Feasibility of poly(ethylene glycol) derivatives as diagnostic drug carriers for tumor imaging

Kanazaki, Kengo; Sano, Kohei; Makino, Akihiro; Yamauchi, Fumio; Takahashi, Atsushi; Homma, Tsutomu; Ono, Masahiro; Saji, Hideo

doi:10.1016/j.jconrel.2016.02.017

Cited by 32 publications

(42 citation statements)

References 35 publications

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“…As we previously reported, pharmacokinetics of PEG-ICG were changed by interaction between ICG and serum albumin 12 . Therefore, we measured the binding affinity ( K b value) of POZ-ICG (50 kDa, 5% hydrolysis).…”

Section: Discussionmentioning

confidence: 65%

“…Furthermore, multiple ICG molecules could not be conjugated to PEG, because only the terminal of polymer could be used to conjugate ( e.g. ICG/PEG = 1 in our previous study 12 ). To overcome this problem, we selected polyoxazoline (POZ) as a novel carrier of PA signal emitters.…”

mentioning

confidence: 98%

“…Because of its biocompatibility 9 , PA probes labeled with indocyanine green (ICG), a US Food and Drug Administration (FDA)-approved near-infrared fluorescence dye, have been investigated 10 . In our previous studies, the feasibility of using proteins and polyethylene glycol (PEG) conjugated with ICG for tumor-targeted PA probes has been demonstrated 11 12 13 . PEG with large molecular weight (>20 kDa) accumulated in the tumor via enhanced permeability and retention (EPR) effect 14 15 , and visualization of tumors was achieved in PA imaging.…”

mentioning

confidence: 99%

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Polyoxazoline multivalently conjugated with indocyanine green for sensitive in vivo photoacoustic imaging of tumors

Kanazaki

Sano

Makino

et al. 2016

Sci Rep

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Photoacoustic imaging, which enables high-resolution imaging in deep tissues, has lately attracted considerable attention. For tumor imaging, photoacoustic probes have been proposed to enhance the photoacoustic effect to improve detection sensitivity. Here, we evaluated the feasibility of using a biocompatible hydrophilic polymer, polyoxazoline, conjugated with indocyanine green (ICG) as a tumor-targeted photoacoustic probe via enhanced permeability and retention effect. ICG molecules were multivalently conjugated to partially hydrolyzed polyoxazoline, thereby serving as highly sensitive photoacoustic probes. Interestingly, loading multiple ICG molecules to polyoxazoline significantly enhanced photoacoustic signal intensity under the same ICG concentration. In vivo biodistribution studies using tumor bearing mice demonstrated that 5% hydrolyzed polyoxazoline (50 kDa) conjugated with ICG (ICG/polyoxazoline = 7.8), P14-ICG7.8, showed relatively high tumor accumulation (9.4%ID/g), resulting in delivery of the highest dose of ICG among the probes tested. P14-ICG7.8 enabled clear visualization of the tumor regions by photoacoustic imaging 24 h after administration; the photoacoustic signal increased in proportion with the injected dose. In addition, the signal intensity in blood vessels in the photoacoustic images did not show much change, which was attributed to the high tumor-to-blood ratios of P14-ICG7.8. These results suggest that polyoxazoline-ICG would serve as a robust probe for sensitive photoacoustic tumor imaging.

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Section: Discussionmentioning

confidence: 65%

mentioning

confidence: 98%

mentioning

confidence: 99%

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Polyoxazoline multivalently conjugated with indocyanine green for sensitive in vivo photoacoustic imaging of tumors

Kanazaki

Sano

Makino

et al. 2016

Sci Rep

Self Cite

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“…To address this issue, we develop a strategy to deliver the siRNA by MPA@siRNA@MC. The distribution of MPA@siRNA@MC in the body was observed by live body imaging [29][30][31]. As it is illustrated in Figure 5, free MPA mainly distributed to the liver, and then, its fluorescence signal decayed gradually mainly due to the clearance by kidney.…”

Section: Resultsmentioning

confidence: 98%

Near-infrared light-activatable siRNA delivery by microcapsules for combined tumour therapy

Rui

Pang

Zhang

et al. 2018

Artificial Cells, Nanomedicine, and Biotechnology

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A polyelectrolyte microcapsule-based layer-by-layer (LbL) technique has been widely used as a multifunctional vehicle for combined tumor therapy. Meanwhile, with the rapid development of combined tumour therapy, the challenge for designing multifunctional drug delivery system has attracted much more attention. Herein, we developed a new type of microcapsule (MC) system called MPA@siRNA@DOX@MC, which conjugated with siRNA and DOX as well as ICG-Der-02 (MPA) by electrostatic absorption. MPA as indocyanine green (ICG) fluorescence dye, exhibiting high fluorescence emission and photothermal conversion ability under NIR laser irradiation, was uploaded onto this drug system for realizing the controllable drug release and cancer theranostics. In addition, the results revealed that MPA@siRNA@DOX@MC possessed several ideal properties including high drug-loading capacity, excellent siRNA transfection efficiency, siRNA sequence protection and remarkably improved tumour-targeting capacity. Moreover, the combined therapy based on this drug system displayed improved therapeutic efficacy and negligible side effects both in vivo and in vitro experiment. Ultimately, MPA@siRNA@DOX@MC drug delivery system successfully combined the photothermal therapy and chemotherapy with controlled siRNA sequence silencing may have a promising potential in combined tumor therapy.

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“…Moreover, it is important to note that the size range is a compromise between the loading efficiency of liposomes (increases with increasing size), liposome stability (decreases with increasing size above an optimal 80-200 nm range), and ability for uptake in the tumors (decreases with increasing size). [20][21][22] PDI values of the formulations varied from 0.1 to 0.15, which means that the formulations were homogeneously dispersed. As for ζ-potential, it was more negative for SpHL-AL-DOX compared to SpHL-DOX (-12.4 mV vs -7.1 mV).…”

Section: Liposome Characterizationmentioning

confidence: 99%

Development of a bone-targeted pH-sensitive liposomal formulation containing doxorubicin: physicochemical characterization, cytotoxicity, and biodistribution evaluation in a mouse model of bone metastasis

Ferreira¹,

Faria²,

Lopes³

et al. 2016

IJN

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BackgroundDespite recent advances in cancer therapy, the treatment of bone tumors remains a major challenge. A possible underlying hypothesis, limitation, and unmet need may be the inability of therapeutics to penetrate into dense bone mineral, which can lead to poor efficacy and high toxicity, due to drug uptake in healthy organs. The development of nanostructured formulations with high affinity for bone could be an interesting approach to overcome these challenges.PurposeTo develop a liposomal formulation with high affinity for hydroxyapatite and the ability to release doxorubicin (DOX) in an acidic environment for future application as a tool for treatment of bone metastases.Materials and methodsLiposomes were prepared by thin-film lipid hydration, followed by extrusion and the sulfate gradient-encapsulation method. Liposomes were characterized by average diameter, ζ-potential, encapsulation percentage, X-ray diffraction, and differential scanning calorimetry. Release studies in buffer (pH 7.4 or 5), plasma, and serum, as well as hydroxyapatite-affinity in vitro analysis were performed. Cytotoxicity was evaluated by MTT assay against the MDA-MB-231 cell line, and biodistribution was assessed in bone metastasis-bearing animals.ResultsLiposomes presented suitable diameter (~170 nm), DOX encapsulation (~2 mg/mL), controlled release, and good plasma and serum stability. The existence of interactions between DOX and the lipid bilayer was proved through differential scanning calorimetry and small-angle X-ray scattering. DOX release was faster when the pH was in the range of a tumor than at physiological pH. The bone-targeted formulation showed a strong affinity for hydroxyapatite. The encapsulation of DOX did not interfere in its intrinsic cytotoxicity against the MDA-MB-231 cell line. Biodistribution studies demonstrated high affinity of this formulation for tumors and reduction of uptake in the heart.ConclusionThese results suggest that bone-targeted pH-sensitive liposomes containing DOX can be an interesting strategy for selectively delivering this drug into bone-tumor sites, increasing its activity, and reducing DOX-related toxicity.

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Feasibility of poly(ethylene glycol) derivatives as diagnostic drug carriers for tumor imaging

Cited by 32 publications

References 35 publications

Polyoxazoline multivalently conjugated with indocyanine green for sensitive in vivo photoacoustic imaging of tumors

Polyoxazoline multivalently conjugated with indocyanine green for sensitive in vivo photoacoustic imaging of tumors

Near-infrared light-activatable siRNA delivery by microcapsules for combined tumour therapy

Development of a bone-targeted pH-sensitive liposomal formulation containing doxorubicin: physicochemical characterization, cytotoxicity, and biodistribution evaluation in a mouse model of bone metastasis

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