Table 2 Summary of strategies for targeting and remodeling the biophysiochemical TME
Biophysiochemical TME | Remodeling strategy | Nano-carrier | Guest drug | Application | Tumor types | Refs. | |
|---|---|---|---|---|---|---|---|
Physicochemical TME | Destroying REDOX Homeostasis | Catalyzing H2O2 in situ to produce O2 | Co9S8@MnO2-ICG/DOX | ICG/DOX | Self-generated oxygen enhanced PDT; promoted chemotherapy | Ovarian adenocarcinoma | [152] |
BiPt-PFA | Pt/Bi dots | Alleviated hypoxia; GSH depleted; sensitization radiation | Breast cancer | [153] | |||
Oxidase delivered to decompose metabolites and produce O2 | TA/Fe@GOD@DMONs | TA/Fe/GOD | Decomposing GOD to glucose and producing H2O2; effective CDT | Breast cancer | [154] | ||
Expanding ROS generation in the TME | GOD-Fe3O4@DMSN | GOD/ultrasmall Fe3O4 NPs | Glucose exhausted and Fenton reaction produced ROS to boost cancer cell apoptosis | Breast cancer | [159] | ||
IONP-GOD@ART | GOD/ART/Fe | Numerous ROS produced by "Metal oxidases" cascade and induce ICD | Breast cancer | [160] | |||
MSNs-PFH@PDA-ICG-PEG-FA | PFH/ICG | Self-generated ROS enhanced PDT | Breast cancer | [161] | |||
Consuming the existing GSH | PEG/Ce-Bi@DMSN | Ultrasmall ceria nanozymes | Elevated oxidative stress and relieved hypoxia in the TME | Cervical cancer | [163] | ||
IR-820/PFO@FA-MPPD | IR-820/PFO | Hypoxia relieved; GSH depletion; enhanced PDT effect | Hepatocellular carcinoma | [165] | |||
GDMON-P + OVA + CpG | Ovalbumin/a TLR9 agonist | A self-adjuvant for cancer vaccine; deplete GSH; increased ROS | Melanoma | [166] | |||
Mn-Fe- Co DMOS NPs | ICG | GSH depletion and improved O2-depended PDT | Breast cancer | [167] | |||
HMOS@MOF | CDDP/Zn2+/Cu2+ | GSH depletion; enhanced CDT and chemotherapy | NSCLC | [168] | |||
Suppressing the generation of GSH | MCN-AR@PCM | AIBI/Raloxifene | GSH synthesis suppression and O2-irrelevant radicals produced by AIBI to kill cancer cells | Breast cancer/glioblastoma | [169] | ||
DMSN-Au-Fe3O4 | Au/Fe3O4 | Au-mediated H2O2 self-supply and GSH biosynthesis inhibition | Breast cancer | [170] | |||
Reverse low pH of TME | Inhibiting the outflow of intracellular acid metabolites | DOX@MSNs-CAIX | DOX/A‑CAIX Ab | CAIs delivered to reduce TME Carbonic acid levels; Promoted toxicity of DOX | Breast cancer | [174] | |
HMONs@HCPT-BSA-PEI-CDM-PEG@ siMCT-4 | HCPT/siMCT-4 | Lactate efflux inhibition by role of siMCT4; enhanced chemotherapy | Melanoma/breast cancer | [175] | |||
Consumption of extracellular acidic metabolites | ODMSN-AQ4N-LOX | LOX/AQ4N | Lactate depletion metastasis and angiogenesis resistance; increased tumor hypoxia | Breast cancer | [114] | ||
Promoting intracellular acidic metabolites production and inhibit their effluvia | Me&Flu@MSN@MnO2-FA | Me/Flu | Increased intracellular lactate and decreased extracellular lactate; cancer cells acidosis | Breast cancer | [179] | ||
Biological TME | Remodeling energy metabolism | Consuming energy metabolites | HMBRN-GOx/TPZ | Gox/TPZ | Glucose consumption to starve cancer cells and increased TPZ toxicity | Astroblastoma/Breast cancer | [181] |
Inhibiting Warburg effect | CP-MSNP@DOX/siRNA | DOX/PKM2 siRNA | PKM2 gene silence to inhibit Warburg effect; enhanced chemotherapy | Breast cancer | [184] | ||
Remodeling ECM | Reduce ECM | MSN-Col-nc | Collagenase | Extracellular matrix degradation | Osteosarcoma | [185] | |
DN@MSN | DOX/a NO donor (S-nitrosothiol) | MMPs activated by NO to degrade collagen in the ECM | Breast cancer | [186] | |||
Remodeling extracellular vesicles | Decrease circulating sEVs levels | MSN-Exo | A-Exo | Decreased circulating A-Exo levels; attenuate A-Exo-induced lung metastasis | Lung cancer | [191] | |