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.


BACKGROUND
Photodynamic 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.
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Alyssa M
AM
Master
Yizhi
Y
Qi
Nancy L
NL
Oleinick
Anirban Sen
AS
Gupta
D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology; D066246:ErbB Receptors / Q000737:chemistry / Q000378:metabolism; D005027:Ethylene Oxide / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D008823:Micelles; D058990:Molecular Targeted Therapy; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy; D010455:Peptides / Q000737:chemistry*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000737:chemistry / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000737:chemistry / Q000378:metabolism
D004337:Drug Carriers; C572557:GE11 peptide; D007783:Lactones; D008823:Micelles; C400421:PLC(20)-b-PEO(44); D010455:Peptides; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; C512478:EGFR protein, human; D066246:ErbB Receptors; D005027:Ethylene Oxide