Conclusions
The results reveal the great clinical potential of our PGA-based nanosystems as a tool for holistic melanoma treatment management.
Methods
To meet this challenge, we designed novel polymeric imaging and therapeutic systems, implemented in a two-step theranostic approach. Both are composed of the biocompatible and biodegradable poly(α,L-glutamic acid) (PGA) nanocarrier that facilitates extravasation-dependent tumor targeting delivery. The first system is a novel, fluorescent, Turn-ON diagnostic probe evaluated for the precise excision of the primary tumor during image-guided surgery (IGS). The fluorescence activation of the probe occurs via PGA degradation by tumor-overexpressed cathepsins that leads to the separation of closely-packed, quenched FRET pair. This
Results
IGS in melanoma-bearing mice led to a high tumor-to-background ratio and reduced tumor recurrence in comparison with mice that underwent surgery under white light (23% versus 33%, respectively). Adjuvant therapy with PGA-SLM-mDBF combined with ICPi, was well-tolerated and resulted in prolonged survival and prevention of peritoneal and brain metastases formation in BRAF-mutated melanoma-bearing mice. Conclusions: The results reveal the great clinical potential of our PGA-based nanosystems as a tool for holistic melanoma treatment management.