title: Polyethylene glycol-modified gelatin/polylactic acid nanoparticles for enhanced photodynamic efficacy of a hypocrellin derivative in vitro.
abstract: The present study focused on the development of a novel biodegradable nanoparticle system based on polyethyleneglycol-modified gelatin (PEG-GEL) and polylactic acid (PLA) biopolymers for improving the photodynamic efficacy of cyclohexane-1,2-diamino hypocrellin B (CHA2HB), a potent photodynamic therapeutic (PDT) agent. The CHA2HB-loaded PEG-GEL/PLA nanoparticles showed near-spherical morphology with an average size of 190 nm at a PLA to PEG-GEL ratio of 1:3. The drug loading was sufficient enough to produce potentially toxic reactive oxygen species (ROS) needed for photodynamic therapy (PDT). Slow and controlled drug release was observed in normal conditions, whereas enzyme assistance resulted in a relatively fast release due to partial disintegration of CHA2HB-loaded PEG-GEL/PLA nanoparticles. In vitro experiments indicated that CHA2HB-loaded PEG-GEL-PLA nanoparticles are efficiently taken up by cancer cells such as human breast adenocarcinoma (MCF-7), human gastric sarcoma (AGS) and mice specific Dalton's lymphoma (DLA) in a time dependent manner. Further, CHA2HB-loaded PEG-GEL/PLA nanoparticles evoked superior phototoxicity compared to free-CHA2HB towards all the three cell lines investigated. Interestingly, PDT effectiveness was different for the different cell type studied. CHA2HB-loaded PEG-GEL/PLA nanoparticles induced both apoptotic and necrotic cell death as a result of photoirradiation. Thus, our data suggest that PEG-GEL/PLA nanoparticles are highly effective in delivery and phototoxic enhancement of CHA2HB against model cancer cells in vitro.
authors.affiliation: School of Biological Sciences, Madurai Kamaraj University, Madurai 625021, India.
authors.forename: Anish
authors.initials: A
authors.lastname: Babu
authors.forename: Jayaprakash
authors.initials: J
authors.lastname: Periasamy
authors.forename: Amsaveni
authors.initials: A
authors.lastname: Gunasekaran
authors.forename: Ganesan
authors.initials: G
authors.lastname: Kumaresan
authors.forename: Selvaraj
authors.initials: S
authors.lastname: Naicker
authors.forename: Paramasamy
authors.initials: P
authors.lastname: Gunasekaran
authors.forename: Ramachandran
authors.initials: R
authors.lastname: Murugesan
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005780:Gelatin / Q000737:chemistry*; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D018625:Microscopy, Atomic Force; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D010569:Perylene / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D038761:Photobleaching; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology; D011091:Polyesters; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D011809:Quinones / Q000494:pharmacology* / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D016896:Treatment Outcome
chemical_list: D017319:Photosensitizing Agents; D011091:Polyesters; D011108:Polymers; D011809:Quinones; D017382:Reactive Oxygen Species; D019344:Lactic Acid; D011092:Polyethylene Glycols; C033616:poly(lactide); D010569:Perylene; D005780:Gelatin; C064522:hypocrellin B