Rational Design of Photoresponsive Anti-Cancer Drug Delivery Nanoparticles

Skin cancer is regarded as the most commonly diagnosed cancers especially in fair-skinnedhuman and pet populations worldwide today. Melanoma, a type of skin cancer,accounts for around 75% of skin cancer deaths in the U.S. Meanwhile, the incidence rateof melanoma among Caucasians has increased by 3 to 7% per year, especially in the U.S.More importantly, the World Health Organization (WHO) estimated that over 65thousand people per year worldwide would die from this malignant skin cancer.Undeniably, this malignancy poses tremendous burden on global healthcare system.Although surgery, radiotherapy and topical chemotherapy are in clinical practice, theyhave different degree of limitations and undesirable drawbacks. Chemotherapy is by farthe most prevailing treatment for skin cancer, but the successfulness of this approach isdependent on the dosage control: overdosing induces detrimental side effects whileunderdosing leads to relapse or exacerbation of patients’ conditions. Therefore, systemswhich allow controlled drug release are critical in improving drug efficacy and publicsafety.On the other hand, using light as an external trigger to control the release of drug fromtherapeutic carriers, technically known as photoresponsive drug delivery, is anticipatedto be a promising strategy for controlled drug release. More specifically, this technique isexpected to allow local, on-demand drug delivery with the merits of permitting a highconcentration of drug release at target sites while keeping the systemic concentration ofthe drug low, thereby reducing side effects due to bioaccumulation. Despite the meritshave been reported and photoliberation of small molecules from nano-therapeuticcarriers have been demonstrated, two key issues regarding the design of practicalphotoresponsive therapeutic carriers have not been addressed: (a) the therapeuticcarriers cannot utilize wavelengths which can penetrate deep into human skin, therebyhampering the phototriggering process; (b) high-power light source is required totrigger the drug release process due to the low quantum efficiency for thephotoliberation step, and such strong light source can bring damage to body tissue. Theobjectives of this proposal are to address these problems via rational design ofphotoresponsive drug delivery nanoparticles for melanoma. The success of this projectnot only can lead to a major technological breakthrough in cancer-related therapy, but itcan also provide an alternative strategy towards targeted therapies for other diseases.?