New biodegradable bisphosphonate vinylic monomers and near infrared fluorescent nanoparticles for biomedical applications

Gluz, Eran; Rudnick-Glick, Safra; Mizrahi, Dana M.; Chen, Ravit; Margel, Shlomo

doi:10.1002/pat.3247

Cited by 7 publications

(12 citation statements)

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“…The nanoparticles introduce the use of fluorescence in the NIR region (700–1000 nm), where autofluoresence, light scattering and absorption of the light by normal tissues is not a concern. This way, the imaging has an improved signal-to-noise ratio, as the background is non-fluorescent in the NIR region and the detection of the fluorophore is optimal [ 7 ]–[ 9 ]. Nanoparticles containing NIR dyes have already been developed and proved to have significant advantages over free NIR dyes, including biocompatibility, improved fluorescence signal, enhanced photostability and the presence of functional groups on the nanoparticle surface allowing easy conjugation to bioactive molecules [ 6 ],[ 10 ]–[ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Engineering of near infrared fluorescent proteinoid-poly(L-lactic acid) particles for in vivo colon cancer detection

et al. 2014

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BackgroundThe use of near-infrared (NIR) fluorescence imaging techniques has gained great interest for early detection of cancer owing to the negligible absorption and autofluorescence of water and other intrinsic biomolecules in this region. The main aim of the present study is to synthesize and characterize novel NIR fluorescent nanoparticles based on proteinoid and PLLA for early detection of colon tumors.MethodsThe present study describes the synthesis of new proteinoid-PLLA copolymer and the preparation of NIR fluorescent nanoparticles for use in diagnostic detection of colon cancer. These fluorescent nanoparticles were prepared by a self-assembly process in the presence of the NIR dye indocyanine green (ICG), a FDA-approved NIR fluorescent dye. Anti-carcinoembryonic antigen antibody (anti-CEA), a specific tumor targeting ligand, was covalently conjugated to the P(EF-PLLA) nanoparticles through the surface carboxylate groups using the carbodiimide activation method.Results and discussionThe P(EF-PLLA) nanoparticles are stable in different conditions, no leakage of the encapsulated dye into PBS containing 4% HSA was detected. The encapsulation of the NIR fluorescent dye within the P(EF-PLLA) nanoparticles improves significantly the photostability of the dye. The fluorescent nanoparticles are non-toxic, and the biodistribution study in a mouse model showed they evacuate from the body over 24 h. Specific colon tumor detection in a chicken embryo model and a mouse model was demonstrated for anti-CEA-conjugated NIR fluorescent P(EF-PLLA) nanoparticles.ConclusionsThe results of this study suggest a significant advantage of NIR fluorescence imaging using NIR fluorescent P(EF-PLLA) nanoparticles over colonoscopy. In future work we plan to broaden this study by encapsulating cancer drugs such as paclitaxel and/or doxorubicin, within these biodegradable NIR fluorescent P(EF-PLLA) nanoparticles, for both detection and therapy of colon cancer.

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Section: Introductionmentioning

confidence: 99%

Engineering of near infrared fluorescent proteinoid-poly(L-lactic acid) particles for in vivo colon cancer detection

et al. 2014

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“…For therapeutic purposes doxorubicin was bound to the surface of the BP NPs through a PEG spacer, as described in the literature, per 1 mg of BP NPs 5 µg doxorubicin was conjugated [25]. The synthesis of both the BP NPs and the conjugation of doxorubicin are incredibly reproducible to that reported in the literature [25, 33]. Using the equation: [d = density (1 g/ml); g = mass (1 g); r = radius (cm)], we were able to calculate the number (n) of BP NPs per mg (0.5 × 10 12 particles), enabling us to determine the concentration of doxorubicin per BP NP as 1 × 10 −14 µg doxorubicin/NP.…”

Section: Resultsmentioning

confidence: 99%

“…1) [27]. These NPs were characterized using Dynamic light scattering and TEM and found to conform to those described in the literature [33]. The APMA monomer contains a primary amine group which allows for the covalent binding of a dye/drug to the surface of the particles as shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…1. For optical imaging of bone tumor targeting we attached the NIR dye Cy7 to the surface of these particles [25, 33]. For therapeutic purposes doxorubicin was bound to the surface of the BP NPs through a PEG spacer, as described in the literature, per 1 mg of BP NPs 5 µg doxorubicin was conjugated [25].…”

Section: Resultsmentioning

confidence: 99%

“…Using the equation: [d = density (1 g/ml); g = mass (1 g); r = radius (cm)], we were able to calculate the number (n) of BP NPs per mg (0.5 × 10 12 particles), enabling us to determine the concentration of doxorubicin per BP NP as 1 × 10 −14 µg doxorubicin/NP. These NPs, due to their high content of BP, when administered by IV to chicken embryo model have been shown to specifically target bone tumor [25, 27, 33].

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Section: Resultsmentioning

confidence: 99%

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Targeted drug delivery of near IR fluorescent doxorubicin-conjugated poly(ethylene glycol) bisphosphonate nanoparticles for diagnosis and therapy of primary and metastatic bone cancer in a mouse model

et al. 2016

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BackgroundMost primary and metastatic bone tumors demonstrate increased osteoclast activity and bone resorption. Current treatment is based on a combination of surgery, radiotherapy and chemotherapy. Severe side effects are associated with chemotherapy due to use of high dosage and nonspecific uptake. Bisphosphonates have a strong affinity to Ca2+ ions and are widely used in the treatment of bone disorders.ResultsWe have engineered a unique biodegradable bisphosphonate nanoparticle (NPs) bearing two functional surface groups: (1) primary amine groups for covalent attachment of a dye/drug (e.g. NIR dye Cy 7 or doxorubicin); (2) bisphosphonate groups for targeting and chelation to bone hydroxyapatite. In addition, these engineered NPs contain high polyethyleneglycol (PEG) concentration in order to increase their blood half life time. In vitro experiments on Saos-2 human osteosarcoma cell line, demonstrated that at a tenth of the concentration, doxorubicin-conjugated bisphosphonate NPs achieved a similar uptake to free doxorubicin. In vivo targeting experiments using the NIR fluorescence bisphosphonate NPs on both Soas-2 human osteosarcoma xenograft mouse model and orthotopic bone metastases mCherry-labeled 4T1 breast cancer mouse model confirmed specific targeting. In addition, therapeutic in vivo experiments using doxorubicin-conjugated bisphosphonate NPs demonstrated a 40% greater inhibition of tumor growth in Saos-2 human osteosarcoma xenograft mouse model when compared to free doxorubicin.ConclusionsIn this research we have shown the potential use of doxorubicin-conjugated BP NPs for the targeting and treatment of primary and metastatic bone tumors. The targeted delivery of doxorubicin to the tumor significantly increased the efficacy of the anti-cancer drug, thus enabling the effective use of a lower concentration of doxorubicin. Furthermore, the targeting ability of the BP NPs in an orthotopic xenograft mouse model reinforced our findings that these BP NPs have the potential to be used for the treatment of primary and metastatic bone cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12951-016-0233-6) contains supplementary material, which is available to authorized users.

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Black Phosphorus Quantum Dots Gated, Carbon‐Coated Fe₃O₄ Nanocapsules (BPQDs@ss‐Fe₃O₄@C) with Low Premature Release Could Enable Imaging‐Guided Cancer Combination Therapy

Zhang

Wang

et al. 2018

Chemistry A European J

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Combination therapies for tumors based on different therapeutic approaches should try to improve treatment efficacy, but also to reduce side-effects related to the exogenous stimulus and premature release. In the following study, we established and validated a pH/near-infrared (NIR)/glutathione (GSH)/-responsive multifunctional disulfide cross-linked Fe O @C nanocarriers (ss-Fe O @C NCs) with black phosphorus quantum dots (BPQDs) as a capping agent. BPQDs and carbon shell of Fe O @C nanoparticles (NPs) were used as a photothermal agents, while the inner empty nucleus that allows for a high drug payload served as an effective drug carrier. These magnetofluorescent BPQDs@DOX@ss-Fe O @C NPs were conjugated with a targeting aptamer (epidermal growth factor receptor: EGFR), denoted as BPQDs@DOX@ss-Fe O @C-EGFR NPs, for targeting dual modal magnetic resonance (MR)/fluorescence imaging. The synthetic NCs showed that drug release was dependent on pH, near-infrared (NIR), and intracellular GSH levels, with minimum systemic release in the blood and maximum drug release within the tumors. Also, the photothermal effect resulting from the Fe O @C NPs and BPQDs upon application to NIR light caused a rapid rise in local temperature, which accounted for the highest enhancement of cell cytotoxicity. Thus, a theranostic system consisting of BPQDs@DOX@ss-Fe O @C-EGFR NPs is shown to generate excellent advantages in combined chemotherapy/photothermal therapy (PTT) with minimal side effects.

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New biodegradable bisphosphonate vinylic monomers and near infrared fluorescent nanoparticles for biomedical applications

Cited by 7 publications

References 44 publications

Engineering of near infrared fluorescent proteinoid-poly(L-lactic acid) particles for in vivo colon cancer detection

Engineering of near infrared fluorescent proteinoid-poly(L-lactic acid) particles for in vivo colon cancer detection

Targeted drug delivery of near IR fluorescent doxorubicin-conjugated poly(ethylene glycol) bisphosphonate nanoparticles for diagnosis and therapy of primary and metastatic bone cancer in a mouse model

Black Phosphorus Quantum Dots Gated, Carbon‐Coated Fe₃O₄ Nanocapsules (BPQDs@ss‐Fe₃O₄@C) with Low Premature Release Could Enable Imaging‐Guided Cancer Combination Therapy

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New biodegradable bisphosphonate vinylic monomers and near infrared fluorescent nanoparticles for biomedical applications

Cited by 7 publications

References 44 publications

Engineering of near infrared fluorescent proteinoid-poly(L-lactic acid) particles for in vivo colon cancer detection

Engineering of near infrared fluorescent proteinoid-poly(L-lactic acid) particles for in vivo colon cancer detection

Targeted drug delivery of near IR fluorescent doxorubicin-conjugated poly(ethylene glycol) bisphosphonate nanoparticles for diagnosis and therapy of primary and metastatic bone cancer in a mouse model

Black Phosphorus Quantum Dots Gated, Carbon‐Coated Fe3O4 Nanocapsules (BPQDs@ss‐Fe3O4@C) with Low Premature Release Could Enable Imaging‐Guided Cancer Combination Therapy

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Black Phosphorus Quantum Dots Gated, Carbon‐Coated Fe₃O₄ Nanocapsules (BPQDs@ss‐Fe₃O₄@C) with Low Premature Release Could Enable Imaging‐Guided Cancer Combination Therapy