Nanomedicines as photodynamic therapy for cancer

Photodynamic therapy (PDT) is an emerging treatment modality for cancer, especially for the treatment of superficial tumors, including melanoma, oesophagus and head and neck cancers. This is a low traumatic method for the... [ view full abstract ]

Photodynamic therapy (PDT) is an emerging treatment modality for cancer, especially for the treatment of superficial tumors, including melanoma, oesophagus and head and neck cancers. This is a low traumatic method for the treatment of oncological patients compared to surgery, which is gaining high recognition due to the moderate cost, absence of serious complications, and comparative selectivity of anticancer activity. PDT utilizes chemical photosensitizers (PSs), which produces reactive oxygen species (ROS) upon light irradiation at specific wavelengths, which kills target tumor tissues. Although PSs are highly effective in inducing apoptosis, and relatively non-toxic without irradiation, the poor hydrophobicity limits it therapeutic application. Therefore, effective delivery system for PSs is highly sought.

In our study, we have developed a nanomedicine, where a photosensitizer chlorin e6 (Ce6) had been loaded in a polymeric micellar system, poly(ethylene glycol)-poly(D,L-Lactide) (mPEG-PLA). After physico-chemical characterization, the cellular uptake and phototoxicity of Ce6-mPEG-PLA were evaluated compared to free Ce6 in Human lung adenocarcinoma cells (A549) in monolayer and in spheroid tumor model.

The micellar system was efficient in loaading Ce6 in the hydrophobic core as indicated by physico-chemical studies. Ce6-mPEG-PLA micelles showed high solubility and fluorescence intensity in aqueous media compared to free Ce6. Moreover, the ability of Ce6-mPEG-PLA to produce singlet oxygen, the primary inducer of apoptosis was assessed in aqueous media. Ce6-loaded mPEG-PLA micelles showed enhanced cellular uptake in A549 cells, decreased cell viability, and improved cellular internalization of the PS resulting in higher growth inhibition in avascular A549 spheroids compared to free drug.

In conclusion, Ce6 loaded mPEG-PLA micelles demonstrated significant cell killing ability in both monolayer and spheroid cultures compared to free Ce6. Considering that the mPEG-PLA nanocarrier is biocompatible, and biodegradable, this newly developed nano-formulation could have a great potential as clinical PDT for cancer.