External Stimuli-triggered Photodynamic and Sonodynamic Therapies in Corporation with Hybrid Nanomicelles of ICG@PEP@HA: Laser vs. Ultrasound

The concept of combining external medical stimuli with internal functional biomaterials to serve cancer-oriented treatments is emergingly developed. Optical and acoustical activations have shown special promises as non-invasive regulation modalities in cancer treatment and intervention. It is always challenging to leverage their contributions between optical and acoustical stimuli and find the appropriate biomaterials to optimally match them. Herein, a type of hybrid nanomicelles (ICG@PEP@HA) containing ICG as photo/sonosensitizers, an amphiphilic peptide for membrane penetration and hyaluronic acid for cluster determinant 44 (CD44) targeting were fabricated. Triggered by external stimuli of laser and US irradiations, their photo/sonothermal performances, in vitro reactive oxygen species (ROS) production capabilities and tumor-targeting efficiency have been systematically evaluated. It was interestingly found that the external stimulus of laser induced more quantity of ROS which resulted in a significant cell apoptosis and tumor growth inhibition in the presence of ICG@PEP@HA. The individual analysis and corresponding rationales have been investigated. In the meanwhile, these hybrid nanomicelles were administered into the MDA-MB-231 tumor-bearing nude mice for PDT and SDT therapies and their biocompatibility assessment, and a PDT prevailing efficacy and reliable bio-safety have been evidenced based on the hematological analysis and histochemical stainings. In summary, this study has validated a novel pathway to utilize these hybrid nanomicelles for laser/US-triggered localized tumor treatments, and the treatment efficiency may be leveraged by different external stimuli sources. It is also expected to give birth to full accessibility to clinical translations for human cancer treatments by means of as-reported laser/US-nanomicelles combination strategy.