Biodegradable Silica‐Based Nanoparticles with Improved and Safe Delivery of Protoporphyrin IX for the In Vivo Photodynamic Therapy of Breast Cancer

Abstract

Silica-based nanoplatforms are highly versatile and attractive delivery systems for cancer treatment. These platforms have been used for the effective delivery of pharmacological agents in preclinical settings. Though silicon oxide is found naturally in the human body, a major limitation associated with silica-based nanoparticles is their slow biodegradability. Therefore, the potential risks related to the longer bioaccumulation of these materials can be significant. In this work, the synthesis and application of a novel silica-based nanoplatform, polysilsesquioxane nanoparticles (PSilQ NPs) is reported. The developed PSilQ material contains stimuli-responsive properties, and improves biodegradability for the efficient delivery of a clinically relevant photosensitizer, protoporphyrin IX. Herein, it is demonstrated that the PSilQ nanoplatform is biocompatible and exhibits enhanced biodegradability in an immune-competent mouse model. In addition, PSilQ NPs show phototherapeutic efficiency for reducing the tumor burden in an orthotopic model of triple-negative breast cancer. These results may pave the way for the future clinical evaluation of this silica-based nanoplatform.

Functionalization of Photosensitized Silica Nanoparticles for Advanced Photodynamic Therapy of Cancer

“…In this regard, silica nanoparticles (SN) have attracted attention as carriers for drug delivery due to their properties, which include reduced toxicity, good biocompatibility, high surface area, easy functionalization, optical transparency, and low cost [ 56 , 57 ]. PS-loaded silica nanoparticles have been reported as promising singlet oxygen generator platforms, improving the photoactive drug delivery by enhancing PS poor solubility and selectivity for cancer cells [ 58 , 59 , 60 , 61 , 62 ]. The PS can be physically encapsulated or covalently attached to the internal or external surface of the silica nanoparticles [ 63 , 64 , 65 , 66 , 67 ].…”

Light-Activated Protoporphyrin IX-Based Polysilsesquioxane Nanoparticles Induce Ferroptosis in Melanoma Cells

“…This approach was used to develop a degradable PpIX-PSilQ platform for the effective PDT treatment of triple negative breast cancer (TNBC) in vivo [8]. Furthermore, we assessed the multi-modal capability of PpIX-PSilQ NPs by platform for the effective PDT treatment of triple negative breast cancer (TNBC) in vivo [8]. Furthermore, we assessed the multi-modal capability of PpIX-PSilQ NPs by combining PDT, chemotherapy, and gene silencing in the same platform for the treatment of TNBC [9].…”

“…We demonstrated the advantage of using a redox-responsive PpIX-PSilQ platform to enhance the PDT effect in vitro [ 5 , 6 , 7 ]. This approach was used to develop a degradable PpIX-PSilQ platform for the effective PDT treatment of triple negative breast cancer (TNBC) in vivo [ 8 ]. Furthermore, we assessed the multi-modal capability of PpIX-PSilQ NPs by combining PDT, chemotherapy, and gene silencing in the same platform for the treatment of TNBC [ 9 ].…”

“…Recently, ferroptosis has also been studied as an alternative mechanism of PDT to kill cancer cells [ 13 ]. We previously showed that apoptosis is the main mechanism linked to the phototoxicity of PpIX-PSilQ nanoparticles [ 8 ]; however, there is no study reporting the impact of ferroptosis in the PDT effect of this platform. Ferroptosis is an iron-dependent cell death that is caused by extreme peroxidation of cellular phospholipids and is a commonly reported response to tumor radiation therapy [ 14 , 15 ].…”

Functionalization of Photosensitized Silica Nanoparticles for Advanced Photodynamic Therapy of Cancer

“…Silica nanoparticles (SN) have attracted attention as carriers for drug delivery due to their properties, such as reduced toxicity, good biocompatibility, high surface area, easy functionalization, optical transparency, and low cost [49,50]. PS-loaded silica nanoparticles have been reported as promising singlet oxygen generator platforms, improving the photoactive drug delivery by enhancing PS poor solubility and selectivity for cancer cells [51][52][53][54][55]. The PS can be physically encapsulated or covalently attached to the internal or external surface of the silica nanoparticles [56][57][58][59][60].…”