Abstract: New advantageous compositions and methods for treatment of malignancies such as basel cell carcinoma and other skin cancers, brain tumors, head and neck cancer, kidney cancer, prostate cancer and other cancer types. The new compositions and methods may also be used for treatment of non-cancer problems such as dermatological diseases, sexual diseases, anti-fungal and antibacterial and wound healing. A new photodynamic therapy/sonodynamic therapy (PDT/SDT) combination approach using near infrared (NIR) tetrapyrrolic photosensitizers (PSs) with long wavelength absorption, in the range of 750-800 nm, that provides deeper tissue penetration. Such combinations may be postloaded onto PAA nanoparticles (NPs) for better delivery to a tumor site. A preferred sonodynamic compound is fullerene 60 but other sonodynamic compounds may be employed. The unique NP formulations of the invention can contain chemotherapeutic agents releasable by ultrasound in cancer or other hyperproliferative tissue.