Recent Advances on Polymeric Beads or Hydrogels as Embolization Agents for Improved Transcatheter Arterial Chemoembolization (TACE)

Abstract

Transcatheter arterial chemoembolization (TACE), aiming to block the hepatic artery for inhibiting tumor blood supply, became a popular therapy for hepatocellular carcinoma (HCC) patients. Traditional TACE formulation of anticancer drug emulsion in ethiodized oil (i.e., Lipiodol^®) and gelatin sponge (i.e., Gelfoam^®) had drawbacks on patient tolerance and resulted in undesired systemic toxicity, which were both significantly improved by polymeric beads, microparticles, or hydrogels by taking advantage of the elegant design of biocompatible or biodegradable polymers, especially amphiphilic polymers or polymers with both hydrophilic and hydrophobic chains, which could self-assemble into proposed microspheres or hydrogels. In this review, we aimed to summarize recent advances on polymeric embolization beads or hydrogels as TACE agents, with emphasis on their material basis of polymer architectures, which are important but have not yet been comprehensively summarized.

Keywords: TACE; cancer therapy; drug delivery; hydrogel; polymeric beads.

Figure 1

Schematic illustration of design of transarterial chemoembolization (TACE) agents, in terms of polymeric beads or hydrogels, to occulate the blood supply of liver tumor and to synergically achieve localized chemotherapy to reduce its side effects on surrounding healthy tissues.

Figure 2

(A) Schematic illustration of tumor targeting HACE modified DOX/PLGA microsphere fabrication and treatment process as TACE reagent. (B) DOX/HACE MS (HACE modified DOX/PLGA microsphere) treatment could significantly decrease tumor size in McA-RH7777 tumor-implanted rat model, in comparison with control or DOX MS (DOX/PLGA microsphere) treatments. The tumor was recorded by magnetic resonance imaging. Scale bar is 1 cm. [Reproduced with permission from Lee et al. (2018), Copyright 2018 Taylor & Francis].

Figure 3

Schematic illustration of using amphiphilic hydrophobically modified chitosan (hmC) as cross-linking reagents for chitosan-glutaraldehyde (chitosan-GA) microbeads with surfaced modification of sulfated α-cyclodextrin (α-CD), as well as the self-assembly between hydrophobic chain of hmC and α-CD cavity, which could lead to formation of polymeric mesh outside microbeads for clotting applications. [Reproduced with permission from Arya et al. (2017), Copyright 2017 American Chemical Society].

Figure 4

(A) Schematic illustration of fabricating magnetic microbeads by using micro-fluid technique, to fabricate magnetic nanoparticle embedded PLGA microparticles. (B) Scanning electron microscopy observation of magnetic microparticles embedding (b-1) 50 wt% magnetic iron oxide nanoparticles and (b-2) 60 wt% magnetic iron oxide nanoparticles. [Reproduced with permission from Nosrati et al. (2018), Copyright 2018 American Chemical Society]. (C) Fabrication of magnetic PLGA-MMs (PLGA-magnetic microspheres) by emulsion of PLGA polymer and iron oxide magnetic nanoparticles, which was utilized as liver arterial embolization agent in VX2 liver tumor of rabbit. PLGA-MMs could block the local blood supply and induce local temperature increase upon exposure to alternating magnetic field, which could cause synergetic magnetic ablation of tumor. [Reproduced with permission from Liang et al. (2017), Copyright 2017 American Chemical Society].

Figure 5

(A) Synthesis of amphiphilic anionic PCLA-PUSSM copolymer with pH-dependent hydrogel formation ability. (B) Illustration for the microcatheter mediated intraarterial injection of PCLA-PUSSM hydrogel in rabbit HCC model. (C) CT observations revealed the shrinkage of tumor size when using PCLA-PUSSM hydrogel as TACE agent. [Reproduced with permission from Nguyen et al. (2016), Copyright 2016 Royal Society of Chemistry].

Figure 6

(A) Illustration of environment sensitive drug-eluting composite particles, as well as their low pH responsive chemotherapeutics release in hepatic vessels. [Reproduced with permission from Park et al. (2016), Copyright 2016 American Chemical Society]. (B) Synthesis of tumor targeting PLGA/pSMA microspheres with conjugation of MT1-MMP binding peptide and chemotherapeutic doxorubicin, for more precise transarterial chemoembolism therapy. [Reproduced with permission from Davaa et al. (2017), Copyright 2017 American Chemical Society].