Methylene Blue-containing Nanoparticle PlatformsT

This article presents the development and characterization of nanoparticles loaded with methylene blue (MB), which are designed to be administered to tumor cells externally and deliver singlet oxygen ('0,) for photodynamic therapy (PDT), i.e. cell kill via oxidative stress to the membrane. We demonstrated the encapsulation of MB, a photosensitizer (PS), in three types of sub-200 nm nanoparticles, composed of polyacrylamide, sol-gel silica and organically modified silicate (ORMOSIL), respectively. Induced by light irradiation, the entrapped MB generated lo2, and the produced lo2 was measured quantitatively with anthracene-9,lO-dipropionic acid, disodium salt, to compare the effects of different matrices on '0, delivery. Among these three different kinds of nanoparticles, the polyacrylamide nanoparticles showed the most efficient delivery of lo2, but its loading of MB was low. In contrast, the sol-gel nanoparticles had the best MB loading but the least efficient lo2 delivery. In addition to investigating the matrix effects, a preliminary in vitro PDT study using the MBloaded polyacrylamide nanoparticles was conducted on rat C6 glioma tumor cells with positive photodynamic results. The encapsulation of MB in nanoparticles should diminish the interaction of this PS with the biological milieu, thus facilitating its systemic administration. Furthermore, the concept of the drug-delivering nanoparticles has been extended to a new type of dynamic nanoplatform (DNP) that only delivers lo2. This DNP could also be used as a targeted multifunctional platform for combined diagnostics and therapy of cancer. YPosted on the website on 13 December 2004 *To whom correspondence should be addressed: Department of Chemistry, University of Michigan, 930 N. University Avenue, Ann Arbor, MI 48109-1055, USA. Fax: 734-936-2778; e-mail: [email protected] Abbreviations: ADPA, anthracene-9,lO-dipropionic acid, disodium salt: AM, acetoxymethyl ester; AOT, dioctyl sulfosuccinate; APS, ammonium persulfate; BIS, N , N'-methylenebis(acry1amide); Brij 30, polyoxyethlyene (4) lauryl ether; DNP, dynamic nanoplatfonn; FDA, Food and Drug Administration; LMB, leukomethylene blue; MB, rnethylene blue; MDR, multidrug resistance; MOPS, (3-(N-morpholino) propanesulfonic acid) sodium salt; MRI, magnetic resonance imaging; MTMS, methyltrimethyoxysilane; 'Oz, singlet oxygen; ORMOSIL, organically modified silicate; PDT, photodynamic therapy; PI, propidium iodide; PS, photosensitizer; PTMS, phenyltrirnethyoxysilane: SEM, scanning electron microscopy; TEMED, N,N,N',N'-tetramethylethylenediamine; TEOS, tetraethylorthosilicate.