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Review
. 2023 Oct 4;15(10):2421.
doi: 10.3390/pharmaceutics15102421.

Hydrogel-Based Therapeutics for Pancreatic Ductal Adenocarcinoma Treatment

Jinlu Liu  1 , Wenbi Wu  2 , Qing Zhu  1 , Hong Zhu  1
Affiliations
Review

Hydrogel-Based Therapeutics for Pancreatic Ductal Adenocarcinoma Treatment

Jinlu Liu et al. Pharmaceutics. .

Abstract

Pancreatic ductal adenocarcinoma (PDAC), one of the deadliest malignancies worldwide, is characteristic of the tumor microenvironments (TME) comprising numerous fibroblasts and immunosuppressive cells. Conventional therapies for PDAC are often restricted by limited drug delivery efficiency, immunosuppressive TME, and adverse effects. Thus, effective and safe therapeutics are urgently required for PDAC treatment. In recent years, hydrogels, with their excellent biocompatibility, high drug load capacity, and sustainable release profiles, have been developed as effective drug-delivery systems, offering potential therapeutic options for PDAC. This review summarizes the distinctive features of the immunosuppressive TME of PDAC and discusses the application of hydrogel-based therapies in PDAC, with a focus on how these hydrogels remodel the TME and deliver different types of cargoes in a controlled manner. Furthermore, we also discuss potential drug candidates and the challenges and prospects for hydrogel-based therapeutics for PDAC. By providing a comprehensive overview of hydrogel-based therapeutics for PDAC treatment, this review seeks to serve as a reference for researchers and clinicians involved in developing therapeutic strategies targeting the PDAC microenvironment.

Keywords: drug-delivery system; hydrogel; immunosuppressive tumor microenvironment; pancreatic ductal adenocarcinoma.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The mechanism of hydrogel-based therapeutics for PDAC treatment.
Figure 2
Figure 2
The formation of the immunosuppressive TME of PDAC.
Figure 3
Figure 3
The chemical structure of typical synthetic (a) and natural (b) polymers for hydrogel-based delivery systems in PDAC.
Figure 4
Figure 4
A schematic illustration is presented to demonstrate the application of PFC-alginate hydrogel delivering GEM and ICG on a xenograft model derived from patient-derived organoids of PDAC. The hydrogel composite was utilized to deliver and release chemotherapeutics and sonosensitizers at the tumor site via in situ injection. Upon exposure to low-intensity ultrasound, the liquid-phase PFC underwent a phase transition into a gas, leading to the release of dissolved O2, thereby enhancing the efficacy of sonodynamic therapy. Copyright from ELSEVIER 2023.
Figure 5
Figure 5
The structure of pentablock terpolypeptide and the illustration of the hydrogel with encapsulated drug implanted in least invasive way. The hydrogel could melt only in vicinity of cancerous tissue due to the lower pH, leading to targeted and directional drug delivery. Copyright from ACS Publications 2023.
Figure 6
Figure 6
The schematic illustration depicts the process of formulating the chitosan-based hydrogel (a) and highlights the underlying mechanism of reshaping the tumor microenvironment for the treatment of pancreatic cancer after surgery (b).
See this image and copyright information in PMC

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