Multifunctional Nano‐Biomaterials for Cancer Therapy via Inducing Enhanced Immunogenic Cell Death

Abstract

Immunotherapy is considered to be one of the most promising methods to overcome cancer. Immunogenic cell death (ICD), as a special form of cell death that can trigger an antitumor immune response, has attracted increasing attention for cancer immunotherapy. Presently, ICD‐mediating immunotherapy needs to overcome many hurdles including a lack of targeted delivery systems for ICD inducers, insufficient antitumor immunity, and the immunosuppressive tumor microenvironment. Recent research has demonstrated that nano‐biomaterials exhibit unique biochemphysical properties at the nanoscale, providing a prospective approach to overcoming these obstacles. In this review, the authors first survey the occurrence, processes, and detection methods of ICD. Subsequently, the recent advances of nano‐biomaterials applied to enhance ICD according to the key steps in the process of ICD, particularly with a focus on the mechanisms and lifting schemes are investigated. Finally, based on the achievement in the representative studies, the prospects and challenges of nanotechnology in ICD for cancer therapy are discussed to enable clinical translation.

Three Strategies in Engineering Nanomedicines for Tumor Microenvironment‐Enabled Phototherapy

“…There have been several recently published comprehensive reviews on breaking immunosuppressive barriers using therapeutic nanomaterials. [111] Considering the increasing accumulating evidence of the capacity of phototherapy to reprogram the immunosuppressive TME and activate the antitumor immune response, in this section, we briefly discuss the immunological aspects of PTT and PDT.…”

Immunogenic cell death (ICD) enhancers—Drugs that enhance the perception of ICD by dendritic cells

“…That said, there are efforts to combine distinct anticancer drugs, each of which alone do not induce ICD, among each other to obtain combinatorial ICD‐inducing effects 57 . Moreover, novel nanomedicine‐relevant procedures are allowing to generate novel galenic formulations for ICD induction that involve multiple compounds trascending the traditional limits of pharmacology 58–60 . Our approach to identify ICD inducers by drug screening is only apt for the identification of single compounds.…”

“…57 Moreover, novel nanomedicine-relevant procedures are allowing to generate novel galenic formulations for ICD induction that involve multiple compounds trascending the traditional limits of pharmacology. [58][59][60] Our approach to identify ICD inducers by drug screening is only apt for the identification of single compounds.…”

Amplifying “eat me signal” by immunogenic cell death for potentiating cancer immunotherapy

“…In general, DAMPs are released and cause dendritic cell (DC) maturation, for example, calreticulin (CALR) and high mobility box 1 (HMGB1) 8 . CALR exposes when tumor cells undergo ICD process and serves as a “eat me signal” for uptake via antigen‐presenting cells (APCs) and phagocytic cells, which provides a rich source of antigenic substances 9,10 . Extracellular HMGB1 binds to a variety of pattern recognition receptors, for example, end‐product‐specific receptor (AGER) and Toll‐like receptor 4 (TLR4) 11 .…”