Cancer Immunotherapy Using Bioengineered Micro/Nano Structured Hydrogels

Abstract

Hydrogels, a class of materials with a 3D network structure, are widely used in various applications of therapeutic delivery, particularly cancer therapy. Micro and nanogels as miniaturized structures of the bioengineered hydrogels may provide extensive benefits over the common hydrogels in encapsulation and controlled release of small molecular drugs, macromolecular therapeutics, and even cells. Cancer immunotherapy is rapidly developing, and micro/nanostructured hydrogels have gained wide attention regarding their engineered payload release properties that enhance systemic anticancer immunity. Additionally, they are a great candidate due to their local administration properties with a focus on local immune cell manipulation in favor of active and passive immunotherapies. Although applied locally, such micro/nanostructured can also activate systemic antitumor immune responses by releasing nanovaccines safely and effectively inhibiting tumor metastasis and recurrence. However, such hydrogels are mostly used as locally administered carriers to stimulate the immune cells by releasing tumor lysate, drugs, or nanovaccines. In this review, the latest developments in cancer immunotherapy are summarized using micro/nanostructured hydrogels with a particular emphasis on their function depending on the administration route. Moreover, the potential for clinical translation of these hydrogel-based cancer immunotherapies is also discussed.

Keywords: caner immunotherapy; implantable hydrogels; injectable hydrogels; nanogels; nanovaccine; sprayable hydrogels.

Figure 1

a) Immunotherapy and Chemotherapy challenges in solid tumors: The main challenges are the bold font, direct causes are pink, and passive feedback is green. b) General classification of cancer immunotherapy approaches in solid tumors.

Figure 2

Hydrogels' physiochemical traits intricately shape their role in immunotherapy. Factors like degradation kinetics, mesh size, and biomolecule‐polymer affinity matter. Nanogels' unique properties enable efficient immune modulation. Hydrogels also support therapeutic cell growth, aided by nanogel nutrient conveyance. Their adjustability in mechanics and chemistry allows localized cell reprogramming, driven by tailored cues.

Figure 3

Schematic presentation of hydrogels in cancer immunotherapy.

Figure 4

ICI administration routes.

Figure 5

Schematic showing the process of CAR‐T cell administration in solid tumors using modified polymeric hydrogels.

Figure 6

Cancer vaccine features. Ag: Antigen, TAA: Tumor Associated Antigen, DC: Dendritic Cell, LPS: Lipopolysaccharide, P:IC: Poly:inosinic‐poly:cytidylic acid, LNP: Lipid based nanoparticle, EXV: extra cell membrane vesicles.

Figure 7

Nanogels in cancer immunotherapy.