Polymer Hydrogels for Cancer Therapy

A special issue of Gels (ISSN 2310-2861). This special issue belongs to the section "Gel Applications".

Deadline for manuscript submissions: closed (10 January 2024) | Viewed by 15495

Special Issue Editors


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Guest Editor
1. Bone and Tumour Bioengineering Group, Faculty of Health, School of Biomedical Sciences, Max Planck Queensland Centre, Queensland University of Technology (QUT), Brisbane, QLD 4059, Australia
2. Translational Research Institute, (TRI), Brisbane, QLD 4102, Australia
Interests: cancer models; tissue engineering; tumor microenvironment; bioengineering; biomaterials; bone; bone metastasis; prostate cancer; breast cancer; personalized medicine; physical science of cancer; hydrogels; scaffolds; bioprinting

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Guest Editor
1. Gelomics Pty Ltd, Brisbane, QLD 5049, Australia
2. Herston Biofabrication Institute, Metro North Hospital and Health Services, Herston, QLD 4006, Australia
3. Centre for Biomedical Technologies, Queensland University of Technology (QUT), Brisbane, QLD 4059, Australia
4. School of Information Technology and Electrical Engineering, Faculty of Engineering, Architecture and Information Technology, The University of Queensland, St Lucia, QLD 4067, Australia
Interests: hydrogels; 3D cell culture; tissue engineering; regenerative medicine; 3D bioprinting
Light Activated Biomaterials Group, University of Otago, Christchurch 8011, New Zealand
Interests: hydrogels; 3D bioprinting; biofabrication; tissue engineering; regenerative medicine

Special Issue Information

Dear Colleagues,

The Special Issue on ‘Polymer Hydrogels for Cancer Therapy’ is dedicated to recent advancements in the synthesis, fabrication, characterization, and use of polymer-based hydrogels for cancer research. With a focus on cancer treatment, post-surgery tissue regeneration and disease modelling, a broad range of topics from fundamentals, physicochemical and biological characterization, and applied aspects will be discussed. This includes polymeric hydrogels as drug delivery systems, in vitro and in vivo cancer models, and personalized medicine platforms.

When treating heterogenous and lethal diseases such as cancers, it is now well-known that tumor resection surgery coupled with systemic chemotherapy often includes heavy side-effects and poor drug efficiency at the tumor site, while reducing healing time from surgery. Hydrogels, which are comprised of water insoluble three-dimensional networks of polymer chains with tunable chemistry and degradation profiles, have been proposed as an attractive alternative to this issue. They promise localized controlled drug release at the tumor site upon passive or stimuli-based response (pH, temperature), and can be coupled with tissue regenerative strategies to repair the diseased tissue. Yet, the full potential of such systems is yet to be demonstrated and translated to the clinic. The precise control of hydrogels as drug delivery systems necessitates a deeper mechanism-driven design and understanding, and characterization at multiple scales. This includes, among others, molecular and supramolecular architecture, release kinetics, and macroscale behavior upon degradation. Physicochemical characteristics equally require correlation with biological assessment in vitro and in vivo but also must be designed with a stronger real-world mindset. Some of the related issues indeed involve lack of; translational feasibility; easy-to-use biofabrication strategies; automation; and scale-up manufacture, which all need addressing to warrant clinic adoption in the future.

In cancer modelling and personalized medicine, synthetic and semi-synthetic hydrogels represent an excellent alternative to basement membrane extracts (BME) such as Matrigel. As highly tailorable biomaterials for tumor bioprinting, hydrogels open the door to more physiological (non-2D) mechanistic cancer study and drug screening. Hydrogels offer inertness or directed cell induction with added ECM components, and therefore provide the ability for cells to deposit their own ECM or provide cues to develop a specific phenotype with increased tumor microenvironment mimicry. These options mean that decreased biomaterial heterogeneity is achievable when using synthetic or semi-synthetic materials, while Matrigel compounds patient heterogeneity with its intrinsic batch-to-batch variability and inability to control key physical parameters such as the ECM stiffness. While PEG-based hydrogels have been a well-studied approach to address the Matrigel conundrum, many new polymers, copolymers and composite polymers have emerged to provide enhanced support to the culture of patient-derived cancer organoids and explants, and will be discussed in this issue.

Since it is impossible to cover all aspects of hydrogels for cancer science in one issue, this Special Issue will contain only the best representative, high-quality, examples that bridge multiple research gaps in the field, in the hope to stimulate new research in polymer hydrogels for cancer research.

Dr. Nathalie Bock
Dr. Christoph Meinert
Dr. Khoon Lim
Guest Editors

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Keywords

  • polymer chemistry
  • polymer synthesis
  • bioprinting
  • biofabrication
  • controlled drug delivery
  • cancer therapy
  • injectable hydrogels
  • cancer models
  • preclinical hydrogel models
  • high-throughput hydrogels
  • hydrogel composites
  • tumor microenvironment
  • extracellular matrix
  • tissue engineering
  • regenerative medicine

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Published Papers (5 papers)

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Research

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15 pages, 7618 KiB  
Article
Assessing Polysaccharides/Aloe Vera–Based Hydrogels for Tumor Spheroid Formation
by Petruța Preda, Ana-Maria Enciu, Cristiana Tanase, Maria Dudau, Lucian Albulescu, Monica-Elisabeta Maxim, Raluca Nicoleta Darie-Niță, Oana Brincoveanu and Marioara Avram
Gels 2023, 9(1), 51; https://doi.org/10.3390/gels9010051 - 7 Jan 2023
Cited by 4 | Viewed by 2845
Abstract
In vitro tumor spheroids have proven to be useful 3D tumor culture models for drug testing, and determining the molecular mechanism of tumor progression and cellular interactions. Therefore, there is a continuous search for their industrial scalability and routine preparation. Considering that hydrogels [...] Read more.
In vitro tumor spheroids have proven to be useful 3D tumor culture models for drug testing, and determining the molecular mechanism of tumor progression and cellular interactions. Therefore, there is a continuous search for their industrial scalability and routine preparation. Considering that hydrogels are promising systems that can favor the formation of tumor spheroids, our study aimed to investigate and develop less expensive and easy-to-use amorphous and crosslinked hydrogels, based on natural compounds such as sodium alginate (NaAlg), aloe vera (AV) gel powder, and chitosan (CS) for tumor spheroid formation. The ability of the developed hydrogels to be a potential spheroid-forming system was evaluated using MDA-MB-231 and U87MG cancer cells. Spheroid abilities were influenced by pH, viscosity, and crosslinking of the hydrogel. Addition of either AV or chitosan to sodium alginate increased the viscosity at pH 5, resulting in amorphous hydrogels with a strong gel texture, as shown by rheologic analysis. Only the chitosan-based gel allowed formation of spheroids at pH 5. Among the variants of AV-based amorphous hydrogels tested, only hydrogels at pH 12 and with low viscosity promoted the formation of spheroids. The crosslinked NaAlg/AV, NaAlg/AV/glucose, and NaAlg/CS hydrogel variants favored more efficient spheroid formation. Additional studies would be needed to use AV in other physical forms and other formulations of hydrogels, as the current study is an initiation, in evaluating the potential use of AV gel in tumor spheroid formation systems. Full article
(This article belongs to the Special Issue Polymer Hydrogels for Cancer Therapy)
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22 pages, 4348 KiB  
Article
Semi-Synthetic Click-Gelatin Hydrogels as Tunable Platforms for 3D Cancer Cell Culture
by Luke Hipwood, Julien Clegg, Angus Weekes, Jordan W. Davern, Tim R. Dargaville, Christoph Meinert and Nathalie Bock
Gels 2022, 8(12), 821; https://doi.org/10.3390/gels8120821 - 12 Dec 2022
Cited by 8 | Viewed by 3673
Abstract
Basement membrane extracts (BME) derived from Engelbreth–Holm–Swarm (EHS) mouse sarcomas such as Matrigel® remain the gold standard extracellular matrix (ECM) for three-dimensional (3D) cell culture in cancer research. Yet, BMEs suffer from substantial batch-to-batch variation, ill-defined composition, and lack the ability for [...] Read more.
Basement membrane extracts (BME) derived from Engelbreth–Holm–Swarm (EHS) mouse sarcomas such as Matrigel® remain the gold standard extracellular matrix (ECM) for three-dimensional (3D) cell culture in cancer research. Yet, BMEs suffer from substantial batch-to-batch variation, ill-defined composition, and lack the ability for physichochemical manipulation. Here, we developed a novel 3D cell culture system based on thiolated gelatin (Gel-SH), an inexpensive and highly controlled raw material capable of forming hydrogels with a high level of biophysical control and cell-instructive bioactivity. We demonstrate the successful thiolation of gelatin raw materials to enable rapid covalent crosslinking upon mixing with a synthetic poly(ethylene glycol) (PEG)-based crosslinker. The mechanical properties of the resulting gelatin-based hydrogels were readily tuned by varying precursor material concentrations, with Young’s moduli ranging from ~2.5 to 5.8 kPa. All hydrogels of varying stiffnesses supported the viability and proliferation of MDA-MB-231 and MCF-7 breast cancer cell lines for 14 and 21 days of cell culture, respectively. Additionally, the gelatin-based hydrogels supported the growth, viability, and osteogenic differentiation of patient-derived preosteoblasts over 28 days of culture. Collectively, our data demonstrate that gelatin-based biomaterials provide an inexpensive and tunable 3D cell culture platform that may overcome the limitations of traditional BMEs. Full article
(This article belongs to the Special Issue Polymer Hydrogels for Cancer Therapy)
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Review

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32 pages, 2089 KiB  
Review
Composite Hydrogels with Included Solid-State Nanoparticles Bearing Anticancer Chemotherapeutics
by Alexandar M. Zhivkov, Trifon T. Popov and Svetlana H. Hristova
Gels 2023, 9(5), 421; https://doi.org/10.3390/gels9050421 - 17 May 2023
Cited by 4 | Viewed by 1837
Abstract
Hydrogels have many useful physicochemical properties which, in combination with their biocompatibility, suggest their application as a drug delivery system for the local and prorogated release of drugs. However, their drug-absorption capacity is limited because of the gel net’s poor adsorption of hydrophilic [...] Read more.
Hydrogels have many useful physicochemical properties which, in combination with their biocompatibility, suggest their application as a drug delivery system for the local and prorogated release of drugs. However, their drug-absorption capacity is limited because of the gel net’s poor adsorption of hydrophilic molecules and in particular, hydrophobic molecules. The absorption capacity of hydrogels can be increased with the incorporation of nanoparticles due to their huge surface area. In this review, composite hydrogels (physical, covalent and injectable) with included hydrophobic and hydrophilic nanoparticles are considered as suitable for use as carriers of anticancer chemotherapeutics. The main focus is given to the surface properties of the nanoparticles (hydrophilicity/hydrophobicity and surface electric charge) formed from metal and dielectric substances: metals (gold, silver), metal-oxides (iron, aluminum, titanium, zirconium), silicates (quartz) and carbon (graphene). The physicochemical properties of the nanoparticles are emphasized in order to assist researchers in choosing appropriate nanoparticles for the adsorption of drugs with hydrophilic and hydrophobic organic molecules. Full article
(This article belongs to the Special Issue Polymer Hydrogels for Cancer Therapy)
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35 pages, 5539 KiB  
Review
Recent Advances in Hydrogel-Based Phototherapy for Tumor Treatment
by Shuaiqi Gan, Yongzhi Wu, Xu Zhang, Zheng Zheng, Min Zhang, Li Long, Jinfeng Liao and Wenchuan Chen
Gels 2023, 9(4), 286; https://doi.org/10.3390/gels9040286 - 1 Apr 2023
Cited by 18 | Viewed by 3479
Abstract
Phototherapeutic agent-based phototherapies activated by light have proven to be safe modalities for the treatment of various malignant tumor indications. The two main modalities of phototherapies include photothermal therapy, which causes localized thermal damage to target lesions, and photodynamic therapy, which causes localized [...] Read more.
Phototherapeutic agent-based phototherapies activated by light have proven to be safe modalities for the treatment of various malignant tumor indications. The two main modalities of phototherapies include photothermal therapy, which causes localized thermal damage to target lesions, and photodynamic therapy, which causes localized chemical damage by generated reactive oxygen species (ROS). Conventional phototherapies suffer a major shortcoming in their clinical application due to their phototoxicity, which primarily arises from the uncontrolled distribution of phototherapeutic agents in vivo. For successful antitumor phototherapy, it is essential to ensure the generation of heat or ROS specifically occurs at the tumor site. To minimize the reverse side effects of phototherapy while improving its therapeutic performance, extensive research has focused on developing hydrogel-based phototherapy for tumor treatment. The utilization of hydrogels as drug carriers allows for the sustained delivery of phototherapeutic agents to tumor sites, thereby limiting their adverse effects. Herein, we summarize the recent advancements in the design of hydrogels for antitumor phototherapy, offer a comprehensive overview of the latest advances in hydrogel-based phototherapy and its combination with other therapeutic modalities for tumor treatment, and discuss the current clinical status of hydrogel-based antitumor phototherapy. Full article
(This article belongs to the Special Issue Polymer Hydrogels for Cancer Therapy)
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Other

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13 pages, 1502 KiB  
Systematic Review
Hydrogel on a Smart Nanomaterial Interface to Carry Therapeutics for Digitalized Glioma Treatment
by Xinyi Zhao, Bilal Javed, Furong Tian and Kangze Liu
Gels 2022, 8(10), 664; https://doi.org/10.3390/gels8100664 - 17 Oct 2022
Cited by 4 | Viewed by 2346
Abstract
Glioma is considered the primary brain tumor to cause brain illnesses, and it is difficult to treat and shows resistance to various routine therapeutics. The most common treatments to cure glioma are the surgical removal of tumors followed by adjuvant chemotherapy and radiation [...] Read more.
Glioma is considered the primary brain tumor to cause brain illnesses, and it is difficult to treat and shows resistance to various routine therapeutics. The most common treatments to cure glioma are the surgical removal of tumors followed by adjuvant chemotherapy and radiation therapy. The latest biocompatible interfaces have been incorporated into therapeutic modalities such as the targeted delivery of drugs using hydrogels to treat and manage brain glioma. This review illustrates the applications of the multimodal hydrogel as the carrier of therapeutics, gene therapy, therapeutic tactics, and glioma devices. The scientific articles were retrieved from 2019 to 2022 on Google Scholar and the Scopus database and screened to determine whether they were suitable for review. The 20 articles that fit the study are summarized in this review. These studies indicated that the sizes of the hydrogel range from 28 nm to 500 nm. There are 16 out of 20 articles that also explain the post-surgical application of hydrogels, and 13 out of 20 articles are employed in 3D culture and other structural manifestations of hydrogels. The pros of the hydrogel include the quick formulation for a sufficient filling of irregular damage sites, solubilizing hydrophobic drugs, continuously slowing drug release, provision of a 3D cell growth environment, improving efficacy, targetability of soluble biomolecules, increasing patient compliance, and decreased side effects. The cons of the hydrogel include difficult real-time monitoring, genetic manipulations, the cumbersome synchronized release of components, and lack of safety data. The prospects of the hydrogel may include the development of electronic hydrogel sensors that can be used to enhance guidance for the precise targeting patterns using patient-specific pathological idiosyncrasies. This technology has the potential to revolutionize the precision medicine approaches that would aid in the early detection and management of solid brain tumors. Full article
(This article belongs to the Special Issue Polymer Hydrogels for Cancer Therapy)
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