. Author manuscript; available in PMC: 2022 Sep 1.

Published in final edited form as: Adv Drug Deliv Rev. 2021 Jul 21;176:113884. doi: 10.1016/j.addr.2021.113884

Table 1.

Summary of notable examples and their mechanism of action.

Biological Function	Mechanism of Action	Notable Examples & References
ROS Scavenging	Cleavage of diselenide bonds in presence of oxidants	- SeNPs for cancer therapy [19] - SeNPs for RNase delivery [22]
ROS Scavenging	Catalyzing decomposition of H₂O₂	- MnO₂ NPs for anti-cancer therapy [24, 25, 27]

ROS Generating	Material acts as oxidant to induce ROS stress in low pH environment (i.e., TME), leading to apoptosis	- SeNP with 5-fluorouracil [28] - SeNPs for anti-cancer drug delivery [31, 32] - CeO₂ NPs for anti-cancer drug delivery [34, 35]
ROS Generating	Impair mitochondrial response and/or interrupt redox cycling	- AgNP for anti-cancer [37] or anti-bacterial [41] drug delivery - AuNP for cancer therapy [42, 43] - Pluronic micelles for anti-cancer drug delivery [45, 46]

Immuno-activating	Activation of cGAS-STING pathway, causing release of type I IFN and DC activation/ maturation, or cytotoxic T cell response	- CS NPs for vaccine delivery [66, 67] - PC7A NPs for antigen delivery [99, 100] - Synthetic LNP for mRNA delivery [101]
	Cytokine secretion and T cell proliferation	- LMW-HA-based microneedles for cancer vaccines [74, 75]
	Activation of MyD88-dependent type I IFN secretion and NF-κB signaling pathways	- Pullulan nanogel for anticancer antigen delivery [81]
	B cell activation	- Alum NPs for immunogen delivery [86, 87]
	Activation of macrophages with wound-healing phenotype	- PAMAM-G4 dendrimers for neural immune cell activation [98]

Anti-inflammatory	Binding of cell-free DNA (cfDNA)	- PAMAM-G3 for cancer [104] and autoimmune disease treatment [12]
	Chemoattraction of neutrophils	- CS scaffold for regenerative treatment [108, 110]
	Inhibition of NF-κB and TNF-α pathways	- HMW-HA drug delivery systems for cancer treatment [116, 117]
	Reduced cell adhesion	- Heparin nanosystems for wound healing [125, 126]

Immuno-evasive	Modulation of lymphocyte and macrophage recruitment reduces myofibroblast recruitment and collagen deposition	- Alginate microcapsules for anti-fibrotic applications [134, 137] - CS gel for glaucoma [140]
Immuno-evasive	Formation of protective hydration shells through electrostatic interactions lowers cell adhesion and reduced immune cell recruitment	- Poly-MPC coated alginate microcapsules for anti-fibrotic applications [129] - Sulfobetaine (SB)/carboxybetaine (CB)- coated microspheres for cell encapsulation [141]