A Two‐In‐One Nanoprodrug for Photoacoustic Imaging‐Guided Enhanced Sonodynamic Therapy

Abstract

Sonodynamic therapy (SDT) is garnering considerable attention in cancer treatment due to its non‐invasive nature and the potential of spatiotemporal control. However, the high level of glutathione (GSH) in cancer cells can alleviate the SDT‐mediated ROS‐damages, resulting in a reduced SDT effect. Here, a two‐in‐one nano‐prodrug for photoacoustic imaging‐guided enhanced SDT against skin cancers is synthesized. A dual‐prodrug molecule (DOA) of sulfide dioxide (SO2) and 5‐aminolevulinic acid (ALA) is first synthesized and then co‐assembled with methoxyl poly(ethylene glycol)‐b‐poly(l‐lysine) (mPEG‐b‐PLL) to generate the two‐in‐one prodrug nanoparticles (P‐DOA NPs). The P‐DOA NPs simultaneously released ALA and SO2 in response to the overexpressed GSH in tumor cells. The released ALA is metabolically converted into protoporphyrin IX (PpIX) in tumor cells for SDT and photoacoustic imaging. Meanwhile, the released SO2, together with the consumption of GSH based on the reaction of DOA in P‐DOA NPs with intracellular GSH, can significantly increase the intracellular ROS content, leading to enhanced SDT. As a result, the P‐DOA NPs significantly inhibited the growth of melanoma and squamous cell carcinoma xenografts in mouse models under the guidance of real‐time photoacoustic imaging. Therefore, this novel two‐in‐one nano‐prodrug is promising for effective SDT against skin cancers.

Amplifying the efficacy of ALA-based prodrugs for photodynamic therapy using nanotechnology

“…However, high concentration of GSH in tumor cells would alleviate SDTinduced ROS damage, thus reducing the SDT effects (Kumar et al, 2022). To this end, Sun and coworkers reported a two-inone GSH-responsive nanoprodrug for photoacoustic imagingguided SDT for skin cancer (Sun et al, 2022). The two-in-one prodrug nanoparticles (P-DOA NPs) were co-assembled from methoxyl poly(ethylene glycol)-b-poly(l-lysine) (mPEG-b-PLL) and the GSH responsive DOA fragment was synthesized by 2,4dinitrobenzenesulfonyl chloride (DNs-Cl) and ALA.…”

Recent progress in metal–organic framework-based sonosensitizers for sonodynamic tumor therapy

“…113 Therefore, in theory, the gaseous molecules would cooperate with ROS produced by SDT to increase overall damage, thereby enhancing treatment efficacy. Currently, several gaseous molecules have already been used in SDT–gas combination therapy, including carbon monoxide, 114 nitric oxide, 115 sulfide dioxide, 116 and hydrogen sulfide. 117 It should be noted that the generation of microbubbles or gas bubbles 118 during SDT is not considered part of the gas therapeutic molecules, as they do not act on mitochondria but cause cell death through mechanical damage from bubble bursting.…”

Recent advances in nanomaterials for the treatment of spinal cord injury

“…The applications of functional nanomaterials in biomedical research are well documented, especially in the field of cancer [ [10] , [11] , [12] ]. In recent years, therapeutic nanoparticles (NPs) and their delivery have also attracted widespread attention as an emerging engineering technology for SCI treatment [ 13 ], and nanotheranostics have shown advantages in multiple aspects.…”