Overcoming ROS Resistance of Photodynamic Therapy with Self‐Assembled Nano‐Prodrugs for Efficient Triple‐Negative Breast Cancer

Abstract

Triple‐negative breast cancer (TNBC) is endowed with a highly aggressive nature that results in distant metastases and high recurrence rates, yet limited success is realized in traditional chemotherapy. Activatable photosensitizers (PSs) may provide an effective and non‐invasive strategy to induce TNBC cell death in a precise way by offering stimuli‐responsive reactive oxygen species (ROS). However, the toxicity of ROS is often mitigated and even devitalized by the instinctive behavior of ROS resistance in TNBC cells. To address this issue, herein a small molecular self‐assembly nano‐prodrug is presented to co‐deliver an activatable PS and ROS resistance inhibitor. In TNBC cells, the overexpressed glutathione can disassemble the nano‐prodrug, thereby releasing ROS resistance inhibitor and activating the PS for photodynamic therapy and fluorescence imaging. A hybrid membrane coating‐assisted nanoparticle formation strategy is further demonstrated for efficient inhibition of tumor growth and distant metastases on both subcutaneous and orthotopic TNBC mice models.

Programmable Singlet Oxygen Battery for Automated Photodynamic Therapy Enabled by Pyridone–Pyridine Tautomer Engineering

“…The synthesis of PS-1 was performed according to previous literature 29 to give compound 14, followed by an aldol reaction to give the final compound PS-1(10) with a 67% yield. Both compounds were fully characterized by 1 H nuclear magnetic resonance (NMR), 13 C NMR, and high-resolution mass spectrum (HR-MS) (Figures S4−S12) to reveal their right structures with high purity.…”

“…Photodynamic therapy (PDT) has been explored as a noninvasive, high-efficiency cancer treatment strategy that kills cancer cells by using photosensitizers (PSs) to generate reactive oxygen species (ROS). − Importantly, this mechanism allows PDT to be effective against cancers that have developed multidrug resistance to traditional chemotherapeutics . However, the tumor hypoxic environment has become a significant problem that limits the application of PDT, as traditional photosensitization processes employ oxygen-dependent approaches.…”

A POSS-Based Metal-Phenolic Network with Coupled Hardness and Softness for Photodynamic-Immunotherapy of Triple-Negative Breast Cancer

“…6−9 Therefore, PDT allows for more precise treatment with significantly reduced side effects, compared to traditional treatment methods for TNBC such as surgical procedures or chemotherapy. 10,11 However, most of the reported PS is strongly hydrophobic, due to their rigid planar structure, 12,13 leading to compromised PDT efficiency. In this regard, the recently developed PS with aggregation-induced luminescence effects can solve the aggregation fluorescence quenching drawback of conventional PS.…”

“…Photodynamic therapy (PDT) serves as an emerging approach to treat malignant diseases with photosensitive drugs upon laser activation. Specifically, in the PDT process, irradiating the tumor with specific wavelengths to activate photosensitizers (PS) in the tumor tissue not only triggers photosensitization but also subsequent immunogenic cell death (ICD) induction. − Therefore, PDT allows for more precise treatment with significantly reduced side effects, compared to traditional treatment methods for TNBC such as surgical procedures or chemotherapy. , However, most of the reported PS is strongly hydrophobic, due to their rigid planar structure, , leading to compromised PDT efficiency. In this regard, the recently developed PS with aggregation-induced luminescence effects can solve the aggregation fluorescence quenching drawback of conventional PS. − Still, the complexity of the synthesis routes has limited their clinical translation potentials.…”