Photodynamic activity of viral nanoparticles conjugated with C-60
ABSTRACT The development of viral nanoparticles (VNP) displaying multiple copies of the buckyball (C(60)) and their photodynamic activity is described. VNP-C(60) conjugates were assembled using click chemistry. Cell uptake and cell killing using white light therapy and a prostate cancer cell line is demonstrated.
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ABSTRACT: Photodynamic therapy (PDT) is a promising treatment strategy where activation of photosensitizer drugs with specific wavelengths of light results in energy transfer cascades that ultimately yield cytotoxic reactive oxygen species which can render apoptotic and necrotic cell death. Without light the photosensitizer drugs are minimally toxic and the photoactivating light itself is non-ionizing. Therefore, harnessing this mechanism in tumors provides a safe and novel way to selectively eradicate tumor with reduced systemic toxicity and side effects on healthy tissues. For successful PDT of solid tumors, it is necessary to ensure tumor-selective delivery of the photosensitizers, as well as, the photoactivating light and to establish dosimetric correlation of light and drug parameters to PDT-induced tumor response. To this end, the nanomedicine approach provides a promising way towards enhanced control of photosensitizer biodistribution and tumor-selective delivery. In addition, refinement of nanoparticle designs can also allow incorporation of imaging agents, light delivery components and dosimetric components. This review aims at describing the current state-of-the-art regarding nanomedicine strategies in PDT, with a comprehensive narrative of the research that has been carried out in vitro and in vivo, with a discussion of the nanoformulation design aspects and a perspective on the promise and challenges of PDT regarding successful translation into clinical application.Journal of Controlled Release 03/2013; 168(1). DOI:10.1016/j.jconrel.2013.02.020 · 7.26 Impact Factor
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ABSTRACT: In this study, the synthesis of water-soluble fullerene derivatives bearing on one side a poly(amidoamine) (PAMAM) dendron with peripheral carboxylic groups and an alkyne moiety on the other side is presented. Fullerodendrimers with tert-butyl ester groups at the periphery were first prepared by treating C60 with unsymmetrical malonates through the use of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)/I2 or DBU/CBr4 conditions. The latter led to an unexpected addition of dibromocarbene on C60. The tert-butyl esters were then cleaved using formic acid and gave the corresponding carboxyfullerene derivatives. The second generation with eight carboxylic groups at the periphery was easily dissolved in water, whereas the first generation with its four carboxylic groups can only be solubilized in a basic medium. These compounds self-assemble into micelle-like aggregates probably composed of a cluster of C60 surrounded by a PAMAM shell. The alkyne moiety was then used as a chemical anchor to immobilize in water fullerodendrimers on the surface of azido-coated polymer nanoparticles by means of the copper(I)-catalyzed azide and alkyne cycloaddition reaction. At room temperature, this reaction is competing with azido cycloaddition onto the fullerene core. Given the high density of azide anchoring groups on the nanoparticle surface and the size of the fullerodendrimers, unreacted azides are still active and are available for subsequent functional arrangements. This strategy paves the way for the design of functional fullerene-rich nanomaterials that could be of interest in the field of materials science.ChemPlusChem 04/2013; 78(4). DOI:10.1002/cplu.201300045 · 3.24 Impact Factor
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ABSTRACT: Glycol chitosan (GC) grafted with 2,3-dimethylmaleic acid (DMA) and fullerene (C60) conjugates (GC-g-DMA-g-C60) were developed for use in a photosensitizer prodrug. GC-g-DMA-g-C60 was prepared via the simple two-step chemical grafting reactions of (i) DMA to free amine groups of GC and (ii) hydroxyl groups of GC-g-DMA to ππ carbon bonds of C60. This conjugate was self-assembled to form polysaccharidic nanogels consisting of a hydrophilic block (GC and DMA) and a hydrophobic block (C60). Here, GC-g-DMA-g-C60 nanogels also formed multi-nanogel aggregates due to the electrostatic interaction between the pendant carboxylic acid group (due to the DMA) and residual free amine group of GC at pH 7.4. Interestingly, the nanogel aggregates can be disintegrated at pH 5.0 due to the reduction of electrostatic interaction resulting from the cleavage of the DMA blocks at pH 5.0. Upon 670nm light illumination, photo-responsive properties of the nanogel aggregates allowed different singlet oxygen generation according to the pH condition: the reduced singlet oxygen generation (due to increased photo-interference effect between C60 molecules close-packed in nanogel aggregates) at pH 7.4, but the elevated singlet oxygen generation (due to the disintegration of nanogel aggregates) at pH 5.0. GC-g-DMA-g-C60 nanogel aggregates responds to pH 5.0 (∼endosomal pH) can be a good candidate for endosomal pH targeting and in vivo photodynamic therapy in various malignant tumor cells.01/2014; 101:692-8. DOI:10.1016/j.carbpol.2013.09.108