Preparation and characterization of novel poly(ethylene glycol) paclitaxel derivatives

Berlier, Gloria; Stella, Barbara; Schiavon, Oddone; Milla, Paola; Zonari, Daniele; Cattel, Luigi

doi:10.1016/j.ijpharm.2013.05.027

Cited by 11 publications

(9 citation statements)

References 34 publications

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“…1,2 Therefore, polymers are widely used as responsive coatings of surfaces for selective ion-permeability, 3 surface patterning 4,5 and drug delivery with polyplexes, 1,6,7 hybrid dendrimers, 8,9 and other drug-polymer conjugates. 10,11 Regarding drug-polymer conjugates, which offer relatively small particle sizes and good biocompatibility, possible issues may arise from low loading capacities and potentially poor stability, depending on the strength of the drug-polymer interactions. 12,13 The drug-polymer interactions need to be optimized for different kinds of drugs to ensure stable drug-polymer conjugates.…”

Section: Introductionmentioning

confidence: 99%

Multifunctional polymer-capped mesoporous silica nanoparticles for pH-responsive targeted drug delivery

et al. 2015

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A highly stable modular platform, based on the sequential covalent attachment of different functionalities to the surface of core-shell mesoporous silica nanoparticles (MSNs) for targeted drug delivery is presented. A reversible pH-responsive cap system based on covalently attached poly(2-vinylpyridine) (PVP) was developed as drug release mechanism. Our platform offers (i) tuneable interactions and release kinetics with the cargo drug in the mesopores based on chemically orthogonal core-shell design, (ii) an extremely robust and reversible closure and release mechanism based on endosomal acidification of the covalently attached PVP polymer block, (iii) high colloidal stability due to a covalently coupled PEG shell, and (iv) the ability to covalently attach a wide variety of dyes, targeting ligands and other functionalities at the outer periphery of the PEG shell. The functionality of the system was demonstrated in several cell studies, showing pH-triggered release in the endosome, light-triggered endosomal escape with an on-board photosensitizer, and efficient folic acid-based cell targeting.

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Section: Introductionmentioning

confidence: 99%

Multifunctional polymer-capped mesoporous silica nanoparticles for pH-responsive targeted drug delivery

et al. 2015

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“…PTXL-NHS was synthesized by slightly modifying a protocol reported in the literature . The as-synthesized PTXL-SA (60 mg, 0.063 mmol, 1.0 equiv) was dissolved in 10 mL of DCM in a 50 mL dried flask under a continuous flow of N 2 (g).…”

Section: Methodsmentioning

confidence: 99%

“…PTXL-NHS was synthesized by slightly modifying a protocol reported in the literature. 83 The as-synthesized PTXL-SA (60 mg, 0.063 mmol, 1.0 equiv) was dissolved in 10 mL of DCM in a 50 mL dried flask under a continuous flow of N 2 (g). Subsequently, NHS (9.59 mg, 0.083 mmol, 1.32 molar equiv according to PTXL-SA) and DCC (15.2 mg, 0.07 mmol, 1.11 molar equiv according to PTXL-SA) were added to the same flask.…”

Section: ■ Conclusionmentioning

confidence: 99%

Reduction-Sensitive Dextran–Paclitaxel Polymer–Drug Conjugate: Synthesis, Self-Assembly into Nanoparticles, and In Vitro Anticancer Efficacy

et al. 2021

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Delivery systems that can encapsulate a precise amount of drug and offer a spatiotemporally controlled drug release are being actively sought for safe yet effective cancer therapy. Compared to polymer nanoparticle (NP)-based delivery systems that rely on physical drug encapsulation, NPs derived from stimuli-sensitive covalent polymer−drug conjugates (PDCs) have emerged as promising alternatives offering precise control over drug dosage and spatiotemporal drug release. Herein, we report a reduction-sensitive PDC "Dex-SS-PTXL" synthesized by conjugating dextran and paclitaxel (PTXL) through a disulfide bondbearing linker. The synthesized Dex-SS-PTXL PDC with a precise degree of substitution in terms of the percentage of repeat units of dextran covalently conjugated to PTXL (27 ± 0.6%) and the amount of drug carried by the PDC (39 ± 1.4 wt %) was found to self-assemble into spherical NPs with an average size of 110 ± 34 nm and a ζ-potential of −14.09 ± 8 mV. The reduction-sensitive Dex-SS-PTXL NPs were found to release PTXL exclusively in response to the reducing agent concentration reflective of the intracellular reducing environment of the tumor cells. Challenging BT-549 and MCF-7 cells with Dex-SS-PTXL NPs revealed significant cytotoxicity, while the IC 50 values and the mode of action (mitotic arrest) of Dex-SS-PTXL NPs were found to be comparable to those of free PTXL, highlighting the active nature of the intracellularly released drug. The developed PDC with its unique ability to self-assemble into NPs and stimuli-responsive drug release can enhance the success of the NP-based drug delivery systems during clinical translation.

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“…We chose the commonly used chemotherapy drug, paclitaxel (PTX), in this proof‐of‐concept experiment. 2′‐NHS‐Paclitaxel (PTX‐NHS) (Figure S13, Supporting Information) was synthesized and conjugated to GST‐MT‐3(Co 2+ ) to produce the conjugate GST‐MT‐3 (Co 2+ )‐PTX ( Figure A). GST‐MT‐3(Co 2+ ) and PTX were present in a ratio of ≈1:1 using high‐performance liquid chromatography (Figure S14, Supporting Information).…”

Section: Methodsmentioning

confidence: 99%

A Novel Self‐Assembled Mitochondria‐Targeting Protein Nanoparticle Acting as Theranostic Platform for Cancer

Zhu

et al. 2018

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Self‐assembled protein nanoparticles have attracted much attention in biomedicine because of their biocompatibility and biodegradability. Protein nanoparticles have become widely utilized as diagnostic or therapeutic agents for various cancers. However, there are no reports that protein nanoparticles can specifically target mitochondria. This targeting is desirable, since mitochondria are critical in the development of cancer cells. In this study, the discovery of a novel self‐assembled metal protein nanoparticle, designated GST‐MT‐3, is reported, which targets the mitochondria of cancer cells within 30 min in vitro and rapidly accumulates in tumors within 1 h in vivo. The nanoparticles chelate cobalt ions [GST‐MT‐3(Co2+)], which induces reactive oxygen species (ROS) production and reduces the mitochondrial membrane potential. These effects lead to antitumor activity in vivo. GST‐MT‐3(Co2+) with covalently conjugated paclitaxel synergistically suppress tumors and prolong survival. Importantly, the effective dosage of paclitaxel is 50‐fold lower than that utilized in standard chemotherapy (0.2 vs 10 mg kg−1). To the best of the authors' knowledge, GST‐MT‐3 is the first reported protein nanoparticle that targets mitochondria. It has the potential to be an excellent platform for combination therapies.

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Preparation and characterization of novel poly(ethylene glycol) paclitaxel derivatives

Cited by 11 publications

References 34 publications

Multifunctional polymer-capped mesoporous silica nanoparticles for pH-responsive targeted drug delivery

Multifunctional polymer-capped mesoporous silica nanoparticles for pH-responsive targeted drug delivery

Reduction-Sensitive Dextran–Paclitaxel Polymer–Drug Conjugate: Synthesis, Self-Assembly into Nanoparticles, and In Vitro Anticancer Efficacy

A Novel Self‐Assembled Mitochondria‐Targeting Protein Nanoparticle Acting as Theranostic Platform for Cancer

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