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Efficient Tumor and Mitochondria Uptake of 177Lu-Porphyrin-PEG Nanocomplexes for Multimodal Imaging Guided Combination Therapy

The benefits of intracellular drug delivery from nanomedicine has been limited by biological barriers and to some extent targeting capability. We investigated a size-controlled, dual tumormitochondria-targeted theranostic nanoplatform (Porphyrin-PEG Nanocomplexes, PPNs). The maximum tumor accumulation (15.6 %ID/g, 72 h p.i.) and ideal tumor-to-muscle ratio (16.6, 72 h p.i.) was achieved using an optimized PPN particle size of approximately 10 nm via PET imaging tracing. The stable coordination of PPNs with 177Lu enables integration of fluorescence imaging (FL) and photodynamic therapy (PDT) with positron emission tomography (PET) imaging and internal radiotherapy (RT). Furthermore, efficient tumor and mitochondrial uptake of 177Lu-PPNs greatly enhanced the efficacies of RT and/or PDT. This work developed a facile approach to fabricate tumor-targeted multi-modal nanotheranostic agents, which enables precision and radionuclide-based combination tumor therapy.