necessary to design new phototherapeutic agents, which show absorption within a biological phototherapy window (700–850 nm). , Highly conjugated porphyrin arrays have received much attention for building NIR absorption materials, , but conjugated porphyrin arrays without functionalization are poorly dispersive in water. , Therefore, the synthesis of highly conjugated and highly dispersed conjugated porphyrin arrays for phototherapy is still a great challenge and has great potential in biomedicine.…”