Table 2 Chitosan-based nanomaterials for systemic administration
Type of nanomaterials | Properties of chitosan | Payload | Type of NPs targeting | Assembly mechanism or preparation method | Characterization | Targeting mechanism or drug release mechanism | Animal model | Refs. |
|---|---|---|---|---|---|---|---|---|
siRNA-loaded chitosan-lactate NPs | DD: 87.7% | Anti-CTLA-4 | Passive targeting | Polyelectrolyte complexation | size: 77 nm; PDI: ~ 0.2; surface charge:  + 14 mV; | Tumor targeting via EPR effects | CT26, and 4 T1 cell xenograft mice model | [254] |
PTX-loaded chitosan–polyethylene glycol nanofiber | Mw: 3.9 kDa | PTX | Passive targeting | Chemical covalent linkage | 1) Nanofiber: size: 565 nm; surface charge: + 0.8 mV; 2) smaller NPs: size: 20.6 nm; surface charge: -5.8 mV | (1) Nanofiber break down into smaller NPs by interaction with serum proteins; (2) Tumor targeting via EPR effects | Aggressive and drug-resistant breast cancer and melanom mouse models | [63] |
miRNA mimics/TPP/PEG-chitosan NPs | Mw:50 ~ 190 kDa DD: 75 ~ 85% | miRNA (miR-33) | Active targeting | Polyelectrolyte complexation | Size: 150 ~ 200 nm; Surface Charge: + 2 ~  + 6 mV | (1) Naïve macrophages-targeting; (2) ABCA1 gene silencing for regulating the cholesterol efflux | acLDL-loaded/[3H]cholesterol-labeled peritoneal macrophages injected mice model | [68] |
siRNA/α-cyclam-p-toluic acid (CPTA)-modified chitosan NPs | DD: 85% Mw: 56 kDa CPTA: chitosan = 1:10 | p53-siRNA | Active targeting | Polyelectrolyte complexation | Size: 129.5 nm; PDI: 0.23; Surface charge: + 14.8 mV | (1) CPTA-CS targeted renal CXCR4 receptor (2) Chitosan targeting proximal tubule cellular surfaces | Ischemia–reperfusion injury (I/R) induced acute kidney injury (AKI) mice model | [71] |
Mesoporous silica shell/POM nanoclusters coated with chitosan-FA | Mw: 60 kDa | DOX | Active targeting | electrostatic interaction | size: ~ 120 nm; surface charge: − 10.5 mV | FA targeting FA receptor in tumor cells | U14 cell xenograft mice model | [61] |
SS-31/HA/chitosan NPs | – | SS-31 | Active targeting pH-responsive | Polyelectrolyte complexation | Size: 53 nm; PDI: 0.2; Surface charge: − 19.6 mV; EE: 94.0%, LC: 10.5% | (1) CD44-targeting (HA), mitochondria-targeting (SS31) (2) pH-responsive releasing | I/R-induced AKI mice model | [88] |
siRNA/ HA dialdehyde/chitosan | Low Mw: 29 kDa DD: 93.7% | Bcl-2 siRNA | Active targeting | Polyelectrolyte complexation | size: 100 ~ 120 nm; PDI: ~ 0.1 | CD44-targeting (HA) | T24 tumor cell xenograft mice model | [255] |
SiRNA/PEG/ mannose modifed-TMC/ PC NPs | TMC Mw: 200 kDa DD: 85% | VEGF siRNA/PIGF siRNA | Active targeting pH-responsive | Polyelectrolyte complexation | Size: 144 nm; PDI: 0.14; surface Charge: + 15.7 mV | Acidic-responsive benzimide bond cleavage of PC mannose-mediated active-targeting | In situ and lung metastatic breast cancer models | [256] |
Red blood cell (RBC)-hitchhiking drug/TPP/chitosan NPs | DD:85% | Methylprednisolone sodium succinate | Active targeting | Ionotropic-gelation method | Size: 233 nm; Surface Charge: + 30 mV; EE: 80% | RBC-hitchhiking for lung targeting | LPS-induced acute lung injury | [76] |
CPP-chitosan-co-PNVCL core/shell NPs | Mw: 10 kDa DD: > 95% | DOX | pH-responsive | Self-assembly of amphiphilic polymer | Size: 166 nm; PDI: < 0.45; Surface Charge: + 15.4 mV; EE: 85.3%, LC: 14.8% | (1) The amide bond between CPP and chitosan cleaved by the MMPs (2) Chitosan-mediated acidic-responsive drug release | MCF-7 tumor-bearing xenograft mice | [257] |
Chitosan-octenylsuccinic anhydride | O-carboxymethyl chitosan 12 mPa·s | γ-Fe2O3/isosorbide dinitrate | pH-responsive | Self-assembly of amphiphilic polymer | Size: 150 ~ 180 nm | Chitosan-mediated acidic-responsive drug release | H22 hepatoma cell-bearing tumor model | [66] |
Chitosan/alginate hydrogel | DD: 87 ~ 90% | Cisplatin (CDDP) and DOX | pH-responsive | Cross-linking | (DOX), EE: 83.0%, LC:86.0%; (CDDP), EE: 84.0%, LC:81.0% | Alginate-mediated swelling and chitosan-mediated acidic-responsiveness | – | [82] |
TH-302 loaded chitosan-bilirubin NPs | Mw: 3Â kDa | Hypoxia-activated prodrug (TH-302) | ROS-responsive | Self-assembly of amphiphilic polymer | Size: 116Â nm; EE: 75% | ROS-responsive hydrophobic bilirubin converted into biliverdin with improved aqueous solubility | HeLa tumor-bearing mice model | [90] |
l-serine–modified chitosan-TK-SS31 NPs | Mw: ~ 2.5 kDa | SS31 | ROS-responsive active targeting | – | – | (1) l-serine targeting to kidney injury molecule–1 (Kim-1) in kidney tubule (2) TK bond mediated ROS-responsiveness | I/R-induced AKI mice model | [258] |
Pazopanib-FA-chitosan-TK hydrogel | Mw: 150 kDa | Pazopanib AQ4N | ROS-responsive | In situ formation of hydrogel with the effects of enzyme (Laccase) | – | (1) Enzyme-mediated dimerization of FA to achieve oxygen-triggered gelation (2) TK-mediated ROS-responsiveness | 4T1 mouse breast tumor model | [92] |
PEI-ss-HECS-ss-OA micelle coated with HA | Mw: 100 kDa DD: 90% | siRNA PTX | GSH-responsive enzyme-responsive active targeting | Self-assembly of amphiphilic polymer | Size: 194 nm; PDI: 0.21; surface Charge: − 21.3 mV | (1) HA-mediated CD44 receptor targeting (2) enzyme-responsive (HAase) (3) GSH-responsive (disulfide bond) | BALB/c nude mice bearing A549 lung cancer | [84] |