Abstract
The present study investigates the effect of the length of the hydrophobic poly(D,L-lactide) block on the self-assembly behavior of amphiphilic poly(D,L-lactide)-b-poly(ethylene glycol) (P(D,L)LA-b-PEG5k) copolymers with a large variation in molecular weight of the hydrophobic block (ranging from 5 to 100 kDa). To evaluate the cytotoxic effect of oxaliplatin-loaded P(D,L)LA-b-PEG5k nanoparticles (OXA-NPs) prepared by the nanoprecipitation method, a half maximal inhibitory concentration (IC50) study was conducted in cancer cell lines (MCF7, HCT116, and A549). The assays revealed that the IC50 values for OXA-NPs in HCT116 (1.93 ± 0.08 nM) and A549 (2.84 ± 0.11 nM) were significantly lower than those of pure OXA (12.70 ± 1.14 and 29.30 ± 0.40 nM, respectively). Moreover, the results showed that normal fibroblasts treated with blank NPs exhibited no significant growth inhibition in the concentration range of 0.001–1 mg mL–1, indicating their high biocompatibility.
REFERENCES
Kang, H., Rho, S., Stiles, W.R., Hu, S., Baek, Y., Hwang, D.W., Kashiwagi, S., Kim, M.S., and Choi, H.S., Adv. Healthcare Mater., 2020, vol. 9, no. 1, p. e1901223. https://doi.org/10.1002/adhm.201901223
Graham, M.A., Lockwood, G.F., Greenslade, D., Brienza, S., Bayssas, M., and Gamelin, E., Clin. Cancer Res., 2000, vol. 6, no. 4, p. 1205.
Garcia-Pinel, B., Jabalera, Y., Ortiz, R., Cabeza, L., Jimenez-Lopez, C., Melguizo, C., and Prados, J., Pharmaceutics, 2020, vol. 12, no. 6, p. 589. https://doi.org/10.3390/pharmaceutics12060589
Cabral, H., Miyata, K., Osada, K., and Kataoka, K., Chem. Rev., 2018, vol. 118, no. 14, p. 6844. https://doi.org/10.1021/acs.chemrev.8b00199
Govender, T., Riley, T., Ehtezazi, T., Garnett, M.S., Stolnik, S., Illum, L., and Davis, S.S., Int. J. Pharm., 2000, vol. 199, no. 1, p. 95. https://doi.org/10.1016/S0378-5173(00)00375-6
Simonutti, R., Bertani, D., Marotta, R., Ferrario, S., Manzone, D., Mauri, M., Gregori, M., Orlando, A., and Masserini, M., Polymer, 2021, vol. 218, p. 123511. https://doi.org/10.1016/j.polymer.2021.123511
Kadina, Y.A., Razuvaeva, E.V., Streltsov, D.R., Sedush, N.G., Shtykova, E.V., Kulebyakina, A.I., Puchkov, A.A., Volkov, D.S., Nazarov, A.A., and Chvalun, S.N., Molecules, 2021, vol. 26, no. 3, p. 602. https://doi.org/10.3390/molecules26030602
Al-Allaf, T.A., Rashan, L.J., Ketler, G., Fiebig, H., and Al-Dujaili, A.H., Appl. Organomet. Chem., 2009, vol. 23, p. 173. https://doi.org/10.1002/aoc.1489
Maeda, H., J. Pers. Med., 2021, vol. 11, no. 3, p. 229. https://doi.org/10.3390/jpm11030229
Cabral, H., Matsumoto, Y., Mizuno, K., Chen, Q., Murakami, M., Kimura, M., Terada, Y., Kano, M.R., Miyazono, K., Uesaka, M., Nishiyama, N., and Kataoka, K., Nat. Nanotechnol., 2011, vol. 6, no. 12, p. 815. https://doi.org/10.1038/nnano.2011.166
Garofalo, C., Capuano, G., Sottile, R., Tallerico, R., Adami, R., Reverchon, E., Carbone, E., Izzo, L., and Pappalardo, D., Biomacromolecules, 2014, vol. 15, no. 1, p. 403. https://doi.org/10.1021/bm401812r
Patil, S., Sandberg, A., Heckert, E., Self, W., and Seal, S., Biomaterials, 2007, vol. 28, no. 31, p. 4600. https://doi.org/10.1016/j.biomaterials.2007.07.029
Phan, H., Minut, R.I., McCrorie, P., Vasey, C., Larder, R.R., Krumins, E., Marlow, M., Rahman, R., Alexander, C., Taresco, V., and Pearce, A.K., J. Polym. Sci., Part A: Polym. Chem., 2019, vol. 57, no. 17, p. 1801. https://doi.org/10.1002/pola.29451
Glova, A.D., Melnikova, S.D., Mercurieva, A.A., Larin, S.V., and Lyulin, S.V., Polymers, 2019, vol. 11, p. 2056. https://doi.org/10.3390/polym11122056
Glova, A.D., Falkovich, S.G., Dmitrienko, D.I., Lyulin, A.V., Larin, S.V., Nazarychev, V.M., Karttunen, M., and Lyulin, S.V., Macromolecules, 2018, vol. 51, p. 552. https://doi.org/10.1021/acs.macromol.7b01640
Iakimov, N.P., Zotkin, M.A., Dets, E.A., Abramchuk, S.S., Arutyunian, A.M., Grozdova, I.D., and Melik-Nubarov, N.S., Colloid Polym. Sci., 2021, vol. 299, p. 1543. https://doi.org/10.1007/s00396-021-04853-2
Liu, L.Yu., Seitsonen, J., Xu, W., and Lehto, V.-S., Chem.—Eur. J., 2022, vol. 28, p. e202200947.
Shutkov, I.A. and Okulova, Y.N., Int. J. Mol. Sci., 2021, vol. 22, no. 24, p. 13468. https://doi.org/10.3390/ijms222413468
ACKNOWLEDGMENTS
TEM and DLS measurements were performed in Resource Centers of the National Research Center “Kurchatov Institute.”
Funding
The research was supported by the Russian Science Foundation (project no. 18-73-10079-P).
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
The authors declare that they have no conflicts of interest.
Supplementary Information
Rights and permissions
About this article
Cite this article
Puchkova, Y., Sedush, N., Kuznetsova, E. et al. Self-Assembly Behavior and Cytotoxicity of PEG-b-PLA Nanoparticles for Improved Oxaliplatin Delivery: Effect of PLA Block Length. rev. and adv. in chem. 13, 152–159 (2023). https://doi.org/10.1134/S2634827623600056
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S2634827623600056