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Curcumin-loaded redox response of self-assembled micelles for enhanced antitumor and anti-inflammation efficacy.

ABSTRACT: At present, it has become evident that inflammation plays a critical role in tumor growth; meanwhile, chemotherapeutic agents using nanocarriers have been suggested as a promising strategy in cancer treatment. In this study, novel redox-responsive micelles were prepared from monomethoxy-poly(ethylene glycol)-chitosan-S-S-hexadecyl (C₁₆-SS-CS-mPEG). These micelles were able to carry and deliver drugs into tumor cells. To serve as a control, monomethoxy-poly(ethylene glycol)-chitosan-C-C-hexadecyl (C₁₆-CC-CS-mPEG) was developed in a similar fashion to that used to yield C₁₆-CC-CS-mPEG without a redox-responsive disulfide bond. The cellular uptake mechanisms of both micelles were determined. The efficient intracellular drug release from micelles in MCF-7 cells was further confirmed. Results indicated that curcumin (Cur) could rapidly form C₁₆-SS-CS-mPEG@ Cur micelles when exposed to reducing agents and efficaciously enhance intracellular accumulation. The cytotoxicity assay demonstrated that C₁₆-SS-CS-mPEG@Cur exhibited satisfactory cytotoxicity against MCF-7 cells. Anti-inflammation assay results indicated that C₁₆-SS-CS-mPEG@Cur treatment significantly downregulated tumor necrosis factor (TNF-α) expression and showed good anti-inflammatory effects in tumor microenvironment. Most importantly, antitumor effects in vivo showed satisfactory therapeutic effects with C₁₆-SS-CS-mPEG@Cur. Hence, C₁₆-SS-CS-mPEG@Cur micelles can be useful in tumor therapy.

SUBMITTER: Zhao S

PROVIDER: S-EPMC5383081 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Curcumin-loaded redox response of self-assembled micelles for enhanced antitumor and anti-inflammation efficacy.

Zhao Shuang S Ma Litao L Cao Chengwen C Yu Qianqian Q Chen Lanmei L Liu Jie J

International journal of nanomedicine 20170329

At present, it has become evident that inflammation plays a critical role in tumor growth; meanwhile, chemotherapeutic agents using nanocarriers have been suggested as a promising strategy in cancer treatment. In this study, novel redox-responsive micelles were prepared from monomethoxy-poly(ethylene glycol)-chitosan-S-S-hexadecyl (C<sub>16</sub>-SS-CS-mPEG). These micelles were able to carry and deliver drugs into tumor cells. To serve as a control, monomethoxy-poly(ethylene glycol)-chitosan-C- ...[more]

PMID: 28408820

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Project description:Nano-micelles are self-assembling colloidal dispersions applied to enhance the anticancer efficacy of chemotherapeutic agents. In this study, the conjugate of quarternized chitosan and vanillin imine (QCS-Vani imine) was synthesized using the reaction of a Schiff base characterized by proton-NMR (1HNMR), UV-Vis spectroscopy, and FT-IR. The critical micelle concentration (CMC), particle size, and zeta potential of the resulting product were determined. The QCS-Vani imine conjugate was used as a carrier for the development of curcumin-loaded nano-micelles, and their entrapment efficiency (%EE), drug-loading capacity (%LC) and in vitro release were investigated using HPLC analysis. Moreover, the nano-micelles containing curcumin were combined with various concentrations of cisplatin and evaluated for a possible anticancer synergistic effect. The anticancer activity was evaluated against lung cancer A549 and mouse fibroblast L929 cell lines. The percent yield (%) of the QCS-Vani imine conjugate was 93.18%. The curcumin-loaded QCS-Vani imine nano-micelles were characterized and found to have a spherical shape (by TEM) with size < 200 nm (by DLS) with high %EE up to 67.61% and %LC up to 6.15 ± 0.41%. The loaded lyophilized powder of the nano-micelles was more stable at 4 °C than at room temperature during 120 days of storage. pH-sensitive release properties were observed to have a higher curcumin release at pH 5.5 (cancer environment) than at pH 7.4 (systemic environment). Curcumin-loaded QCS-Vani imine nano-micelles showed higher cytotoxicity and selectivity toward lung cancer A549 cell lines and exhibited lower toxicity toward the normal cell (H9C2) than pure curcumin. Moreover, the curcumin-loaded QCS-Vani imine nano-micelles exhibited an enhanced property of inducing cell cycle arrest during the S-phase against A549 cells and showed prominently induced apoptosis in lung cancer cells compared to that with curcumin. The co-treatment of cisplatin with curcumin-loaded QCS-Vani imine nano-micelles presented an enhanced anticancer effect, showing 8.66 ± 0.88 μM as the IC50 value, in comparison to the treatment with cisplatin alone (14.22 ± 1.01 μM). These findings suggest that the developed QCS-Vani imine nano-micelle is a potential drug delivery system and could be a promising approach for treating lung cancer in combination with cisplatin.

Dataset Information

Curcumin-loaded redox response of self-assembled micelles for enhanced antitumor and anti-inflammation efficacy.

Publications

Curcumin-loaded redox response of self-assembled micelles for enhanced antitumor and anti-inflammation efficacy.

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