Cyclized polyacrylonitrile Nanoparticles: Enhanced intratumoral delivery by photocatalysis and collagen denaturation

Currently, cancer treatment remains a significant challenge, primarily due to the intrinsically complex biological characteristics of solid tumors and the elevated tumor interstitial pressure (TIP), which impedes the effective delivery of nanomedicines into the tumor. This interstitial pressure arises from the malignant proliferation of tumor cells, leading to compromised vascular and lymphatic systems, as well as a dense extracellular matrix (ECM). These factors result in the accumulation of interstitial fluid and the deposition of collagen within the tumor. To address this issue, we designed and synthesized cyclized polyacrylonitrile nanoparticles (CPAN NPs) that, upon near-infrared (NIR) light irradiation, facilitate the effective separation of electron (e^-) and hole (h⁺) pairs. This process catalyzes the decomposition of water within the tumor interstitium, generating oxygen, hydrogen, and reactive oxygen species (ROS), thereby reducing interstitial fluid volume and lowering tumor interstitial fluid pressure. Additionally, CPAN NPs exhibit excellent photothermal conversion properties, enabling the denaturation of collagen in the tumor region, which reduces its viscosity and consequently decreases the solid stress within the tumor. Through this "catalysis-protein denaturation" strategy, the TIP level in tumor-bearing mice was reduced by 34.5 %, alleviating the barrier to nanodrug delivery within the tumor interstitium. This led to a 1.64-fold increase in intratumoral drug accumulation. Furthermore, the generated ROS triggered tumor cell apoptosis, effectively inhibiting tumor growth. Thus, this study provides an innovative approach to enhance the deep accumulation of nanodrugs within tumors and improve the efficacy of cancer treatment.