Porphyrin nanovesicles have been developed that can release drugs in response to red laser irradiation, leading to enhanced drug deposition in irradiated tumors. Inclusion of 2 molar % porphyrin-phospholipid (PoP) imparts optimal near infrared (NIR) light-triggered release of doxorubicin (Dox) from conventional sterically stabilized stealth liposomes. Dox in stealth PoP liposomes has a circulation half-life in mice of 21.9 hours and is stable in storage for months. Following intravenous injection and NIR irradiation, Dox deposition increases ~7 fold in treated subcutaneous xenografts. A low dose 3 mg/kg Dox phototreatment with stealth PoP liposomes was more effective than a maximum tolerated dose of free (7 mg/kg) or conventional long-circulating liposomal Dox (21 mg/kg). These liposome are effective at physiologically relevant dosing of 2 mg/kg in orthotopic models of breast cancer in rodents.<br/> <br/>Second, these porphyrin nanovesicles can be chelated with cobalt for simple functionalization using polyhistidine ligands. Methods to attach polypeptides to lipid bilayers are often indirect, ineffective and can represent a substantial bottleneck in the formation of functionalized lipid-based materials. Although the polyhistidine tag (his-tag) has been transformative in its simplicity and efficacy in binding to immobilized metals, the successful application of this approach has been challenging in physiological settings. Here we show that lipid bilayers containing porphyin-phospholipid that is chelated with cobalt, but not other metals, can effectively capture his-tagged proteins and peptides. The binding follows a Co(II) to Co(III) transition and occurs within the sheltered hydrophobic bilayer, resulting in essentially irreversible attachment in serum or in million-fold excess of competing imidazole. Using this approach we anchored peptides and proteins into the liposome for spontaneous nanoliposome-antigen particleization (SNAP) adjuvants, which show 10,000 more potency than other adjuvants for a malaria antigen of interest.<br/>

Biomedical applications of porphyrin-phospholipid liposomes

256th National Meeting (2018)

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