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A novel combination chemotherapic strategy by co-delivery of doxorubicin (DOX) and mitomycin C (MC) anti-cancers was reported using dual pH and temperature-responsive copolymer-modified liposomes to achieve superior therapeutic efficacy. The copolymer was prepared using temperature-responsive N-isopropylacrylamide and pH-responsive poly-acrylic acid monomers through reversible addition–fragmentation chain transfer polymerisation and revealed dual pH/temperature-dependent phase transitions proved by differential scanning colorimetric and cloud point measurements. With relatively high encapsulation efficiency of 81.2% for DOX and 77.3% for MC, the prepared polymer-modified responsive liposomes (PMRLs) have shown enhanced and controlled temperature/pH-dependent release profiles and significantly lower thermal dose thresholds with up to a 250-fold decrease at pH 7.4 and 1000-fold decrease at pH 5.5 compared to the traditional formulations. The temperature/pH-dependent release profile of the drugs was investigated in vitro and cytotoxicity of the carriers was evaluated using both normal and cancerous cell lines. It was found that the two drugs co-loaded PMRLs were revealed synergistic effects on cytotoxicity of the carriers against Michigan Cancer Foundation-7 breast cancer cells. The results revealed that by this combinational regimen, the prepared liposomes have the potential to dramatically decrease the risk of damage to healthy tissues normally caused by liposomal cancer therapy.
References
-
-
1)
-
20. Ta, T., Convertine, A.J., Reyes, C.R., et al: ‘Thermosensitive liposomes modified with poly(N-isopropylacrylamide-co-propylacrylic acid) copolymers for triggered release of doxorubicin’, Biomacromolecules, 2010, 11, (8), pp. 1915–1920 (doi: 10.1021/bm1004993).
-
2)
-
11. Wu, Y., Lv, S., Li, Y., et al: ‘Co-delivery of dual chemo-drugs with precisely controlled, high drug loading polymeric micelles for synergistic anti-cancer therapy’, Biomater. Sci., 2020, 8, (3), pp. 949–959 (doi: 10.1039/C9BM01662G).
-
3)
-
9. Pan, J., Rostamizadeh, K., Filipczak, N., et al: ‘Polymeric co-delivery systems in cancer treatment: an overview on component drugs’ dosage ratio effect’, Molecules, 2019, 24, (6), p. 1035 (doi: 10.3390/molecules24061035).
-
4)
-
21. Zhang, Q., Weber, C., Schubert, U.S., et al: ‘Thermoresponsive polymers with lower critical solution temperature: from fundamental aspects and measuring techniques to recommended turbidimetry conditions’, Mater. Horiz., 2017, 4, (2), pp. 109–116 (doi: 10.1039/C7MH00016B).
-
5)
-
1. Li, Y., He, D., Tu, J.-S., et al: ‘Comparative effect of wrapping solid gold nanoparticles and hollow gold nanoparticles with doxorubicin-loaded thermosensitive liposomes for cancer thermo-chemotherapy’, Nanoscale, 2018, 10, pp. 8628–8641 (doi: 10.1039/C7NR09083H).
-
6)
-
23. Sapareto, S.A., Dewey, W.C.: ‘Thermal dose determination in cancer therapy’, Int. J. Radiat. Oncol. Biol. Phys., 1984, 10, (6), pp. 787–800 (doi: 10.1016/0360-3016(84)90379-1).
-
7)
-
5. Yuba, E.: ‘Development of functional liposomes by modification of stimuli-responsive materials and their biomedical applications’, J. Mater. Chem. B, 2020, 8, (6), pp. 1093–1107 (doi: 10.1039/C9TB02470K).
-
8)
-
29. Jia, M., Li, Y., Yang, X., et al: ‘Development of both methotrexate and mitomycin C loaded PEGylated chitosan nanoparticles for targeted drug codelivery and synergistic anticancer effect’, ACS Appl. Mater. Interface, 2014, 6, (14), pp. 11413–11423 (doi: 10.1021/am501932s).
-
9)
-
2. Wang, M., Liu, Y., Zhang, X., et al: ‘Gold nanoshell coated thermo-pH dual responsive liposomes for resveratrol delivery and chemo-photothermal synergistic cancer therapy’, J. Mater. Chem. B, 2017, 5, (11), pp. 2161–2171 (doi: 10.1039/C7TB00258K).
-
10)
-
26. Pantusa, M., Bartucci, R., Marsh, D., et al: ‘Shifts in chain-melting transition temperature of liposomal membranes by polymer-grafted lipids’, Biochim. Biophys. Acta (BBA) – Biomembranes, 2003, 1614, (2), pp. 165–170 (doi: 10.1016/S0005-2736(03)00171-8).
-
11)
-
22. Wiśniewska, M., Urban, T., Grządka, E., et al: ‘Comparison of adsorption affinity of polyacrylic acid for surfaces of mixed silica-alumina’, Colloid Polym. Sci., 2014, 292, (3), pp. 699–705 (doi: 10.1007/s00396-013-3103-x).
-
12)
-
3. Singh, S.P., Alvi, S.B., Pemmaraju, D.B., et al: ‘NIR triggered liposome gold nanoparticles entrapping curcumin as in situ adjuvant for photothermal treatment of skin cancer’, Int. J. Biol. Macromol., 2018, 110, pp. 375–382 (doi: 10.1016/j.ijbiomac.2017.11.163).
-
13)
-
24. McDannold, N.J., King, R.L., Jolesz, F.A., et al: ‘Usefulness of MR imaging-derived thermometry and dosimetry in determining the threshold for tissue damage induced by thermal surgery in rabbits’, Radiology, 2000, 216, (2), pp. 517–523 (doi: 10.1148/radiology.216.2.r00au42517).
-
14)
-
16. McCormick, C.L., Lowe, A.B.: ‘Aqueous RAFT polymerization: recent developments in synthesis of functional water-soluble (co)polymers with controlled structures’, Acc. Chem. Res., 2004, 37, (5), pp. 312–325 (doi: 10.1021/ar0302484).
-
15)
-
10. VanDyke, D., Kyriacopulos, P., Yassini, B., et al: ‘Nanoparticle based combination treatments for targeting multiple hallmarks of cancer’, Int. J. Nano Studies Technol., 2016, Suppl 4, pp. 1–18.
-
16)
-
17. Yin, X., Hoffman, A.S., Stayton, P.S.: ‘Poly(N-isopropylacrylamide-co-propylacrylic acid) copolymers that respond sharply to temperature and pH’, Biomacromolecules, 2006, 7, (5), pp. 1381–1385 (doi: 10.1021/bm0507812).
-
17)
-
14. Golemis, E.A., Scheet, P., Beck, T.N., et al: ‘Molecular mechanisms of the preventable causes of cancer in the United States’, Gen. Dev., 2018, 32, (13-14), pp. 868–902 (doi: 10.1101/gad.314849.118).
-
18)
-
13. Zhang, R.X., Cai, P., Zhang, T., et al: ‘Polymer–lipid hybrid nanoparticles synchronize pharmacokinetics of co-encapsulated doxorubicin–mitomycin C and enable their spatiotemporal co-delivery and local bioavailability in breast tumor’, Nanomed. Nanotechnol. Biol. Med., 2016, 12, (5), pp. 1279–1290 (doi: 10.1016/j.nano.2015.12.383).
-
19)
-
27. Prasad, P., Shuhendler, A., Cai, P., et al: ‘Doxorubicin and mitomycin C co-loaded polymer-lipid hybrid nanoparticles inhibit growth of sensitive and multidrug resistant human mammary tumor xenografts’, Cancer Lett., 2013, 334, (2), pp. 263–273 (doi: 10.1016/j.canlet.2012.08.008).
-
20)
-
6. Muttaqien, S.E., Nomoto, T., Takemoto, H., et al: ‘Poly(N-isopropylacrylamide)-based polymer-inducing isothermal hydrophilic-to-hydrophobic phase transition via detachment of hydrophilic acid-labile moiety’, Biomacromolecules, 2019, 20, (4), pp. 1493–1504 (doi: 10.1021/acs.biomac.8b01465).
-
21)
-
8. Xia, T., Hao, W., Shang, Y., et al: ‘Incorporation of amphipathic diblock copolymer in lipid bilayer for improving pH responsiveness’, Int. J. Polym. Sci., 2016, 5, p. 10.
-
22)
-
18. Chiang, Y.-T., Lo, C.-L.: ‘pH-responsive polymer-liposomes for intracellular drug delivery and tumor extracellular matrix switched-on targeted cancer therapy’, Biomaterials, 2014, 35, (20), pp. 5414–5424 (doi: 10.1016/j.biomaterials.2014.03.046).
-
23)
-
25. Allen, T.M., Cullis, P.R.: ‘Drug delivery systems: entering the mainstream’, Science, 2004, 303, (5665), pp. 1818–1822 (doi: 10.1126/science.1095833).
-
24)
-
28. Cheung, R.Y., Rauth, A.M., Ronaldson, P.T., et al: ‘In vitro toxicity to breast cancer cells of microsphere-delivered mitomycin C and its combination with doxorubicin’, Eur. J. Pharm. Biopharm., 2006, 62, (3), pp. 321–331 (doi: 10.1016/j.ejpb.2005.09.011).
-
25)
-
19. Yuba, E.: ‘Design of pH-sensitive polymer-modified liposomes for antigen delivery and their application in cancer immunotherapy’, Polym. J., 2016, 48, p. 761 (doi: 10.1038/pj.2016.31).
-
26)
-
15. Zhang, R.X., Zhang, T., Chen, K., et al: ‘Sample extraction and simultaneous chromatographic quantitation of doxorubicin and mitomycin C following drug combination delivery in nanoparticles to tumor-bearing mice’, J. Visual. Exp., 2017, 128, p. 56159.
-
27)
-
4. Shiraishi, K., Yokoyama, M.: ‘Toxicity and immunogenicity concerns related to PEGylated-micelle carrier systems: a review’, Sci. Technol. Adv. Mater., 2019, 20, (1), pp. 324–336 (doi: 10.1080/14686996.2019.1590126).
-
28)
-
12. Villar-Alvarez, E., Cambón, A., Pardo, A., et al: ‘Combination of light-driven co-delivery of chemodrugs and plasmonic-induced heat for cancer therapeutics using hybrid protein nanocapsules’, J. Nanobiotechnol., 2019, 17, (1), p. 106 (doi: 10.1186/s12951-019-0538-3).
-
29)
-
7. Liang, Y., Kiick, K.L.: ‘Liposome-cross-linked hybrid hydrogels for glutathione-triggered delivery of multiple cargo molecules’, Biomacromolecules, 2016, 17, (2), pp. 601–614 (doi: 10.1021/acs.biomac.5b01541).
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