Improving nanochemoimmunotherapy efficacy by boosting “eat-me” signaling and downregulating “don't-eat-me” signaling with Ganoderma lucidum polysaccharide-based drug delivery

Abstract

Prophagocytic mixed nanodrugs are developed to enhance macrophage phagocytosis by encapsulating ICD inducer doxorubicin and CD47 inhibitor gefitinib with immunostimulatory polysaccharides from Ganoderma lucidum.

Advanced Strategies for Strengthening the Immune Activation Effect of Traditional Antitumor Therapies

“…To conduct this strategy, Pang et al loaded the tumor ICD inducer DOX and CD47 inhibitor gefitinib in the Ganoderma lucidum polysaccharide (GLP) to fabricate a MIXNP nanoplatform (Figure 5C). 72 First, the DOX-mediated chemotherapy would cause the ICD of tumor cells to release tumor antigens, while gefitinib would transmit the "eat me" signal to macrophages (one kind of APCs) to promote the antigen uptake through the inhibition of CD47 molecules. Besides, the GLP component could not only mitigate the side effects of chemotherapy but also stimulate the expression of activation markers (CD80, MHC I) and hasten the antigen cross-presentation process of DCs.…”

“…(C) Schematic illustration of the MIXNP-mediated strong immune activation for tumor by initiating the “eat me” signal of APCs during chemotherapy. Reproduced with permission from ref . Copyright 2023 The Royal Society of Chemistry.…”

“…As well-known, most tumor cells overexpressed CD47 to ligate with the SIRPa on the phagocytes (DCs and macrophages) to transmit a “don’t eat me” signal, which will then greatly inhibit the uptake of tumor antigen by APCs. − Accordingly, blocking the CD47 pathway during TTS also shows good potential in enhancing their immune activation effect. To conduct this strategy, Pang et al loaded the tumor ICD inducer DOX and CD47 inhibitor gefitinib in the Ganoderma lucidum polysaccharide (GLP) to fabricate a MIXNP nanoplatform (Figure C) . First, the DOX-mediated chemotherapy would cause the ICD of tumor cells to release tumor antigens, while gefitinib would transmit the “eat me” signal to macrophages (one kind of APCs) to promote the antigen uptake through the inhibition of CD47 molecules.…”