Poster Presentation Australasian Society for Dermatological Research Annual Scientific Meeting 2017

Engineer targeted melanin nanoparticles for skin cancer treatment (#39)

Nhung Dang 1 , Sam Osserian 2 , CONOR L Evans 2 , Tarl W Prow 1 3
  1. The University of Queensland, Woolloongabba, QLD, Australia
  2. Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MASSACHUSETTS, US
  3. Biomaterials Engineering and Nanomedicine Strand, Future Industries Institute, The University of South Austral, Adelaide, South Australia, Australia

The use of nanoparticles to target drug delivery has been widely explored in cancer treatment due to several advantages over conventional chemotherapy. Nanoparticles can carry chemotherapeutics directly to the tumour and protect drugs from being degraded before they reach their target. We hypothesize that melanin, a natural pigment nanoparticle, could be an effective drug delivery platform. We hypothesize that MMP-2 cleavable peptides can release therapeutic drugs into non-melanoma skin cancers among other cancers, where this protease is overexpressed. Therefore, we conjugated a MMP-2 cleavable peptide to melanin nanoparticles via streptavidin-biotin bonding to serve as enzyme-responsive nanosystem.

Nanoparticles were synthesized using synthetic melanin by changing pH environment and under ultrasonication. The resulting nanoparticles were covalently linked to streptavidin and attached to a MMP-2 cleavable peptide (containing a terminal FAM for imaging) via streptavidin–biotin. The particle sizes were determined using TEM and Zetasizer measurements. Nanoparticle uptake was evaluated using confocal microscopy and flow cytometry assay in vitro.

TEM imaging revealed particle sizes ranging from 4 to 60 nm. However, particle sizing was not reliable during Zetasiser measurement, likely due to interference from melanin’s scattering properties. The percentage of streptavidin conjugation varied from 51.28% to 98.78% depending on the ratio of melanin nanoparticles and streptavidin. Microscopy images show co-localized signals from melanin nanoparticles in sum-frequency absorption mode using CARS imaging and fluorescence from the peptide. Fluorescence uptake in a cancer cell line was observed with single photon microscopy and confirmed with flow cytometry.

Melanin nanoparticles conjugated with MMP-2 cleavable peptide synthesized and validated. The incorporation of MMP-2 cleavage domains in the nanoparticle-linked peptide has potential as a targeted skin cancer therapy where MMP-2 is overexpressed, like squamous cell carcinoma.

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