Zinc pthalocyanine‐loaded chitosan/mPEG‐PLA nanoparticles‐mediated photodynamic therapy for the treatment of cutaneous squamous cell carcinoma

Abstract

Zinc pthalocyanine (ZnPc) is a second-generation photodynamic therapy (PDT) sensitizer with sufficient PDT activity for squamous cell carcinoma (SCC). ZnPc is hydrophobic and insoluble in water, which creates hurdles in systemic administration and hence restricts its use in clinic. Here we have loaded ZnPc on chitosan/methoxy polyethylene glycol-polylactic acid (CPP) nanoparticles to form Z-CPP to enhance PDT efficacy. In vitro and in vivo studies were performed to see dark toxicity of the compounds ZnPc, CPP and Z-CPP. Then PDT was done and its growth inhibitory effect on SCC cells was evaluated. In addition, reactive oxygen species (ROS) formation and apoptosis of cancer cells following PDT were studied. The results showed that the tested compounds exhibit no dark toxicity and the effect of PDT was significantly better with Z-CPP when compared to free ZnPc (P < .05). Photoactivation of Z-CPP led to a dose-dependent growth inhibition of cancer cells of >50% at 1 μM to >80% at 10 μM concentration. Also Z-CPP-treated cells had highest number of apoptotic cells and produced more ROS compared to free ZnPc-treated cells (P < .05). Hence, this study suggests that Z-CPP is a suitable pharmaceutical compound to increase PDT efficacy.

Advances in Photodynamic Therapy Based on Nanotechnology and Its Application in Skin Cancer

“…Loaded ZnPcs on chitosan/methoxy polyethylene glycol-polylactic acid (CPP) was used to form NP-(Z-CPP), and the dark toxicity and efficacy of topical PDT in SCC was examined using in vivo and in vitro tests. The results demonstrated that the compounds exhibited no dark toxicity, and the efficacy of PDT was significantly better using Z-CPP than using free ZnPcs ( 82 ).…”

Recent Progress in Phthalocyanine-Polymeric Nanoparticle Delivery Systems for Cancer Photodynamic Therapy

“…In addition, Keyal et al [ 57 ] investigated whether ZnPc-loaded chitosan/mPEG-PLA NPs topically applied onto tumor surfaces could increase penetration of PS through the keratinized surface of nodular tumors. In vivo studies performed with cutaneous squamous cell carcinoma tumor-bearing mice demonstrated that ZnPc-loaded nanoparticles possessed superior tumor accumulation and lack of systemic cytotoxicity compared to free ZnPc, indicating that the encapsulation of PS into nanocarriers and their subsequent topical application may be a promising platform for the treatment of skin cancers using PDT.…”

Chitosan Nanoparticles Potentiate the in vitro and in vivo Effects of Curcumin and other Natural Compounds

“…In the microemulsion method, a surfactant is solubilized into an organic solvent, and then, a solution containing CS with acetic acid and glutaraldehyde is added to form NPs under mechanic stirring [57,58,59]. The CS/NPs can be applied in several administration routes, such as parenteral [60], oral [61], nasal, ocular [62], topical and transdermal [63], increasing the solubility and permeability of different therapeutic agents, ensuring higher bioavailability and maintenance of these compounds in the body [64].…”