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BACKGROUND: Fluorescence-guided surgery (FGS) can improve extent of resection in gliomas. Tozuleristide (BLZ-100), a near-infrared imaging agent composed of the peptide chlorotoxin and a near-infrared fluorophore indocyanine green, is a candidate molecule for FGS of glioma and other tumor types OBJECTIVE: To perform a phase 1 dose-escalation study to characterize the safety, pharmacokinetics, and fluorescence imaging of tozuleristide in adults with suspected glioma METHODS: Patients received a single intravenous dose of tozuleristide 3 to 29 h before surgery. Fluorescence images of tumor and cavity in Situ before and after resection and of excised tissue ex Vivo were acquired, along with safety and pharmacokinetic measures RESULTS: A total of 17 subjects received doses between 3 and 30 mg. No dose-limiting toxicity was observed, and no reported adverse events were considered related to tozuleristide. At doses of 9 mg and above, the terminal serum half-life for tozuleristide was approximately 30 min. Fluorescence signal was detected in both high- and low-grade glial tumors, with high-grade tumors generally showing greater fluorescence intensity compared to lower grade tumors. In high-grade tumors, signal intensity increased with increased dose levels of tozuleristide, regardless of the time of dosing relative to surgery. CONCLUSION: These results support the safety of tozuleristide at doses up to 30 mg and suggest that tozuleristide imaging may be useful for FGS of gliomas. Refereed/Peer-reviewed

Non-melanoma skin cancers are among the most commonly diagnosed skin cancers in the world. Ultraviolet radiation is a primary carcinogen resulting in UV induced mutations, loss of activity in tumour suppressor genes and the over expression of oncogenes in keratinocytes resulting in the development of skin malignancies. With the continued rising rate of non-melanoma skin cancer, topical therapies have become an established treatment method for effective lesion clearance. Current topical therapies include 5-fluorouracil, imiquimod, diclofenac, ingenol mebutate and photodynamic therapy. With high lesion recurrence rates still presenting as an issue following topical treatment, lack of drug selectivity for cancer cells, severe side effects from topical agent use and patient non-compliance due to prolonged treatment periods, new novel topical therapies need to be explored and developed. New therapies must target and clear both subclinical and clinically presenting skin cancers by interrupting the molecular mechanisms that induce and sustain the proliferation of neoplastic cells. Piperlongumine and EBC-46 are two naturally occurring small molecules which have demonstrated effective induction of cancer cell death. Piperlongumine, an amide isolated from the pepper, Piper longum, has demonstrated cancer cell death selectivity yet has no impact on healthy rapidly dividing primary cells. EBC-46 is a diterpene ester isolated from the seed of the fruit, Fontainea picrosperma. EBC-46 induces rapid inflammation and necrosis resulting in tumour ablation following intra-lesional injection. The development of Piperlongumine and EBC-46, as new topical agents offers a unique opportunity to further explore and exploit these selective properties for a more efficient and targeted approach to topical non -melanoma skin cancer treatment. Refereed/Peer-reviewed

Foroderm is a new cutaneous delivery technology that uses high-aspect ratio, cylindrical silica microparticles, that are massaged into the skin using a 3D-printed microtextured applicator, in order to deliver payloads across the epidermis. Herein we show that this technology is effective for delivery of a non-adjuvanted, inactivated, whole-virus chikungunya virus vaccine in mice, with minimal post-vaccination skin reactions. A single topical Foroderm-based vaccination induced T cell, Th1 cytokine and antibody responses, which provided complete protection against viraemia and disease after challenge with chikungunya virus. Foroderm vaccination was shown to deliver fluorescent, virus-sized beads across the epidermis, with beads subsequently detected in draining lymph nodes. Foroderm vaccination also stimulated the egress of MHC II+ antigen presenting cells from the skin. Foroderm thus has potential as a simple, cheap, effective, generic, needle-free technology for topical delivery of vaccines. Refereed/Peer-reviewed