Customer Case Study: How AniView Imaging System Help Scientist Developing Molecular Hydrogels for D-L1 Blockade Therapy

Zhao Xing’s team from the West China Hospital of Stomatology at Sichuan University,has made research progress in developing molecular hydrogels for D-L1 blockade therapy.

The Aniview in vivo imaging system was used in the study on the retention effect of hydrogel on apdl1 in mice and the therapeutic effect on melanoma in mice.

Results from this research have been published in Advanced Functional Materials (IF=19.924, Q1).

It is commonly believed that the immune system is initially involved in the initiation, promotion and progression of tumors. CD8+ cytotoxic lymphocytes (CD8+T) present tumor cells by directly recognizing and decomposing drug antigens that trigger anti-tumor activity and participate in orchestrating a plethora of systemic immune responses.

However, tumors upregulate the expression of programmed cell death protein ligand-1 (PD-L1), which binds specifically to its receptor, PD-1, which is expressed on CD8+T cells; Therefore, it escapes the anti-tumor immune response mediated by CD8+T cells.

It has been confirmed that inosine can promote the proliferation and function of CD8+ T cytotoxic lymphocytes (CD8+ T) under glucose-restricted conditions and enhance the efficacy of programmed cell death protein ligand-1 (PD-L1) blockade therapy. However, systemic administration of inosine and anti-PD-L1 antibody (aPDL1) with high frequency and a large dose is required, which inevitably reduces bio-availability and leads to serious immunological side effects.

Therefore, it is essential to develop a drug delivery system to achieve the gradient release of inosine and apdl1 for local immunotherapy.

In this study, the authors successfully developed inosine-phenylenediboronic-isoguanosine (IPBisoG).

Both in vitro and in vivo studies have shown that IPBisoG hydrogels with biocompatibility and biodegradability have excellent stability and self-healing properties. In addition, IPBisoG hydrogel could realize the gradual and sequential release of inosine and aPDL1. Inosine, which enhances the proliferation and function of CD8+T cells, together with aPDL1, a blocker of immunosuppressive pathways in the tumor microenvironment, can highly enhance the in vivo efficacy of PD-L1 blockade therapy. The use of IPBisoG hydrogels have also been shown to trigger systemic immune responses.

▲ Schematic illustration of the formation of IPBisoG hydrogel and its exploration in PD-L1 blockade therapy as an injectable and controlled released supramolecular hydrogel via peritumoral injection administration procedures.

The authors labeled aPDL1 with Cy5 and encapsulated it with IPBisoG hydrogel, and then injected it into mice through the tail vein to evaluate the retention of aPDL1 in animals by IPBisoG hydrogel.

Using the AniView animal in vivo imaging system, it was observed that aPDL1 encapsulated by IPBisoG hydrogel still had an obvious signal 72 hours after injection, indicating that IPBisoG hydrogel can prolong the retention time of aPDL1 in the tumor of mice.

The same conclusion was obtained by analyzing the intensity of the fluorescence signal at 60 hours.

▲ IPBisoG hydrogel for aPDL1 retention in mice

The authors also constructed a bioluminescent melanoma mouse model, and then observed it with the Aniview animal in vivo imaging system. The results showed that IPBisoG hydrogel +aPDL1 could significantly inhibit the growth of melanoma, and the in vitro anatomical experiments could also support this conclusion.

▲ therapeutic effect of ipbisog hydrogel on melanoma in mice

Our Aniview series multimodal animal in vivo imaging system was used in the study of the retention effect of IPBisoG hydrogel on aPDL1 in mice and the therapeutic effect on melanoma in mice.

In this study, researchers designed and synthesized a new supramolecular hydrogel derived from natural products (inosine and isoG). IPBisoG hydrogel can significantly enhance tumor drug retention, byacting as a reservoir for inosine and aPDL1 release. In addition, local delivery of IPBisoG hydrogel can effectively trigger the systemic antitumor immune response. This novel supramolecular hydrogel provides a promising strategy for cancer immunotherapy and an innovative approach for the design of other novel drug delivery systems in the future.

BLT Biotechnology in vivo imaging system

AniView multi-model in vivo animal imaging system featuring ultra-high sensitivity (scientific-grade CCD cameras), lower fluorescence background, user-friendly software operation, intelligent scheme design, and more optional modules, making it an excellent partner for scientific research.

Reference:

https://doi.org/10.1002/adfm.202204273