Thermosensitive hydrogel releasing nitric oxide donor and anti-CTLA-4 micelles for anti-tumor immunotherapy

Abstract

Due to their autosynchronous roles in shaping the anti-tumor immune response, complex immune regulatory networks acting both locally within the tumor microenvironment as well as in its draining lymph nodes play critical roles in the cancer immunotherapy response. We describe herein a thermosensitive co-polymer hydrogel system formed from biocompatible polymers gelatin and Pluronic® F127 that are widely used in humans to enable the sustained release of a nitric oxide donor and antibody blocking immune checkpoint cytotoxic T-lymphocyte-associated protein-4 for efficient and durable anti-tumor immunotherapy. By virtue of its unique gel formation and degradation properties that sustain drug retention at the tumor tissue site for triggered release by the tumor microenvironment and formation of in situ micelles optimum in size for lymphatic uptake, this rationally designed thermosensitive hydrogel facilitates modulation of two orthogonal immune signaling networks relevant to the regulation of the anti-tumor immune response to improve local and abscopal effects of cancer immunotherapy.

Design, preparation and pharmacodynamics of ICG-Fe(Ⅲ) based HCPT nanocrystals against cancer

“…The ICG exposed with laser group showed unevenly tumor sizes which possibly caused by the individual differences of mice. Mice are biologically independent samples, they have inconsistent logarithmic tumor growth cycles [55 , 56] . For this reason, we set 6 mice per group to avoid the possible individual differences.…”

Nanomaterials: A powerful tool for tumor immunotherapy

“…Still, its function is inhibited by the expansion of other immune cells expressing CTLA-4. Thomas et al (130) synthesized a thermosensitive hydrogel F127-g-using Pluronic ® F127 and gelatin by a simple chemical coupling Gelatin hydrogel loaded with NO donor GSNO and CTLA-4 antibody. The results showed that the F127-g-gelatin hydrogel combined with GSNO and CTLA-4 antibody had more substantial anti-tumor effects on tumor-bearing mice than saline, bare hydrogel and free GSNO + CTLA-4 antibody.…”

Inclusion Complexation of S-Nitrosoglutathione for Sustained NO Release and Reduced Device Infection

“…The cumulative NO release is calculated to be 2.48×10 -4 and 2.36×10 -4 moles, respectively, confirming that the presence of αCD does not consume NO. NO-releasing hydrogels have been shown to promote wound healing in topical applications [55], enhance tumor immunotherapy as injectables [56], and protect medical implants as coatings [8].…”