Ultrasound-Enhanced Chemo-Photodynamic Combination Therapy by Using Albumin "Nanoglue"-Based Nanotheranostics.

The combination of photodynamic therapy (PDT) and chemotherapy is considered to enhance the antitumor immunity and combat multidrug resistance. Some preclinical studies have reported a positive therapeutic outcome of using ultrasound (US) irradiation to enhance chemotherapy, but the combination of these three modalities has yet to be investigated. On the basis of the discovery of a strong affinity between a photosensitizer sinoporphyrin sodium (DVDMS) and human serum albumin (HSA), a clinically used albumin-paclitaxel (HSA-PTX) nanoparticle is utilized as a "nanoglue" to load a large amount of DVDMS by simple mixing. The five conformations of HSA and DVDMS with highest affinity were calculated using AutoDock Vina. The obtained albumin "nanoglue"-based nanotheranostics, HSA-PTX-DVDMS (HPD), has better fluorescence imaging and PDT performance than free DVDMS, probably due to the reduced quenching of DVDMS after dispersion in albumin. An efficacious tumor-targeting enhancement of chemotherapy by US irradiation is verified in a bilateral subcutaneous 4T1 tumors model. With the aid of US irradiation, the combined PDT and chemotherapy mediated by HPD achieve effective tumor growth inhibition. Overall, this "nanoglue"-based nanotheranostics is composed of several clinically used elements and integrates three clinical modalities with application prospects in clinic.