Self-Activating Therapeutic Nanoparticle: A Targeted Tumor Therapy Using Reactive Oxygen Species Self-Generation and Switch-on Drug Release

Abstract

One of the recent advances in nanotechnology within the medical field is the development of a nanoformulation of anticancer drugs or photosensitizers. Cancer cell-specific drug delivery and upregulation of the endogenous level of reactive oxygen species (ROS) are important in precision anticancer treatment. Within our article, we report a new therapeutic nanoformulation of cancer cell targeting using endogenous ROS self-generation without an external initiator and a switch-on drug release (ROS-induced cascade nanoparticle degradation and anticancer drug generation). We found a substantial cellular ROS generation by treating an isothiocyanate-containing chemical and functionalizing it onto the surface of porous silicon nanoparticles (pSiNPs) that are biodegradable and ROS-responsive nanocarriers. Simultaneously, we loaded an ROS-responsive prodrug (JS-11) that could be converted to the original anticancer drug, SN-38, and conducted further surface functionalization with a cancer-targeting peptide, CGKRK. We demonstrated the feasibility as a cancer-targeting and self-activating therapeutic nanoparticle in a pancreatic cancer xenograft mouse model, and it showed a superior therapeutic efficacy through ROS-induced therapy and drug-induced cell death. The work presented is a new concept of a nanotherapeutic and provides a more feasible clinical translational pathway.

Glioblastoma Homing Photodynamic Therapy Based on Multifunctionalized Porous Silicon Nanoparticles

“…These results showed that the nanocarrier can stabilize a photolytically unstable ICG and significantly enhance the photodynamic performance (Figure f). , In the release profile analysis of ICG within SIWV-pSiNP­(ICG), 808 nm laser treatment accelerated the release of the incorporated ICG due to ROS generated from ICG, with laser-induced quickened degradation of pSiNPs (Figure g). The produced ROS from ICG accelerated the degradation rate of porous silicon nanoparticles, and the mechanism is that ROS oxidized silicon to silanol (S–OH) formation on the surface of nanoparticles and converted it to the soluble formation (orthosilicic acid, (Si­(OH) 4 )). ,, …”

“…The loading efficiency of ICG was calculated using the following eq 1 (see the Experimental section). 46 The concentration of the unloaded ICG was determined from the standard absorption curve of ICG (Figure S4).…”

“…The produced ROS from ICG accelerated the degradation rate of porous silicon nanoparticles, and the mechanism is that ROS oxidized silicon to silanol (S−OH) formation on the surface of nanoparticles and converted it to the soluble formation (orthosilicic acid, (Si(OH) 4 )). 46,51,52 Prior to the PDT-related study, the cytotoxicity of nanoparticle formulations was evaluated using U87MG (human glioblastoma cell) and Huh7 cell (human hepatoma cell) with CCK-8 assays. Each cell (1 × 10 4 cells/well) was incubated with pSiNP(ICG) and SIWV-pSiNP(ICG) (0−200 μg/mL, 24 h, 37 °C) (Figures S7 and S8).…”

“…The UV/vis absorption spectra of the supernatants from each washing step were measured using a spectrophotometer (Agilent Technologies Cary 8454) to evaluate the loading efficiency of ICG within pSiNP. The concentration of the unloaded ICG within supernatants was calculated from the standard absorption curve (ICG concentration: 0.39–6.25 μg/mL), and the loading efficiency of ICG within the pSiNP was determined using eq …”

“…All living mice were sacrificed on the 20th day, and their tumor tissues were collected for volume measurement. The tumor volume was measured using a caliper and was calculated as V = [(tumor length) × (tumor width) × (tumor depth)]/2, where L is the length, W is the width, and D is the depth of the tumor . Photographic images were captured using a smartphone (Galaxy Z-fold3, Samsung).…”