Endosomal pH-responsive micellar nanoparticles are prepared from an amphiphilic PEG-Schiff-DOX prodrug by the solution self-assembly. These nanoparticles have one outstanding advantage they can be stable in water for about 1 week if common conditions are provided. However, in a faintly acidic environment, it is unstable and easily disassembled. The concentration of DOX in the nanoparticle solutions could reach a high level of 265 μg/mL, along with an enormous drug loading capacity of 41.7%. The increase of intracellular DOX contents and the extension of circulation time are benefits of a pH-triggered drug release mechanism. CCK-8 found that these prepared nanoparticles possessed better antitumor ability than that of the free DOX against the Hela cells. These nanoparticles are expected to become a new DOX-supported dosage form for tumor research.

Heng Lu. pH-responsive prodrug nanoparticles for anti-tumor drug delivery. International Journal of Frontiers in Medicine (2024), Vol. 6, Issue 3: 10-15. https://doi.org/10.25236/IJFM.2024.060302.

[1] Ulbrich, K., Hola, K., Subr, V., Bakandritsos, A., Tucek, J., & Zboril, R. (2016). Targeted drug delivery with polymers and magnetic nanoparticles: covalent and noncovalent approaches, release control, and clinical studies. Chemical reviews, 116(9), 5338-5431.

[2] Ge, Z., Liu S. (2013). Functional block copolymer assemblies responsive to tumor and intracellular microenvironments for site-specific drug delivery and enhanced imaging performance. Chem. Soc. Rev. 42, 7289-7325.

[3] Wei, H., Zhuo, R.X., Zhang, X.Z. (2013). Design and development of polymeric micelles with cleavable links for intracellular drug delivery. Prog. Polym. Sci. 38, 503-535.

[4] Kemp, J.A., Shim, M.S., Heo, C.Y., Kwon Y.J. (2016). “Combo” nanomedicine: Co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy. Adv. Drug Deliv. Rev. 98, 3-18.

[5] Fan, X., Li, Z., Xian, J.L. (2016). Recent development of unimolecular micelles as functional materials and applications. Polym. Chem., 7, 5898-5919.

[6] Sun, Q., Radosz, M., Shen, Y. (2012). Challenges in design of translational nanocarriers. J. Control. Release 164, 156-169.

[7] Cabral, H., Matsumoto, Y., Mizuno, K., Chen, Q., Murakami, M., Kimura, M., Terada, Y., Kano, M.R., Miyazono, K., Uesaka, M., Nishiyama, N., Kataoka, K. (2011). Accumulation of sub-100 nm polymeric micelles in poorly permeable tumours depends on size. Nat. Nanotechnol. 6 815-823.

[8] Liow, S.S., Dou, Q., Kai, D., Li, Z., Sugiarto, S., Yu, C.Y.Y., Kwok, R.T.K., Chen, X., Wu, Y.L., Ong, S.T., Kizhakeyil, A., Verma, N.K., Tang, B.Z., Loh, X.J. (2017). Long-term real-time in vivo drug release monitoring with AIE thermogelling polymer. Small 13, 1603404.

[9] Loh, X.J., Goh, S.H., Li, J. (2009). Biodegradable thermogelling poly [(R)-3-hydroxybutyrate]-based block copolymers: micellization, gelation, and cytotoxicity and cell culture studies. J. Phys. Chem. B 113, 11822-11830.

[10] Hwang, J.Y., Li, Z., Loh, X.J. (2016). Small molecule therapeutic-loaded liposomes as therapeutic carriers: from development to clinical applications. RSC Adv. 6, 70592-70615. 

[11] Li, D., Bu, Y., Zhang, L., Wang, X., Yang, Y., Zhuang, Y., Yang, F., Shen, H., Wu, D. (2016). Facile construction of pH- and redox-responsive micelles from a biodegradable poly(β-hydroxyl amine) for drug delivery. Biomacromolecules 17, 291-300.

[12] Liu, X., Chen, X., Chua, M.X., Li, Z., Loh, X.J., Wu, Y.L. (2017). Injectable supramolecular hydrogels as delivery agents of Bcl-2 conversion gene for the effective shrinkage of therapeutic resistance tumors. Adv. Healthc. Mater. 6, 1700159.

[13] Li, Z., Liu, X., Chen, X., Ming, X.C., Wu, Y.L. (2017). Targeted delivery of Bcl-2 conversion gene by MPEG-PCL-PEI-FA cationic copolymer to combat therapeutic resistant cancer. Mater. Sci. Eng. C 76, 66-72.

[14] Ding, C., Li, Z. (2017). A review of drug release mechanisms from nanocarrier systems. Mater. Sci. Eng. C 76, 1440-1453.

[15] Huang, P., Wang, D., Su, Y., Huang, W., Zhou, Y., Cui, D., Zhu, X., Yan, D. (2014). Combination of small molecule prodrug and nanodrug delivery: amphiphilic drug–drug conjugate for cancer therapy. J. Am. Chem. Soc. 136, 11748-11756.

[16] Shen, Y., Jin, E., Zhang, B., Murphy, C.J., Sui, M., Zhao, J., Wang, J., Tang, J., Fan, M., Van Kirk, E., Murdoch, W.J. (2010). Prodrugs forming high drug loading multifunctional nanocapsules for intracellular cancer drug delivery. J. Am. Chem. Soc. 132, 4259-4265.

[17] Yin, T., Wu, Q., Wang, L., Yin, L., Zhou, J., Huo, M. (2015). Well-defined redox-sensitive polyethene glycol–paclitaxel prodrug conjugate for tumor-specific delivery of paclitaxel using octreotide for tumor targeting. Mol. Pharmaceutics 12, 3020-3031.