Plasmid DNA‐Based Bioluminescence‐Activated System for Photodynamic Therapy in Cancer Treatment

Abstract

The low depth of tissue penetration by therapeutic light sources severely restricts photodynamic therapy (PDT) in treating deep‐seated tumors. Using a luciferase/d‐luciferin bioluminescence system to artificially create internal light sources in cells instead of external light sources is an effective means of solving the above problems. However, high‐efficiency bioluminescence requires a higher concentration of luciferase in the cell, which poses a considerable challenge to the existing system of enzyme loading, delivery, activity and retention of drugs, and dramatically increases the cost of treatment. We loaded the substrate D‐luciferin, and the photosensitizer hypericin into a polyethyleneimine (PEI)‐modified nano‐calcium phosphate (CaP) to solve this problem. Subsequently, the plasmid DNA containing the luciferase gene was loaded onto it using the high‐density positive charge characteristic of PEI from the nanodrug (denoted DHDC). After the DHDC enters the tumor cell, it collapses and releases the plasmid DNA, which uses the intracellular protein synthesis system to continuously and massively express luciferase. Using endogenous ATP, Mg2+, and O2 in cells, luciferase oxidizes d‐luciferin and produces luminescence. The luminescence triggers hypericin excitation to generate ROS and kill cancer cells. This study provides a new strategy for the application of bioluminescence in PDT treatment.

Enzyme/pH Dual-Responsive Size-Shrinkable Nanocomposites for Tumor Penetration and Enhanced Multimodal Cancer Therapy

“…Furthermore, there was a positive correlation between the concentration of CuS-PEI and the intracellular accumulation of ROS during the same radiation exposure. The accumulation of high concentrations of ROS inside tumor cells can oxidize macromolecules such as DNA and protein and promote the apoptosis of tumor cells …”

“…The accumulation of high concentrations of ROS inside tumor cells can oxidize macromolecules such as DNA and protein and promote the apoptosis of tumor cells. 55 We further evaluated the synergistic effect of PDT and PTT. The red fluorescence in Figure 6D represents (Lyso-Tracker red) the living cells and the white circle represents the central area illuminated by the laser.…”

Towards overcoming obstacles of type II photodynamic therapy: Endogenous production of light, photosensitizer, and oxygen

“…An alternative approach is to deliver the gene encoding Fluc instead of Fluc proteins. A nanomedicine was developed by encapsulating d -luciferin, hypericin, and a plasmid inserted with the Fluc gene in polyethyleneimine-modified nano calcium phosphate 55 ( Fig. 2 B).…”

Tumor Diagnosis and Therapy Mediated by Metal Phosphorus‐Based Nanomaterials

“…However, the coprecipitation strategy of metal phosphate nanomaterials at room temperature faces the challenge of uncontrolled growth, which leads to the inevitable aggregation of nanoparticles. [ 12d ] To overcome above barriers, the addition of polymers [ 35,36 ] and surfactants, [ 37 ] such as polyethyleneimine (PEI), polyacrylic acid (PAA), cetyltrimethylammonium bromide, poly(styrene‐acrylic acid‐ethylene glycol) (PS‐PAA‐PEG), poly(diallyldimethylammonium chloride), and poly (acrylate sodium) was used to control the formation of nanoparticles and enhance their stability. However, the potential biological toxicity of some polymers and surfactants also restricts the application of metal phosphates.…”