TABLE 1.
The design of nano-DDS in endovascular and extravascular targeting.
| Targeting type | Nanosystem | Drugs | Targeting moieties | External stimuli | Key design features | Clinical translation | References |
| Intravascular targeting | VCAM-1–targeting polyelectrolyte micelle | miR-92a inhibitor | Inflamed ECs | Nucleotide-based therapies; polyelectrolyte complex micelles protect the nucleic acids from enzymatic degradation | None | Zhou Z. et al. (2021) | |
| VHPK-conjugated-pBAE NPs | Anti-miR-712 | Inflamed ECs | Overexpression of miR-712 leads to endothelial dysfunction and AS | None | Dosta et al. (2021) | ||
| PEG-b-PLGA copolymer-based NP | CRISPR-Cas9 plasmid DNA | Vascular ECs | NP delivery CRISPR plasmid DNA under the control of the Cdh5 promoter; genome editing in the ECs | None | Zhang X. et al. (2022) | ||
| fAuNPs | DMXAA | Tumor vessels | PTT | DMXAA enhance the local trapping of gold NPs; increased effectiveness of photothermal | None | Hong et al. (2020) | |
| RGD@HCuS(VA) | VA | ECs | NIR laser | N2 bubbles released by NIR radiation to induce tumor cell necrosis | None | Gao W. et al. (2017) | |
| Th-Dox-NPs | Thrombin and Dox | Tumor-vessel walls and tumor stroma | Active tumor tissue-targeting ability; cutting of the blood supply by thrombus and inhibiting tumor cell proliferation; synergistic treatment of embolization therapy and chemotherapy | None | Li S. et al. (2020) | ||
| Leukosomes | Inflammatory vascular | Reduced RES uptake; adhesion to inflamed endothelium | None | Martinez et al. (2018) | |||
| Leukosomes | Rapamycin | Atherosclerotic plaques | High histocompatibility; stable drug release efficiency | None | Boada et al. (2020) | ||
| RBC-membrane-camouflaged polymeric NP | Vascular | Long blood retention time | None | Hu et al. (2011) | |||
| PNP | Rapamycin | Atherosclerotic plaques | Reduce the phagocytosis of NPs by macrophages | None | Song et al. (2019) | ||
| Neutrophil cell-membrane-formed nanovesicles | Vascular inflammation | Nanovesicles can improve the specificity and affinity to the target; reduce the lung infammation and edema | None | Gao et al. (2016) | |||
| H2O2/PFP phase-change NPs | Thrombolysis | US | Oxygen release under ultrasound application | None | Jiang et al. (2020) | ||
| PHPMR NPs | MnFe2O4、 HMME、 PFP | ECs | US、SDT | High ROS production efficacy under US and SDT | None | Yao et al. (2021) | |
| SWNTs | Immune cells | PAI | Utilized PAI-active nanomaterial agents assess immune cells migration into tumors | None | Gifani et al. (2021) | ||
| Extravascular targeting | Dox/F127&P123-Tf | Dox | Tumor cells | DOX/F127&P123-Tf can inhibit cell migration and change the cell cycle | None | Soe et al. (2019) | |
| FDMCA | MIP-3β plasmid | Immune cells in tumor | Targeted gene delivery system to polarize macrophages toward M1, inhibiting tumor growth | None | He et al. (2020) | ||
| 64Cu-GE11 PMNPs | HCT116 colon cancer cells | 64Cu-GE11 PMNPs have a desirable prolonged residence time in the blood pool and a significant uptake in EGFR-expressing tumor tissue | None | Paiva et al. (2020) | |||
| TLS11a-LB@TATp-MSN/DOX | DOX | Nuclei of H22 cells | NPs contained liver cancer-specific aptamer TLS11a and nuclear localization peptide TATp to locate the nucleus | None | Ding et al. (2020) | ||
| PM@CDDP/SNP | Cisplatin and sodium nitroprusside | Tumor | PMCS selectively induced ONOO− generation after a cascade responding high levels of NOXs and GSH in tumors | None | Chen Y. et al. (2021) | ||
| Col-TNPs | ECM | Col-TNPs deliver collagenase to degrade collagen in tumors, enhancing the intracellular transcytosis of TNPs | None | Wang et al. (2022) | |||
| siFAK + CRISPR-PD-L1-LNPs | FAK siRNA, Cas9 mRNA and sgRNA | TME | Enhanced gene editing efficiency by altering the mechanical properties of the tumor microenvironment | None | Zhang et al. (2022a) | ||
| PLP–D–R | DOX and antiplatelet antibody R300 | Tumor vessels | MMP2 can promote the release of R300 in NPs, which can consume platelets and improve tumor vascular permeability | None | Li S. et al. (2017) | ||
| GE11-PDA-Pt@USPIOs | Cisplatin, poly dopamine | EGFR-positive tumor cells | MRI/PAI | The thick PAA coating allows highly efficient cisplatin; the thin PDA coating endows the particles with photo-thermal properties | None | Yang et al. (2019) | |
| PEG-TK-DOX | DOX,PhA | The tumor | PDT | The production of exogenous ROS during PDT, leading to a further ROS cascade that accelerates the release of DOX and PhA in NPs | None | Kim et al. (2020) | |
| IT-TQF NPs | IT-TQF | The tumor | PTT | First phototheranostic agent; outstanding optical and photothermal properties | None | Lou et al. (2022) | |
| MMP sensitive liposomes coated with PEG | ECM of the tumor | US | The combined use of US and microbubbles can increase the penetration depth of liposomes into the extracellular matrix | None | Olsman et al. (2020) | ||
| FCNPs | Vessels | pHIFU | pHIFU can reduce irreversible thermal effects by reducing the average intensity of US | None | You et al. (2017) | ||
| 89Zr-NRep | DOX | Tumor vessels | EP | 89Zr-NRep can be used to monitor the effects of electroporation and predict RE-mediated uptake of nanoparticle therapeutics in vivo | None | Srimathveeravalli et al. (2018) | |
| pHA-αPDL1 | α-PDL1 | Brain and the glioma | pHA-αPD-L1 can activate T cell immune response and relieve immunosuppressive TME | None | Guo et al. (2020) | ||
| TfR-targeting liposomes | Cisplatin | ECs | FUS | The use of FUS in combination with intravascular MBs can increase in BBB permeability | None | Olsman et al. (2021) | |
| PLGA-PEG NPs | Intestinal epithelium | Albumin engineered enhanced receptor binding and transcellular transport of NPs | None | Azevedo et al. (2020) | |||
| MOF-Gel NPs | Exendin-4 | Intestinal epithelium | Neutral PH encouraged sodium bicarbonate and citric acid to dissolve and reacted with CO2, thus facilitating the release of NPs from the capsules | None | Zhou Y. et al. (2021) | ||
| Polypeptide/siRNA polyplexes | siRNAs | Mucus layer and cell membrane | Fluorination of the cationic polypeptides potentiated the mucus-penetration capability; first example of transmucus gene delivery by using the fluorination approach | None | Ge et al. (2020) | ||
| Tf-AMQ NPs | AQ | NSCLC cell | Cytotoxicity studies shown reduction in IC50 values with Tf-AMQ NPs; AQ’s autophagy inhibition ability increased in Tf-AMQ NPs | None | Parvathaneni et al. (2021) | ||
| AG@MSNs-PAA | AG | OA | PAA degraded in an acidic environment, releasing AG to restore IL-1β-induced chondrocyte apoptosis | None | He et al. (2021) | ||
| BNPs | EB | Peritoneal carcinomatosis | The BNPs with abdominal tissue extended the retention after i.p. injection; EB can against multiple PTX-sensitive in vitro | None | Deng et al. (2016) | ||
| EB | Glioblastoma | NPs with ‘stealth’ properties can avoid internalization by all cell types | None | Song et al. (2017) | |||
| CPT | SCC tumor cell and matrix proteins | The encapsulation of CPT within BNPs enhanced the delivery of CPT, ; chemotherapy may be beneficial in immune suppression | None | Hu et al. (2021) | |||
| EVG | Vaginal lumen | BNPs can penetrate mucus and once in contact with epithelial cells or leukocytes, they become immobilized and are retained for long periods | None | Mohideen et al. (2017) | |||
| DES-MSNs | Skin penetration | DES-MSNs could drive the MSNs to penetrate across the entire skin via a “Drag” effect; transdermal delivery of the MSNs into blood circulation | None | Zhao et al. (2022) | |||
| CAT-TCPP/FCS NPs | CAT-TCPP | Intratumoral | SDT | Non-invasive excitation of PS in orthotropic bladder; tumor hypoxia amelioration triggered by the O2 production of tumoral endogenous H2O2 catalase | None | Li G. et al. (2020) | |
| P/B-COS NPs | BUD | Myocardium | RF | Local high temperature in RF promoted local rupture of NPs, releasing BUD | None | Liu et al. (2022) |