EGFR-mediated intracellular delivery of Pc 4 nanoformulation for targeted photodynamic therapy of cancer: in vitro studies

In photodynamic therapy (PDT), the light activation of a photosensitizer leads to the generation of reactive oxygen species that can trigger various mechanisms of cell death. Harnessing this process within cancer cells enables minimally invasive yet targeted cancer treatment. With this rationale, here we demonstrate tumor-targeted delivery of a highly hydrophobic photosensitizer Pc 4 loaded within biocompatible poly(ethylene glycol)–poly(ɛ-caprolactone) block co-polymer micelles. The micelles were surface-modified with epidermal growth factor receptor (EGFR)–targeting GE11 peptides for active targeting of EGFR-overexpressing cancer cells, in vitro. Pc 4–loaded EGFR-targeted micelles were incubated with EGFR-overexpressing A431 epidermoid carcinoma cells for various time periods, to determine Pc 4 uptake by epifluorescence microscopy. The cells were subsequently photoirradiated, and PDT-induced cell death for various incubation periods was determined by MTT assay and fluorescence Live/Dead assay. Our results indicate that active EGFR targeting of the Pc 4–loaded micelles accelerates intracellular uptake of the drug. Consequently, this enhances the PDT-induced cytotoxicity within shorter time periods.From the Clinical EditorPhotodynamic cancer therapy using Pc 4, a light activated and highly hydrophobic photosensitizer is demonstrated in this paper in vitro. Pc 4 was delivered in block-copolymer micelles surface-modified with GE11 peptides targeting EGFR-overexpressing cancer cells.

Graphical AbstractPhotodynamic Therapy (PDT) has gained considerable clinical significance in the treatment of various cancerous and precancerous tissues. PDT efficacy partly depends on enhancing the selective accumulation of the photosensitizer (PS) within the tumor while minimizing its nonspecific uptake and reducing the risk of phototoxicity and photosensitivity in normal tissues. For this purpose, formulation of PS molecules in cancer-targeted nanovehicles can be highly effective. In the current study we investigate the targeting and PDT efficacy of a PS, namely Pc 4, formulated within block co-polymeric micellar nanovehicles surface-decorated with peptide ligands targeted to epidermal growth factor receptors (EGFRs). EGFR upregulation and activity is implicated in the growth and survival of a variety of cancers, and hence we envision that our targeted Pc 4 nanoformulation will enable EGFR-mediated cell-selective rapid uptake of the PS in these cancers, for enhanced PDT by subsequent photoirradiation.Figure optionsDownload high-quality image (206 K)Download as PowerPoint slide