Tumor specificity and therapeutic efficacy of photosensitizer-encapsulated glycol chitosan-based nanoparticles in tumor-bearing mice

Lee, So Jin; Park, Kyeongsoon; Oh, Yu‐Kyoung; Kwon, Soon-Jung; Her, Songwook; Kim, In San; Choi, Kuiwon; Lee, Sung Jun; Kim, Ho-Young; Lee, Se Geun; Kim, Kwangmeyung; Kwon, Ick Chan

doi:10.1016/j.biomaterials.2009.01.058

Cited by 156 publications

(116 citation statements)

References 21 publications

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“…Even simple PEGylation of the core photosensitizer itself results in high cellular uptake and low aggregation in biological media [121]. Similarly, protoporphyrin IX glycol-chitosan nanoparticles were shown to be superior to the non-encapsulated material [122].…”

Section: Biodegradable Nanoparticlesmentioning

confidence: 99%

Nanodrug applications in photodynamic therapy

Paszko

Ehrhardt

Senge

et al. 2011

Photodiagnosis and Photodynamic Therapy

322

215

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SummaryPhotodynamic therapy (PDT) has developed over last century and is now becoming a more widely used medical tool having gained regulatory approval for the treatment of various diseases such as cancer and macular degeneration. It is a two-step technique in which delivery of a photosensitizing drug is followed by irradiation of light. Activated photosensitizers transfer energy to molecular oxygen which results in generation of reactive oxygen species which in turn cause cells apoptosis or necrosis. Although this modality has significantly improved quality of life and survival time for many cancer patients it still offers significant potential for further improvement. In addition to the development of new PDT drugs, the use of nanosized carriers for photosensitizers is a promising approach which might improve the efficiency of photodynamic activity and which can overcome many side effects associated with classic photodynamic therapy. This review aims at highlighting the different types of nanomedical approaches currently used in PDT and outlines future trends and limitations of nanodelivery of photosensitizers. PDT -photodynamic therapy; PGA -poly(glycolic acid); PGLA -poly(D,L-lactide-coglycolide); PLA -poly(lactic acid); PS -photosensitizer; PEG -polyethylene glycol; ALA  aminolevulinic acid; m-THPC  5,10,15,20-tetra-(m-hydroxyphenyl)chlorine; m-THPP  meso-tetra(p-hydroxyphenyl); PpIX  protoporphyrin; Hp  hematoporphyrin; Pc4  silicon phthalocyanine; Ig  immunoglobulin; Tf  transferrin; TfR  transferrin receptor; VEGF  vascular endothelial growth factor; EPR  enhanced permeability and retention effect; FRET  fluorescence resonance energy transfer; MRI  magnetic resonance imaging; RES  reticuloendothelial system; ROS  reactive oxygen species; NP  nanoparticle; ND -nanodiamonds; SNP  silica nanoparticle; AMD  age-related macular degeneration; CNV  choroidal neovascularization; PTT  photothermal therapy;

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Section: Biodegradable Nanoparticlesmentioning

confidence: 99%

Nanodrug applications in photodynamic therapy

Paszko

Ehrhardt

Senge

et al. 2011

Photodiagnosis and Photodynamic Therapy

322

215

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“…Hydrophobically modified glycol chitosan derivatives can form stable self-aggregated nanoparticles in biological media solutions and be used as carriers for hydrophobic drugs and genes. [12][13][14][15] In our previous studies, cholesterol-modified glycol chitosan (CHGC) conjugate was synthesized and formed aggregated micelles in an aqueous medium. 16 In addition, the doxorubicin (DOX)-loaded CHGC nanoparticles exhibited prolonged circulation in the blood and showed higher antitumor efficacy against S180 tumorbearing mice through an enhanced permeability and retention effect than free DOX.…”

Section: Introductionmentioning

confidence: 99%

Fabrication and characterization of nuclear localization signal-conjugated glycol chitosan micelles for improving the nuclear delivery of doxorubicin

Yu¹,

Xie²,

Zheng³

et al. 2012

IJN

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Background: Supramolecular micelles as drug-delivery vehicles are generally unable to enter the nucleus of nondividing cells. In the work reported here, nuclear localization signal (NLS)-modified polymeric micelles were studied with the aim of improving nuclear drug delivery. Methods: In this research, cholesterol-modified glycol chitosan (CHGC) was synthesized. NLSconjugated CHGC (NCHGC) was synthesized and characterized using proton nuclear magnetic resonance spectroscopy, dynamic light scattering, and fluorescence spectroscopy. Doxorubicin (DOX), an anticancer drug with an intracellular site of action in the nucleus, was chosen as a model drug. DOX-loaded micelles were prepared by an emulsion/solvent evaporation method. The cellular uptake of different DOX formulations was analyzed by flow cytometry and confocal laser scanning microscopy. The cytotoxicity of blank micelles, free DOX, and DOX-loaded micelles in vitro was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in HeLa and HepG2 cells. Results: The degree of substitution was 5.9 cholesterol and 3.8 NLS groups per 100 sugar residues of the NCHGC conjugate. The critical aggregation concentration of the NCHGC micelles in aqueous solution was 0.0209 mg/mL. The DOX-loaded NCHGC (DNCHGC) micelles were observed as being almost spherical in shape under transmission electron microscopy, and the size was determined as 248 nm by dynamic light scattering. The DOX-loading content of the DNCHGC micelles was 10.1%. The DOX-loaded micelles showed slow drug-release behavior within 72 hours in vitro. The DNCHGC micelles exhibited greater cellular uptake and higher amounts of DOX in the nuclei of HeLa cells than free DOX and DOX-loaded CHGC (DCHGC) micelles. The half maximal inhibitory concentration (IC 50 ) values of free DOX, DCHGC, and DNCHGC micelles against HepG2 cells were 4.063, 0.591, and 0.171 µg/mL, respectively. Moreover, the IC 50 values of free DOX (3.210 µg/mL) and the DCHGC micelles (1.413 µg/mL) against HeLa cells were nearly 6.96-and 3.07-fold (P , 0.01), respectively, higher than the IC 50 value of the DNCHGC micelles (0.461 µg/mL). Conclusion:The results of this study suggest that novel NCHGC micelles could be a potential carrier for nucleus-targeting delivery.

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“…Biodegradable polymeric nanocarrier namely chitosan nanoparticles(CNPs) having an advantage of incorporating the hydrophobic drug PpIX to its hydrophobic inner core showed an improved tumor specificity and therapeutic efficiency for photodynamic therapy compared to free PpIX [17]. Studies on photosensitizers like PpIX, Rose Bengal (RB) with PAMAM and PPI dendrimers in HeLa cell lines, and with cyclic peptides in human cervical cancer SiHa cell line [18] are revealed to be non-toxic by PEGylation on their surface and also had good photodynamic activity both in vitro and in vivo [19].…”

Section: Introductionmentioning

confidence: 99%