title: Extra cellular pH influences uptake and photodynamic action of pyropheophorbide-a entrapped in folate receptor targeted organically modified silica nanoparticle.
abstract: BACKGROUND
  Photodynamic efficacy of pyropheophorbide-a (PPa) is limited due to poor aqueous solubility. In the present study, organically modified silica nanoparticles (ORMOSIL) entrapping PPa and its folate receptor targeted conjugate (FR-Np-PPa) were prepared and the effect of pH on uptake and photodynamic action of plain and FR-Np-PPa in squamous cell carcinoma (Nt-8e) cells and adenocarcinoma of breast (MCF-7) cells were studied.
  
  
  METHODS
  Nanoformulations of PPa were characterized by absorption and fluorescence spectroscopy. Dynamic light scattering was used for size measurements. The uptake of the two nanoformulations by cells incubated in media of pH 6.5 and 7.4 was studied by confocal fluorescence microscopy and spectrofluoremetrically. Phototoxicity of PPa was studied by MTT assay.
  
  
  RESULTS
  In MCF-7 and Nt-8e cells, while the uptake of PPa was observed to increase with a decrease in pH of the incubation media for folate receptor targeted Np, uptake of Np-PPa was not influenced by a change in the pH of the media. Inhibition in the uptake of PPa in presence of free folic acid for cells incubated in a medium of pH 6.5 with targeted nanoparticles was higher compared to physiological pH. Consistent with uptake studies in both the cell lines phototoxicity of PPa delivered through FR-Np-PPa was higher in medium of pH 6.5 as compared to physiological pH and phototoxicity induced by NP-PPa was independent of the pH of medium.
  
  
  CONCLUSIONS
  Acidic pH enhances the photodynamic efficacy of FR-targeted nanoformulated PPa.
authors.affiliation: Laser Biomedical Applications and Instrumentation Division, Raja Ramanna Centre for Advanced Technology, Indore 452013, India.
authors.forename: Surya Prakash
authors.initials: SP
authors.lastname: Singh
authors.affiliation: Laser Biomedical Applications and Instrumentation Division, Raja Ramanna Centre for Advanced Technology, Indore 452013, India. Electronic address: msharma@rrcat.gov.in.
authors.forename: Mrinalini
authors.initials: M
authors.lastname: Sharma
authors.affiliation: Laser Biomedical Applications and Instrumentation Division, Raja Ramanna Centre for Advanced Technology, Indore 452013, India.
authors.forename: Harishankar
authors.initials: H
authors.lastname: Patel
authors.affiliation: Laser Biomedical Applications and Instrumentation Division, Raja Ramanna Centre for Advanced Technology, Indore 452013, India.
authors.forename: Pradeep Kumar
authors.initials: PK
authors.lastname: Gupta
mesh_terms: D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002734:Chlorophyll / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D045604:Extracellular Fluid / Q000737:chemistry* / Q000187:drug effects / Q000528:radiation effects; D058972:Folic Acid Transporters / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D061986:MCF-7 Cells; D008657:Metabolic Clearance Rate / Q000187:drug effects / Q000528:radiation effects; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D009374:Neoplasms, Experimental / Q000737:chemistry* / Q000188:drug therapy / Q000378:metabolism*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D012822:Silicon Dioxide / Q000737:chemistry; D016896:Treatment Outcome
chemical_list: D058972:Folic Acid Transporters; D053769:Nanocapsules; D011838:Radiation-Sensitizing Agents; D002734:Chlorophyll; C040298:pyropheophorbide a; D012822:Silicon Dioxide
keywords: Folate receptor; Organically modified silica nanoparticle; Photodynamic therapy; Pyropheophorbide-a