Bioresponsive prodrug nanogel-based polycondensate strategy deepens tumor penetration and potentiates oxidative stress

Currently single photosensitizers or chemotherapeutics implemented in clinic present huge challenges in terms of non-selective toxicity, physiological instability and unfavorable therapeutic efficacy. Herein, we designed a versatile polycondensate-based strategy for the preparation of redox-responsive prodrug nanogels (NGs) for enhanced synergistic cancer therapy. Concretely, based on a reductive cross-linking of purpurin 18 (P18) and 10-hydroxycamplothecin (HCPT), a well-designed prodrug nanogel (denoted as DPH NGs) with suitable size (similar to 67 nm) was fabricated, which exhibited high drug loading, controlled drug release and deepened tumor penetration. The high concentration of glutathione (GSH) in the tumor microenvironment (TME) is capable of being consumed by dense disulfide bonds in DPH NGs, promoting the generation of reactive oxygen species (ROS) after irradiation at 660 nm, thus reshape the TME to reinforce photodynamic therapy against malignancies. In addition, P18 can be served as a powerful NIR fluorescence (NIRF)/ magnetic resonance (MR) imaging ability. Pleasantly, DPH NGs showed amplified oxidative stress in tumor cells to achieve an enhanced chemophotodynamic therapy with the real-time MR/NIRF dual-modal imaging. Our findings in this study may blow up a storm for devising a simple and versatile strategies for multi-drug delivery and combined cancer therapy.

Automated summary

A versatile polycondensate-based strategy was designed for the preparation of redox-responsive prodrug nanogels to enhance synergistic cancer therapy. The nanogels showed high drug loading, controlled drug release, and deep tumor penetration, while promoting reactive oxygen species generation in the tumor microenvironment. Additionally, the nanogels exhibited dual-modal imaging abilities and achieved enhanced chemophotodynamic therapy.