Curcumin polymers as anticancer conjugates

Tang, Huadong; Murphy, Caitlin J.; Zhang, Bo; Shen, Youqing; Kirk, Edward A. Van; Murdoch, William J.; Radosz, Maciej

doi:10.1016/j.biomaterials.2010.06.007

Cited by 186 publications

(127 citation statements)

References 48 publications

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“…Such polycurcumin conjugates have the advantages of defined, high drug loading within the polymer backbones, leading to improved curcumin stability and tailored water-solubility. [9] In this paper, Cur containing 2 hydroxyl groups each molecule is used as a model example to demonstrate our PAPI strategy.We envisaged that an amphiphilic biotin-PEG-b-poly(curcumin-dithiodipropionic acid) (Biotin-PEG-PCDA), consisting of a high molecular weight (MW) hydrophobic PCDA block and a long PEG block, would assemble into stable core-shell nanoparticles (NPs), resulting in greatly increased water-solubility and offering effective protection against recognition and uptake by the reticuloendothelial system, allowing for prolonged circulation and effective tumour targeted accumulation via the EPR effect. Moreover, the hydrophobic core made of PCDA should lead to high drug loading and providing effective protection for Cur against hydrolysis.…”

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confidence: 99%

“…Many efforts have been made to overcome Cur's poor water solubility and instability, such as physical incorporation or encapsulation of Cur within a nanoparticle, conjugation with hydrophilic compounds and copolymerization with hydrophilic monomers. [8][9][10] For example, the Shen's group has reported the first polycurcumins by condensation polymerization of curcumin with various hydrophilic PEGs. Such polycurcumin conjugates have the advantages of defined, high drug loading within the polymer backbones, leading to improved curcumin stability and tailored water-solubility.…”

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confidence: 99%

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confidence: 99%

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Intracellularly Degradable, Self‐Assembled Amphiphilic Block Copolycurcumin Nanoparticles for Efficient In Vivo Cancer Chemotherapy

Guo

Shen

et al. 2015

Adv Healthcare Materials

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Chemotherapy is widely used in various cancer treatments. However, current cancer chemotherapy has a major limitation: lacking of specific targeting ability. As a result, it kills both cancerous and healthy cells, causing severe adverse side-effects and toxicity to patients which limits the dose regime and allows tumour to gain resistance. One approach to address this problem is the development of nanoscale drug delivery systems (NDDSs) which can exploit characteristic properties of tumour, such as the enhanced permeation and retention (EPR) effect, [1] and over-expressed cell-surface receptors, [2] to achieve targeted delivery. [3] Despite significant research achievements, most of the current NDDSs, especially those in clinical trials or usage, e.g. drug encapsulated lipids vesicles or polymer micelles, [4] polymerdrug conjugates, and albumin-based nanoparticles, [5] mostly rely on passive targeting and generally lack the ability of active targeting. Moreover, drugs are mostly physically encapsulated or entrapped into the NDDSs, where drug release is mainly achieved via passive diffusion, making it difficult to achieve controlled release, a vital property for high therapeutic 2 efficacy. As a result, most of the drug payloads may have been released before reaching the target sites, leading to reduced therapeutic efficacy and causing adverse side-effects.Furthermore, most NDDSs also suffer from drawbacks such as low drug loading (e.g.antibody-drug conjugates) and/or burst release (e.g. micelles/liposomes). To date, none of the current NDDSs can satisfy all of the requirements of an "idea NDDS" outlined by Langer et al. [3a] To make best use of the advantages of current NDDSs (passive and active targeting delivery to tumour) and overcome their drawbacks (unnecessary and even harmful on-way drug release before entering tumour cells and/or only a small quantity of drugs together with the nano-carriers entering tumour cells) due to the physical incorporation or encapsulation of drugs in NDDSs, which often leads to uncontrolled drug release via diffusion, we take a new approach to prepare NDDSs which is based on so-called poly(active pharmaceutical ingredient) (PAPI) strategy where the APIs are incorporated into an intracellular cleavable polymer backbone (not physically incorporated in drug carriers) in combination with selfassembly characteristics of amphiphilic block copolymers. Here PAPI is defined as a polymer prepared by polycondensation of an API or its derivative having the same or similar bioactivity as a co-or sole-monomer. Considerable advantages here are that the physicalchemical properties of the PAPIs can be readily tailored by changing co-monomers or via chemical modifications. The PAPIs can be further made into various NDDSs where the API release can be controlled via stimuli triggered polymer degradation, overcoming the drawback of un-controlled, diffusion based drug release character commonly experienced in physically incorporated systems. In principle, any drug molecules/derivatives containi...

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Intracellularly Degradable, Self‐Assembled Amphiphilic Block Copolycurcumin Nanoparticles for Efficient In Vivo Cancer Chemotherapy

Guo

Shen

et al. 2015

Adv Healthcare Materials

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“…PCur was prepared by condensation polymerization reaction as previously described with minor modifications (Tang et al, 2010). 1.10 g Cur, 1.25 g 3,3…”

Section: Synthesis Of Peg-ss-curcumin (Pcur) Conjugatementioning

confidence: 99%

Orally delivered polycurcumin responsive to bacterial reduction for targeted therapy of inflammatory bowel disease

et al. 2017

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Inflammatory bowel disease (IBD) such as Crohn's disease and ulcerative colitis is a chronic autoimmune disease affecting nearly five million people worldwide. Among all drug delivery system, oral administration is the most preferable route for colon-specific targeting and the treatment of IBD. Herein, an amphiphilic curcumin polymer (PCur) composed of hydrophilic poly(ethylene glycol) (PEG) and hydrophobic curcumin (Cur) linked by disulfide bond was synthesized and characterized. The sufficient solubility, nano-scaled size and close to the neutral surface potential of PCur lead to preferential accumulation of the active drug in the inflamed regions of the gut. Moreover, PCur showed limited drug release and enhanced robustness under the physiological pH of the gastrointestinal tract (GIT), and a significantly elevated release was observed when responding to a bacterial reduction in the colon. Furthermore, cellular studies confirmed PCur had low cytotoxicity and increased transmembrane permeability, resulting in improved oral bioavailability evidenced by in vivo pharmacokinetics of rats. Finally, with DSS-induced murine model of IBD, we demonstrated that orally administered PCur ameliorated the inflammatory progression in the colon and could protect mice from IBD. In conclusion, it is illustrated that the developed PCur conjugate could potentially be employed as a colon-specific candidate for IBD treatment.

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“…Subsequently, the DAPI staining solution was removed and the cells were washed by PBS twice before coverslips were mounted on the slides by a drop of permount. 42 Images were obtained using a Nikon…”

Section: Cellular Uptake and Localization Of Micellesmentioning

confidence: 99%

pH-responsive dendritic polyrotaxane drug-polymer conjugates forming nanoparticles as efficient drug delivery system for cancer therapy

Kang

Zhang

et al. 2015

Polym. Chem.

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a Self-assembly of stimuli-responsive polymeric nanoparticles have attracted great attention in recent years due to their prospective biological applications. This paper developed a novel pH-sensitive amphiphilic dendritic polyrotaxane drug-polymer conjugate by covalently linking doxorubicin (DOX) and dendritic polyrotaxane via a pH-responsible hydrazone bond with 1.84 wt% (weight percent) of DOX. The drugpolymer conjugate was amphiphilic and could be self-assembled to micelles (PR-g-DOX micelles) in an aqueous solution. The globular morphology and compact micelles with a diameter of around 110 nm were observed by SEM and TEM. Moreover, the micelles showed a significantly faster DOX release at mildly acidic pH of 6.0 and 5.0 and almost no burst release at the physiological pH of 7.4. Notably, it was confirmed that this micelle could efficiently deliver DOX to the nuclei of the tumor cells, which led to a much greater cytotoxic effects in the A549 cancer cells than the parent DOX. In vivo results revealed better drug tolerability of PR-g-DOX micelles and a higher in vivo efficacy without any increase in the toxicity of the PR-g-DOX micelles. Furthermore, the maximum tolerated dose (MTD) results showed that PRg-DOX micelles showed an excellent safety profile with a two-fold higher MTD (10 mg kg −1 DOX) than that of free DOX (5 mg kg −1 DOX). We are convinced that the PR-g-DOX micelle has tremendous potentials for targeted cancer therapy.

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Curcumin polymers as anticancer conjugates

Cited by 186 publications

References 48 publications

Intracellularly Degradable, Self‐Assembled Amphiphilic Block Copolycurcumin Nanoparticles for Efficient In Vivo Cancer Chemotherapy

Intracellularly Degradable, Self‐Assembled Amphiphilic Block Copolycurcumin Nanoparticles for Efficient In Vivo Cancer Chemotherapy

Orally delivered polycurcumin responsive to bacterial reduction for targeted therapy of inflammatory bowel disease

pH-responsive dendritic polyrotaxane drug-polymer conjugates forming nanoparticles as efficient drug delivery system for cancer therapy

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