Tuning the architecture of polymeric conjugate to mediate intracellular delivery of pleiotropic curcumin

Wang, Zheng; Chen, Chao; Zhang, Qi; Gao, Min; Zhang, Ju; Kong, Deling; Zhao, Yanjun

doi:10.1016/j.ejpb.2014.11.002

Cited by 61 publications

(50 citation statements)

References 35 publications

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“…Higher loading of Cur on GP was achieved as compared to other recently reported delivery cargos2425262728293031 (Supplementary Table S3). Even by utilizing GO, only 208 wt.% was obtained24 achieving only half of the loading capacity as compared to our current approach.…”

Section: Resultsmentioning

confidence: 75%

Exceedingly Higher co-loading of Curcumin and Paclitaxel onto Polymer-functionalized Reduced Graphene Oxide for Highly Potent Synergistic Anticancer Treatment

Muthoosamy

Abubakar²,

Bai

et al. 2016

Sci Rep

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Metastasis of lung carcinoma to breast and vice versa accounts for one of the vast majority of cancer deaths. Synergistic treatments are proven to be the effective method to inhibit malignant cell proliferation. It is highly advantageous to use the minimum amount of a potent toxic drug, such as paclitaxel (Ptx) in ng/ml together with a natural and safe anticancer drug, curcumin (Cur) to reduce the systemic toxicity. However, both Cur and Ptx suffer from poor bioavailability. Herein, a drug delivery cargo was engineered by functionalizing reduced graphene oxide (G) with an amphiphilic polymer, PF-127 (P) by hydrophobic assembly. The drugs were loaded via pi-pi interactions, resulting in a nano-sized GP-Cur-Ptx of 140 nm. A remarkably high Cur loading of 678 wt.% was achieved, the highest thus far compared to any other Cur nanoformulations. Based on cell proliferation assay, GP-Cur-Ptx is a synergistic treatment (CI < 1) and is highly potent towards lung, A549 (IC50 = 13.24 μg/ml) and breast, MDA-MB-231 (IC50 = 1.450 μg/ml) cancer cells. These positive findings are further confirmed by increased reactive oxygen species, mitochondrial membrane potential depletion and cell apoptosis. The same dose treated on normal MRC-5 cells shows that the system is biocompatible and cancerous cell-specific.

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Section: Resultsmentioning

confidence: 75%

Exceedingly Higher co-loading of Curcumin and Paclitaxel onto Polymer-functionalized Reduced Graphene Oxide for Highly Potent Synergistic Anticancer Treatment

Muthoosamy

Abubakar²,

Bai

et al. 2016

Sci Rep

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“…22 The proton NMR peak area integration gave a molecular weight (M n ) of 3,612 Da for mPEG-PLA, and 1,630 Da for TPGS, individually. 21 The lower CMC of PHEMA-(D NO ) 107 -(TPGS) 46 compared to its counterpart was due to the presence of more TPGS pendant as well as the ultrahigh hydrophobicity of tocopherol (Log P = 12.2). For PHEMA (20,000 Da), the backbone offered an average 153 hydroxyl group per polymer, enabling multivalent attachment functional moieties and therapeutic groups.…”

Section: Resultsmentioning

confidence: 99%

“…21 In brief, the graft copolymer PHEMA-(D NO ) 121 -(mPEG-PLA) 32 or PHEMA-(D NO ) 107 -(TPGS) 46 solution in DMF (0.1 g/mL, 10 mL) was sealed in a regenerated cellulose membrane (MWCO= 7,000 Da) and dialyzed against 1,000 mL distilled water to remove the organic solvent and drive the self-assembly of copolymers. 21 In brief, the graft copolymer PHEMA-(D NO ) 121 -(mPEG-PLA) 32 or PHEMA-(D NO ) 107 -(TPGS) 46 solution in DMF (0.1 g/mL, 10 mL) was sealed in a regenerated cellulose membrane (MWCO= 7,000 Da) and dialyzed against 1,000 mL distilled water to remove the organic solvent and drive the self-assembly of copolymers.…”

Section: Micelle Preparationmentioning

confidence: 99%

“…16,17 Although NO-releasing micellar nanocarriers have been shown able to mimic endogenous NO production, the meticulous control of NO spatiotemporal delivery is still challenging. 21 The aims of this study were to generate different amphiphilic polymeric micelles with multivalent NO donor conjugation and investigate the influence of polymer architecture on NO release. 19 The approach of monovalent chemical conjugating NO donor with carriers shows relatively poor loading.…”

Section: Introductionmentioning

confidence: 99%

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Nitric oxide-releasing graft polymer micelles with distinct pendant amphiphiles

et al. 2015

Self Cite

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Polymeric micelle is a versatile nanoscale platform for sustained release of short-lived nitric oxide (NO). The aim of this work was to better understand the correlation between polymer architecture and NO release kinetics. Stable nitrate was selected as the NO donor and co-conjugated to a multivalent polymer backbone together with amphiphilic methoxy poly(ethylene glycol) and poly(lactic acid) (mPEG-PLA), or D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS). Both graft polymers could self-assemble into micellar nanocarriers with a size less than 100 nm. The weight-based NO loading was 4.92% (w/w) and 6.05% (w/w) for mPEG-PLA-and TPGS-modified micelles, respectively. The former is less stable than the later with a corresponding critical micelle concentration of 23.9 ± 2.0 nM and 9.8 ± 0.5 nM. Using the standard Griess assay, it was shown that both micelles could achieve sustained NO release in vitro. However, the TPGS-modified nanocarrier exhibited a delayed onset, but faster steady-state release of NO in comparison to its counterpart. This was primarily due to folded PEG conformation and its high packing surface density. These results illustrate the potential utility of polymer architecture engineering to precisely tune the NO release behavior for ultimately optimum therapeutic outcome.

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“…2 Owing to its high potency as well as severe side effects, many targeted delivery systems have been designed in the past decade that include polymer based drug delivery systems. [10][11][12] Furthermore pH degradable cross-linked polymer nanostructures are advantageous as they retain their structural integrity even in dilute solutions unlike uncrosslinked nanostructures that are likely to disintegrate on dilution when injected into the body, thereby releasing the payload in unwanted places. We have also reported a polymer tethered magnetic nanoparticle system as a potent targeted delivery system for DOX.…”

Section: Introductionmentioning

confidence: 99%

pH-degradable and thermoresponsive water-soluble core cross-linked polymeric nanoparticles as potential drug delivery vehicle for doxorubicin

et al. 2015

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Controlled and efficient delivery of therapeutics to tumor cells is one of the key issues in cancer therapy. In the present work, a new class of water soluble polymeric core cross-linked nanoparticles (CLPNs) possessing acid degradable core and thermoresponsive shell was synthesized for pH-triggered delivery of drug to cancerous cell. The diol groups of poly(ethylene glycol)-b-poly(N-isopropylacrylamide)-b-poly(glycidyl methacrylate) diol triblock copolymer were utilized to form the core cross-linked polymeric nanoparticles through arm-first method by reaction with aldehyde functionalized cross-linkers through formation of acetal linkages. The encapsulation efficiency as well as the release properties of these CLPNs was investigated using doxorubicin (DOX), a known anticancer drug. The release was found to be preferable at the desired lysosomal pH (~5.0) of the cancer cells and below the LCST (~32 °C) of poly(Nisopropylacrylamide) (PNIPA). The cytotoxicities of the precursor polymer as well as the CLPNs were tested on the growth NIH/3T3, normal mouse fibroblast cells, and were found to be nontoxic. The anticancer activity of the DOX loaded CLPN was confirmed using cervical cancer cell lines HeLa and SiHa by MTT assay, morphological studies and flow cytometry. These studies revealed an increased accumulation of the drug around the nucleus when treated with DOX-loaded CLPN as compared to free DOX along with significant reduction in IC50 of both the cell lines. Thus, these CLPNs are potentially useful for controlled drug delivery in case of advanced chemotherapeutic applications.

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Tuning the architecture of polymeric conjugate to mediate intracellular delivery of pleiotropic curcumin

Cited by 61 publications

References 35 publications

Exceedingly Higher co-loading of Curcumin and Paclitaxel onto Polymer-functionalized Reduced Graphene Oxide for Highly Potent Synergistic Anticancer Treatment

Exceedingly Higher co-loading of Curcumin and Paclitaxel onto Polymer-functionalized Reduced Graphene Oxide for Highly Potent Synergistic Anticancer Treatment

Nitric oxide-releasing graft polymer micelles with distinct pendant amphiphiles

pH-degradable and thermoresponsive water-soluble core cross-linked polymeric nanoparticles as potential drug delivery vehicle for doxorubicin

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