Abstract
Porphysomes (PS) are liposome-like nanoparticles comprising pyropheophorbide-conjugated phospholipids that have demonstrated potential as multimodal theranostic agents for applications that include phototherapies, targeted drug delivery and in vivo fluorescence, photoacoustic, magnetic resonance or positron emission imaging. Previous therapeutic applications focused primarily on photothermal therapy (PTT) and suggested that PSs require target-triggered activation for use as photodynamic therapy (PDT) sensitizers. Here, athymic nude mice bearing subcutaneous A549 human lung tumors were randomized into treatment and control groups: PS-PDT at various doses, PS-only and no treatment negative controls, as well as positive controls using the clinical photosensitizer Photofrin. Animals were followed for 30days post-treatment. PS-PDT at all doses demonstrated a significant tumor ablative effect, with the greatest effect seen with 10mg/kg PS at a drug-light interval of 24h. By comparison, negative controls (PS-only, Photofrin-only, and no treatment) showed uncontrolled tumor growth. PDT with Photofrin at 5mg/kg and PS at 10mg/kg demonstrated similar tumor growth suppression and complete tumor response rates (15 vs. 25%, p=0.52). Hence, porphysome nanoparticles are an effective PDT agent and have the additional advantages of multimodal diagnostic and therapeutic applications arising from their intrinsic structure. Porphysomes may also be the first single all-organic agent capable of concurrent PDT andPTT.
Highlights
Porphysomes (PSs) are nanoparticles (∼100 nm) composed of pyropheophorbide-conjugated phospholipid subunits that self-assemble into liposome-like structures, each containing ∼80,000 porphyrin molecules [1]
Athymic nude mice bearing subcutaneous A549 human lung tumors were randomized into treatment and control groups: PS-photodynamic therapy (PDT) at various doses, PS-only and no treatment negative controls, as well as positive controls using the clinical photosensitizer Photofrin
Previous studies have suggested that the PSs can be exploited in both their structurally intact state and in their disrupted state
Summary
Porphysomes (PSs) are nanoparticles (∼100 nm) composed of pyropheophorbide-conjugated phospholipid (pyro-lipid) subunits that self-assemble into liposome-like structures, each containing ∼80,000 porphyrin molecules [1]. They are preferentially taken up and retained in solid tumors via the enhanced permeability and retention (EPR) effect and subsequently taken up by cancer cells and disrupted into pyrolipid subunits [1]. Previous studies have suggested that the PSs can be exploited in both their structurally intact state (i.e., as nanoparticles) and in their disrupted state (i.e., as pyro-lipid subunits). The pyro-lipid subunits are unquenched, enabling fluorescence and photochemical reactions [2, 4, 7, 8]. These previous studies suggest that the conversion of PSs from their intact to their disrupted state is time dependent, though the relative populations of intact and disrupted PSs at any given time point are not well characterized
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