Jump to main content
Jump to site search


The effective treatment of multi-drug resistant tumors with self-assembling alginate copolymers

Author affiliations

Abstract

Alginates of two different chain lengths were alkyne functionalized on the hydroxyl group, leaving all carboxylic groups intact. The two polymers were grafted with poly(oligo ethylene glycol methacrylate) (POEGMA) with terminal azides by copper catalyzed azide–alkyne coupling (CuAAC) yielding well-defined comb copolymers with different POEGMA to alginate ratios. The unfunctionalized carboxylic groups and POEGMA endowed self-assembly characteristics to the copolymer in the presence of CaCl2, which was then further exploited to encapsulate paclitaxel and doxorubicin at encapsulation efficiencies of up to 50%. Release kinetics of the encapsulated drugs were recorded over 7 days showing a higher rate of release for the copolymers with a smaller alginate backbone. HepG2 cells with the overexpression of p-glycoproteins/MDR-1 were established and the drug loaded polymer nanoparticles exhibited significantly higher cytotoxicity as compared to the drug alone, while the polymers alone exhibited non-toxicity. These cells were injected subcutaneously into Balb/C nude mice to establish a solid tumor model, to which intra-tumoral administration of the drug loaded nanoparticles showed a strong anti-tumor performance, particularly for the doxorubicin loaded particles which shrank the tumors almost completely, without any significant effect on the weight of the mice. These new materials demonstrate a conceptual advance in the synthesis of viable drug delivery vectors from natural materials. The low toxicity of the materials, coupled with the encapsulation efficiency and ability to overcome multi-drug resistance, makes them strong candidates for a range of pharmaceutical applications well beyond cancer therapy.

Graphical abstract: The effective treatment of multi-drug resistant tumors with self-assembling alginate copolymers

Back to tab navigation

Supplementary files

Publication details

The article was received on 27 Aug 2018, accepted on 14 Nov 2018 and first published on 17 Nov 2018


Article type: Paper
DOI: 10.1039/C8PY01255E
Citation: Polym. Chem., 2019, Advance Article
  •   Request permissions

    The effective treatment of multi-drug resistant tumors with self-assembling alginate copolymers

    J. N. Kumar, Y. Wu, X. J. Loh, N. Y. Ho, S. X. Aik and V. Y. Pang, Polym. Chem., 2019, Advance Article , DOI: 10.1039/C8PY01255E

Search articles by author

Spotlight

Advertisements