Effective Skin Cancer Treatment by Topical Co-delivery of Curcumin and STAT3 siRNA Using Cationic Liposomes

Abstract

The aim of the present study was to evaluate the effectiveness of iontophoretic co-delivery of curcumin and anti-STAT3 siRNA using cationic liposomes against skin cancer. Curcumin was encapsulated in DOTAP-based cationic liposomes and then complexed with STAT3 siRNA. This nanocomplex was characterized for the average particle size, zeta-potential, and encapsulation efficiency. The cell viability studies in B16F10 mouse melanoma cells have shown that the co-delivery of curcumin and STAT3 siRNA significantly (p < 0.05) inhibited the cancer cell growth compared with either liposomal curcumin or STAT3 siRNA alone. The curcumin-loaded liposomes were able to penetrate up to a depth of 160 μm inside the skin after iontophoretic (0.47 mA/cm) application. The in vivo efficacy studies were performed in the mouse model of melanoma skin cancer. Co-administration of the curcumin and STAT3 siRNA using liposomes significantly (p < 0.05) inhibited the tumor progression as measured by tumor volume and tumor weight compared with either liposomal curcumin or STAT3 siRNA alone. Furthermore, the iontophoretic administration of curcumin-loaded liposome-siRNA complex showed similar effectiveness in inhibiting tumor progression and STAT3 protein suppression compared with intratumoral administration. Taken together, cationic liposomes can be utilized for topical iontophoretic co-delivery of small molecule and siRNA for effective treatment of skin diseases.

Current and future technological advances in transdermal gene delivery

“…The experimental results reveal that 42.2% and 49.6% of the DCs in lymph nodes and splenocytes respectively were both GFP and CD11c positive. In contrast, only 1.59% and [190,191] Iontophoresis + liposome STAT3 siRNA Porcine skin Skin cancer 2016, [181,192] Iontophoresis Besides combination of physical and chemical approaches for more effective gene delivery via skin, there is also a large scope for each method to be further optimized. So far, a lot of work has been focused on applying a technique such as microneedle arrays or gold nanoparticles to deliver drug and gene molecules via the skin, followed by systematic investigation of drug delivery and distribution profiles as well as therapeutic or immunological functions.…”

<p>Development, Characterization and Use of Liposomes as Amphipathic Transporters of Bioactive Compounds for Melanoma Treatment and Reduction of Skin Inflammation: A Review</p>

“…This study showed that cell uptake increases proportionally with incubation time. 95 Cell uptake was analyzed by Petrilli et al 96 with confocal microscopy and flow cytometry in cell lines A431 and B16F10 treated with liposomes and immunoliposomes loaded with 3,3′-dioctadecyloxacarbocyanine perchlorate. They showed that immunoliposomes are easier to capture by the cells than simple liposomes.…”

“…It was shown that liposomes loaded with both, curcumin and complex STAT3-small interfering RNA, injected into the melanoma tumor decreased tumor volume from 3225 ± 558 mm 3 to 1316 ± 419 mm 3 , and its weight from 4.61 ± 0.49 g to 1.59 ± 0.69 g. The iontophoretic application showed a decrease in the tumor volume and weight, 726 ± 128 mm 3 and 0.88 ± 0.10 g, respectively. 95 In terms of curcumin penetration, a study showed that after incubation of liposomes in the skin for 24 hours, 2% to 7% of curcumin was present in the dermis. 87 In the case of skin cancer treatment, immunoliposomes were loaded with 5-fluorouracil and cetuximab and applied to cancer cells A431.…”

Nanoparticles Targeting STATs in Cancer Therapy

“…Therefore, liposomes can serve as promising candidates for delivery of STAT proteins in the treatment of skin cancers [241]. It appears that curcumin- and STAT3 siRNA-loaded liposomes significantly down-regulate the expression of STAT3 protein leading to the inhibition of tumor invasion and a remarkable reduction in tumor weight and tumor volume [242].…”