Table 5.

pH-sensitive nanoparticles in cancer immunotherapy

Nanoparticle	Cancer type/cell line	Size (nm)/zeta potential (mV)	Highlights	Reference
PEG/PEI/CAD nanoparticles	Breast cancer/4T1 cells	At a range of 100–250 nm/at a range of 10–20 mV	Delivery of doxorubicin and its release in a pH-sensitive manner Immunogenic cell death induction The acidity of the endosome induces cleavage of cis-aconityl Recruitment of dendritic cells	[512]
Hollow silica nanostructures	Breast cancer/4T1 cells	100 nm/+11 mV	Increased retention in response to low pH level of TME Targeting mitochondria and increasing ROS levels Stimulation of photodynamic therapy Combination with checkpoint inhibitors mediates anti-tumor immunity	[513]
Dextran-modified BLZ-945 nanocarriers	Breast cancer/4T1 cells	11.35, 112.4, and ∼135.6 nm	Presence of a borate ester bond as a pH-sensitive bond Immunogenic cell death induction Dendritic cell maturation, TAM depletion and T cell infiltration	[514]
Manganese nanoparticles	Melanoma/B16-OVA cells	130 nm	Mn2 + and 2-methylimidazole (2-MI) have been used to encapsulate ovalbumin with pH-sensitive features and the ability of dendritic cell maturation in cancer immunotherapy	[515]
Mesoporous silica nanostructures	-	146 nm	pH-sensitive feature and delivery of R848 Uptake of nanoparticles by antigen-presenting cells Stimulation of dendritic cells and boosting T cell-mediated immune responses	[516]
Peptide-functionalized nanobubbles	Breast cancer/4T1 cells	173.8 nm/-1.53 mV	Functionalization of nanobubbles with anti-PD-L1 peptide Loading Ce6, metformin and perfluorohexane in nanobubbles Accumulation of nanoparticles in acidic pH causes detachment of PEG ligands and then, exposure of peptide to suppress PD-L1 Hypoxia relief by metformin and increasing potential of Ce6 in cancer therapy Increasing anti-tumor immunity and prevention of immunosuppression	[517]
Polymer-lipid complexes	Lymphoma/E.G7-OVA cells	-	The polymer-lipid-embedded liposomes release ovalbumin in response to pH and stimulate anti-cancer immunity by releasing ovalbumin in the cytoplasm of dendritic cells	[518]
Polymer-modified liposomes	Lymphoma/E.G7-OVA cells	100 nm/−15.7 mV and 1.3 mV at pH 7.4 and pH 5.5	pH-responsive feature and cationic lipid inclusion Delivery of ovalbumin Increasing cytokine generation Antigen presentation through MHC-I and MHC-II	[519]
Liposome	Lymphoma/E.G7-OVA cells	136, 108 and 115 nm/-0.87, -11 and − 6.1 mV	Modification of liposomes with polymer Destabilization of liposomes in pH 6 Uptake of liposomes by dendritic cells Delivery of ovalbumin to cytosol Tumor growth suppression	[520]
Polymer-modified liposomes	Lymphoma/E.G7-OVA cells	97, 100, 88, 110, 108 and 109 nm/-18, -19, -11, -63, -65 and − 60 mV	Inclusion of cationic lipid and CpG-DNA Inducing dendritic cells to secrete cytokines Stimulation of antigen-specific immune responses pH-sensitive feature	[521]
Biomimetic nanoparticles	Breast cancer/4T1 cells	102.86 nm	Coating manganese nanoparticles with hybrid membranes Membrane is developed from mesenchymal stem cell membrane and pH-sensitive liposomes Targeted delivery of BPTES Inducing STNG pathway and M1 polarization of macrophages Relief of immunosuppression TME	[522]
Polysaccharide-based polymers	Lymphoma/E.G7-OVA cells	157 nm/-50 mV	Stimulation of dendritic cells Cytoplasmic delivery of antigen Th1 cytokine production by dendritic cells	[523]
Liposomes	Melanoma/B16-OVA cells	401, 754, 636 and 674 nm	pH-sensitive liposomes deliver STING and TLR9 agonist Increasing Th1 immune responses in tumor suppression	[524]