Photosensitive Supramolecular Micelle-Mediated Cellular Uptake of Anticancer Drugs Enhances the Efficiency of Chemotherapy

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2020 Jul 8

PMID 32630069

Citations 3

Authors

Yihalem Abebe Alemayehu

Wen-Lu Fan

Fasih Bintang Ilhami

Chih-Wei Chiu

Duu-Jong Lee

Chih-Chia Cheng

Affiliations

Soon will be listed here.

Abstract

The development of stimuli-responsive supramolecular micelles with high drug-loading contents that specifically induce significant levels of apoptosis in cancer cells remains challenging. Herein, we report photosensitive uracil-functionalized supramolecular micelles that spontaneously form via self-assembly in aqueous solution, exhibit sensitive photo-responsive behavior, and effectively encapsulate anticancer drugs at high drug-loading contents. Cellular uptake analysis and double-staining flow cytometric assays confirmed the presence of photo-dimerized uracil groups within the irradiated micelles remarkably enhanced endocytic uptake of the micelles by cancer cells and subsequently led to higher levels of apoptotic cell death, and thus improved the therapeutic effect in vitro. Thus, photo-dimerized uracil-functionalized supramolecular micelles may potentially represent an intelligent nanovehicle to improve the safety, efficacy, and applicability of cancer chemotherapy, and could also enable the development of nucleobase-based supramolecular micelles for multifunctional biomaterials and novel biomedical applications.

Citing Articles

Synergistic effect of cold atmospheric plasma and methylene blue loaded nano micelles on treating human glioblastoma cells: An in vitro and molecular dynamics study.

Ahmadi E, Imanparast A, Hoseini M, Naseri S, Soudmand Salarabadi S, Sazgarnia A Iran J Basic Med Sci. 2025; 28(3):299-309.

PMID: 39906614 PMC: 11790199. DOI: 10.22038/ijbms.2024.79858.17304.

Development of Responsive Nanoparticles for Cancer Therapy.

Puiggali J Int J Mol Sci. 2023; 24(12).

PMID: 37373517 PMC: 10299338. DOI: 10.3390/ijms241210371.

Light-responsive polyurethanes: classification of light-responsive moieties, light-responsive reactions, and their applications.

Lam K, Lee C, Pichika M, Cheng S, Tan R RSC Adv. 2022; 12(24):15261-15283.

PMID: 35693222 PMC: 9118056. DOI: 10.1039/d2ra01506d.

Photo-Responsive Supramolecular Micelles for Controlled Drug Release and Improved Chemotherapy.

Ilhami F, Peng K, Chang Y, Alemayehu Y, Tsai H, Lai J Int J Mol Sci. 2020; 22(1).

PMID: 33375720 PMC: 7795671. DOI: 10.3390/ijms22010154.

References

Kaminskas L, McLeod V, Porter C, Boyd B . Association of chemotherapeutic drugs with dendrimer nanocarriers: an assessment of the merits of covalent conjugation compared to noncovalent encapsulation. Mol Pharm. 2012; 9(3):355-73. DOI: 10.1021/mp2005966. View

Mura S, Nicolas J, Couvreur P . Stimuli-responsive nanocarriers for drug delivery. Nat Mater. 2013; 12(11):991-1003. DOI: 10.1038/nmat3776. View

Chen W, Luo G, Lei Q, Jia H, Hong S, Wang Q . MMP-2 responsive polymeric micelles for cancer-targeted intracellular drug delivery. Chem Commun (Camb). 2014; 51(3):465-8. DOI: 10.1039/c4cc07563c. View

Mann J, Yu A, Agmon G, Appel E . Supramolecular polymeric biomaterials. Biomater Sci. 2017; 6(1):10-37. DOI: 10.1039/c7bm00780a. View

Deirram N, Zhang C, Kermaniyan S, Johnston A, Such G . pH-Responsive Polymer Nanoparticles for Drug Delivery. Macromol Rapid Commun. 2019; 40(10):e1800917. DOI: 10.1002/marc.201800917. View

Guo X, Wang L, Duval K, Fan J, Zhou S, Chen Z . Dimeric Drug Polymeric Micelles with Acid-Active Tumor Targeting and FRET-Traceable Drug Release. Adv Mater. 2017; 30(3). PMC: 6060406. DOI: 10.1002/adma.201705436. View

Stuart M, Huck W, Genzer J, Muller M, Ober C, Stamm M . Emerging applications of stimuli-responsive polymer materials. Nat Mater. 2010; 9(2):101-13. DOI: 10.1038/nmat2614. View

Rosenbaum I, Harnoy A, Tirosh E, Buzhor M, Segal M, Frid L . Encapsulation and covalent binding of molecular payload in enzymatically activated micellar nanocarriers. J Am Chem Soc. 2015; 137(6):2276-84. DOI: 10.1021/ja510085s. View

Adams M, Kwon G . Relative aggregation state and hemolytic activity of amphotericin B encapsulated by poly(ethylene oxide)-block-poly(N-hexyl-L-aspartamide)-acyl conjugate micelles: effects of acyl chain length. J Control Release. 2003; 87(1-3):23-32. DOI: 10.1016/s0168-3659(02)00347-4. View

10.

Allen T, Cullis P . Liposomal drug delivery systems: from concept to clinical applications. Adv Drug Deliv Rev. 2012; 65(1):36-48. DOI: 10.1016/j.addr.2012.09.037. View

11.

Madaan K, Kumar S, Poonia N, Lather V, Pandita D . Dendrimers in drug delivery and targeting: Drug-dendrimer interactions and toxicity issues. J Pharm Bioallied Sci. 2014; 6(3):139-50. PMC: 4097927. DOI: 10.4103/0975-7406.130965. View

12.

Liechty W, Kryscio D, Slaughter B, Peppas N . Polymers for drug delivery systems. Annu Rev Chem Biomol Eng. 2012; 1:149-73. PMC: 3438887. DOI: 10.1146/annurev-chembioeng-073009-100847. View

13.

Liang R, Wei M, Evans D, Duan X . Inorganic nanomaterials for bioimaging, targeted drug delivery and therapeutics. Chem Commun (Camb). 2014; 50(91):14071-81. DOI: 10.1039/c4cc03118k. View

14.

Ma X, Tian H . Stimuli-responsive supramolecular polymers in aqueous solution. Acc Chem Res. 2014; 47(7):1971-81. DOI: 10.1021/ar500033n. View

15.

Gulfam M, Matini T, Monteiro P, Riva R, Collins H, Spriggs K . Bioreducible cross-linked core polymer micelles enhance in vitro activity of methotrexate in breast cancer cells. Biomater Sci. 2017; 5(3):532-550. DOI: 10.1039/c6bm00888g. View

16.

Yu G, Yu W, Mao Z, Gao C, Huang F . A pillararene-based ternary drug-delivery system with photocontrolled anticancer drug release. Small. 2014; 11(8):919-25. DOI: 10.1002/smll.201402236. View

17.

Anselmo A, Mitragotri S . Nanoparticles in the clinic. Bioeng Transl Med. 2018; 1(1):10-29. PMC: 5689513. DOI: 10.1002/btm2.10003. View

18.

Cheng C, Chang F, Kao W, Hwang S, Liao L, Chang Y . Highly efficient drug delivery systems based on functional supramolecular polymers: In vitro evaluation. Acta Biomater. 2016; 33:194-202. DOI: 10.1016/j.actbio.2016.01.018. View

19.

Blanco E, Shen H, Ferrari M . Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat Biotechnol. 2015; 33(9):941-51. PMC: 4978509. DOI: 10.1038/nbt.3330. View

20.

Zhang Z, Lv Q, Gao X, Chen L, Cao Y, Yu S . pH-Responsive Poly(ethylene glycol)/Poly(L-lactide) Supramolecular Micelles Based on Host-Guest Interaction. ACS Appl Mater Interfaces. 2015; 7(16):8404-11. DOI: 10.1021/acsami.5b01213. View