Drug encapsulation into a nanoparticle enables improved pharmacokinetics, decreased toxicity and co-delivery of multiple drugs with contrast agents. Despite being widely explored, this approach has not been proven more efficacious in cancer treatment compared to free chemotherapy drugs, primarily due to low nanoparticle tumor uptake and poor tissue penetration. Photodynamic therapy (PDT) is an emerging therapeutic modality that employs a non-toxic light-sensitive drug (photosensitizer) in combination with light to produce reactive oxygen species and destroy nearby cancer cells. Several studies explored photodynamic pre-treatment as a way to enhance nanomedicine delivery to the tumor, but the utility and mechanism of this approach has not been fully realized.<br/>In our current work, we employed a low-molecular-weight (&lt;2 kDa) porphyrin photosensitizer targeting prostate-specific membrane antigen (Porphy-PSMA) in combination with sub-therapeutic near-infrared (NIR) laser irradiation to enhance tumor nanoparticle delivery. Presently, we have demonstrated that Porphy-PSMA-enabled PDT pre-treatment enhanced and accelerated accumulation of organic nanoparticles (100 nm liposomes and 20 nm lipoproteins) in PSMA-positive subcutaneous mouse model. Furthermore, this approach enhanced tumor delivery of 50 nm gold nanoparticles from 0.78 ± 0.46 %ID/g to 2.5 ± 0.27%ID/g at 3 hours post-nanoparticle administration, as demonstrated by inductively coupled plasma mass spectroscopy. We are currently investigating the effects of targeted PDT pre-treatment on nanoparticle intra-tumoral distribution via 3D imaging of optically transparent intact tumors as well as histological analysis.<br/>The low molecular weight of Porphy-PSMA allows it to homogeneously distribute within the tumor and its combination with targeted PDT opens access to the deep layers of tumor tissue for larger drug-carrying nanomedicines. This approach has a potential to enhance tumor accumulation and therapeutic efficacy of FDA-approved nanoformulations.

Enhancing nanoparticle delivery to the tumor with a targeted agent and light

256th National Meeting (2018)

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