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Injectable Supramolecular Polymer-Nanoparticle Hydrogels for Cell and Drug Delivery Applications
Published on: February 7, 2021
Supramolecular hydrogel for programmable delivery of therapeutics to cancer multidrug resistance
Liang-Hsin Chen1, Nai-Wen Liang1, Wei-Yuan Huang1
1Department of Materials Science and Engineering, National Tsing Hua University, Hsinchu City 30013, Taiwan.
Abstract:
Multidrug resistance (MDR) has been considered as a major adversary in oncologic chemotherapy. To simultaneously overcome drug resistance and inhibit tumor growth, it is essential to develop a drug delivery system that can carry and release multiple therapeutic agents with spatiotemporal control. In this study, we developed a hydrogel containing an enzyme-cleavable peptide motif, with a network structure formed by 4-armed polyethylene glycol (PEG) crosslinked by complementary nucleic acid sequences. Hydrogen bond formation between nucleobase pairing allows the hydrogel to be injectable, and the peptide motif grants deliberate control over hydrogel degradation and the responsive drug release. Moreover, MDR-targeted siRNAs are complexed with stearyl-octaarginine (STR-R8), while doxorubicin (Dox) is intercalated with DNA and nanoclay structures in this hydrogel to enhance therapeutic efficacy and overcome MDR. The results show a successful configuration of a hydrogel network with in situ gelation property, injectability, and degradability in the presence of tumor-associated enzyme, MMP-2. The synergistic effect by combining MDR-targeted siRNAs and Dox manifests with the enhanced anti-cancer effect on drug resistant breast cancer cells in both in vitro and in vivo tumor models. We suggest that with the tailor-designed hydrogel system, multidrug resistance in tumor cells can be significantly inhibited by the co-delivery of multiple therapeutics with spatial-temporal control release.
Insights
This study presents an injectable hydrogel for cancer therapy that co-delivers multiple drugs. This system effectively overcomes multidrug resistance (MDR) and inhibits tumor growth in preclinical models.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Oncology
Background:
- Multidrug resistance (MDR) significantly hinders effective cancer chemotherapy.
- Developing controlled drug delivery systems is crucial for overcoming MDR and improving therapeutic outcomes.
Purpose of the Study:
- To engineer an injectable hydrogel for spatiotemporal co-delivery of multiple anti-cancer agents.
- To address and overcome multidrug resistance (MDR) in cancer treatment.
Main Methods:
- Fabrication of a 4-armed polyethylene glycol (PEG) hydrogel crosslinked with nucleic acid sequences and incorporating an enzyme-cleavable peptide.
- Complexation of MDR-targeted siRNAs with stearyl-octaarginine (STR-R8) and intercalation of doxorubicin (Dox) with DNA and nanoclay within the hydrogel.
- Evaluation of hydrogel properties including in situ gelation, injectability, and MMP-2-triggered degradation, alongside in vitro and in vivo anti-cancer efficacy studies.
Main Results:
- Successful development of an injectable hydrogel with controlled degradation and drug release properties.
- Demonstration of enhanced therapeutic efficacy through the synergistic action of co-delivered MDR-targeted siRNAs and doxorubicin.
- Significant inhibition of tumor growth and overcoming of drug resistance in both in vitro and in vivo models of drug-resistant breast cancer.
Conclusions:
- The developed hydrogel system enables controlled co-delivery of therapeutics, effectively combating multidrug resistance.
- This innovative approach holds promise for enhancing cancer chemotherapy by overcoming MDR and improving treatment efficacy.
- Tailor-designed hydrogels offer a promising strategy for inhibiting tumor cell multidrug resistance through spatial-temporal controlled release of multiple agents.
