Table 2.
Table compiling information presented in the text on the different types of delivery strategies, tissues/cells that are being targeted with these strategies, type of cancer that is metastasizing, conventional (and other) techniques/strategies that are being assisted by nanotechnology-based approaches, and the nano-approaches that are being employed to provide added value to the other techniques
| Delivery strategy | Target | Type of cancer metastasis | Techniques that are being aided by nanotechnology | Nanotechnology approach | Refs |
|---|---|---|---|---|---|
| Primary cancer-targeting drug delivery | Tumor cells | Metastatic breast cancer and metastatic melanoma | Chemotherapy | C6 ceramide-formulated nanoliposomes | [13, 37] |
| Tumor cells | Lung cancer metastasis | Organic pharmaceutical | Podophyllotoxin (PPT) in layered double hydroxides (LDH) nano-delivery systems | [27] | |
| Tumor cells | Lung squamous carcinoma lymphatic metastasis |
Golgi trafficking miRNA/circRNA |
Lipid nanoparticle (NP) to deliver miR-671-5p | [28] | |
| Tumor cells and pre-metastasis niche | Breast tumor lung metastasis |
Anti-inflammatory and anti-thrombotic agents Surgical resection or chemotherapy |
Codelivery of anti-inflammatory and anti-thrombotic drugs with nanotherapeutic H@CaPP | [29] | |
| Tumor cells | GBM metastasis | Monoclonal antibody | Cetuximab antibody with MRI-imageable multifunctional magnetic iron-oxide NPs (IONPs) | [30] | |
| Tumor cells | Breast cancer lymphatic and lung metastasis | Chemotherapy | CD44 targeted -CBSA gold nanocluster and HA NPs (AuNC@CBSA@HA) + NO PTX and ICG-loaded NPs | [31–35] | |
| Tumor cells | Breast cancer metastasis | Tumor-homing peptide and radiation | iRGD with multistage-responsive NPs conjugated with DOX and IDD with HN shell and laser irradiation | [36] | |
| TME | Breast cancer metastasis | Radiotherapy, phototherapy and vascular disrupting agents | Vascular disrupting agent-loaded PLGA NPs (CA4-NPs) combined with temsirolimus | [41] | |
| Targeting CSCs | CSCs | Breast cancer lung metastasis | Signaling pathway inhibition | Stem cell therapy drug-carrying NPs | [47] |
| CSCs | Human small cell lung cancer metastasis | Thermo- and chemotherapy | Silica-based multifunctional magnetic NPs | [48] | |
| CSCs | Head and neck tumor metastasis | Chemotherapy | Polymeric micelle-based CDDP/m | [49] | |
| CSCs | Breast cancer metastasis | Chemotherapy | NPs co-loaded with the differentiation-inducing agent, all-trans retinoic acid, and the chemotherapeutic drug, camptothecin (CPT) | [50] | |
| CSCs | Breast cancer lung metastasis | Chemo-immunotherapy | Spatio-temporally controlled enzyme/pH dual-sensitive nano device with chemo-immuno-anti CSC therapy | [51] | |
| CSCs | Prostate cancer metastasis | Chemotherapy | Liposomes co-loaded with cabazitaxel and CSC inhibitor silibinin | [52] | |
| CSCs | GBM/solid tumor metastasis | Signaling pathway inhibition | Simultaneous administration of PEG-coated GNPs and cold plasma | [53] | |
| CSCs | Breast cancer lung and liver micrometastases | Signaling pathway inhibition | Metallofullerenol NPs containing Gd | [54] | |
| CSCs | Breast cancer/solid tumor metastasis | T-cell targeting approach | (αEpCAM/αCD3) chemically self-assembled nanorings (CSAN) prosthetic antigen receptors (PARs) | [55] | |
| Nano-immunotherapeutics | Host immune response | Breast cancer metastasis | Natural immunotherapy | Mica NPs | [56] |
| Host immune response | Breast cancer metastasis | Natural immunotherapy | preventative Selenium (Se) NPs-enriched lactobacillus | [57] | |
| TME macrophages | Melanoma and breast cancer distant metastasis | Immunotherapy | Genetically edited cell-membrane-coated magnetic NPs (gCM-MNs) | [58] | |
| Host immune response | Breast cancer lung metastasis | Immunotherapy | Nanovaccine by self-assembly of CpG-ODN and cationic polymeric NPs encapsulated with curcumin and loaded into hydrogel | [59] | |
| Host immune response | Breast cancer lung metastasis | Chemoimmunotherapy | SL@BRNP nonensemblies + iRGD peptide | [60] | |
| Host immune response | Colorectal cancer liver metastasis | Chemoimmunotherapy |
High-density lipoprotein–mimicking nanodiscs DOX/indoximod (IND)-liposome |
[61] | |
| Host immune response | Breast cancer lung metastasis | Chemoimmunotherapy | Innovative nano-enabled DOX/IND-liposome + PD-L1 antibody | [62] | |
| Host immune response | GBM metastasis | Chemoimmunotherapy | Nanodiamonds-DOX | [63] | |
| Host immune response |
Breast tumor metastasis |
Photothermal and immunotherapy | PLGA-ICG-R837 + CTLA4 | [64] | |
| Host immune response | Breast tumor liver and lung metastasis | Photothermal and immunotherapy | Polydopamine loaded with resiquimod carbon dots (PDA-PEG-R848-CD) + PD1 antibody | [65] | |
| Host immune response | Breast tumor lung metastasis | Chemo and photoimmunotherapy | Polypyrrole-loaded (CPT)-conjugated HA NP (P@CH) + anti-PD-L1 antibody | [66] | |
| Host immune response | Breast tumor lung metastasis | Photodynamic therapy + chemo-immunotherapy | pPP-mCAuNCs@HA with blood red cell membrane coating to deliver pheophorbide A, PXTK, and anti-PD-L1 peptide dPPA | [67] | |
| Host immune response | Breast tumor lung metastasis | Photodynamic therapy + chemo-immunotherapy | Ce6-loaded macrophage-mimic shape changeable NPs or chimeric micelles | [69] | |
| TME | Breast tumor metastasis | Synergistic photodynamic-immunotherapy and theranostics | Hypoxia-tropic nanoenzymes | [70] | |
| Host immune response | Breast tumor metastasis | Synergistic photodynamic-immunotherapy | Co-delivery of IDO inhibitor with photosensitizer employing redox-activated porphyrin-based liposome nanovesicle | [71] | |
| Targeting invasion/intravasation | CSCs | Cervical cancer metastasis | Chemotherapy and DNA repair | Combination treatment NQC and ADAM-17 inhibitor (GW28026) | [72] |
| Tumor cells | Breast cancer metastasis | Chemotherapy | Cathepsin B/pH dual-sensitive block copolymer conjugated with DOX and NFX to self-assemble CLM | [74] | |
| CSCs and EMT | HCC metastasis | MRI | Theranostic nanomedicine platform containing miR-125b-5p | [73] | |
| Targeting dissemination/mobility and migration | Tumor cells | Breast cancer lung metastasis | Iron chelator and chemotherapy | co-loading Dp44mT and cisplatin into intracellular drug-accumulating as-NPs | [75] |
| LNs, circulating tumor cells (CTCs) and tumor cells | Breast cancer lymph and lung metastasis | Chemotherapy | iCluster platform + chemotherapeutics | [76] | |
| CTCs | Colorectal cancer, melanoma, breast cancer | Chemotherapy | carboxylated graphene oxide (CGO) conjugated with trimethyl chitosan (TMC) and HA NPs loaded with HIF-1α-siRNA and Dinaciclib | [78] | |
| CTCs to reach metastasis site | Breast cancer lymphatic metastasis | Chemo and photothermal therapy | Drug-loaded biomimetic nanoplatelets (PMNPs) | [79] | |
| Tumor tissue/cells | Metastatic melanoma, breast cancer cells, pancreatic cancer | Cell signaling | C6 ceramide nanoliposome | [80, 81] | |
| Tumor tissue/cells | Lung cancer | Chemotherapy | LDH NPs (VP16-LDH) + Etoposide | [82] | |
| Tumor lymphatics | Lymphatic metastasis | Lymphatic spread | NPs conjugated with LyP-1 | [83] | |
| Targeting pre-metastatic niche and micrometastasis | Tumor cells and pre-metastasis niche | Breast tumor lung metastasis |
Anti-inflammatory and anti-thrombotic agents Surgical resection or chemotherapy |
codelivery of anti-inflammatory and anti-thrombotic drugs with nanotherapeutic H@CaPP | [29] |
| TME and pre-metastasis niche | Lung metastasis from postoperative breast cancer | siRNA | S100A4 siRNA conjugation with CBSA followed by exosome membrane (CBSA/siS100A4@Exosome) | [84] | |
| CSCs | Breast cancer lung and liver micrometastases | Signaling pathway inhibition | Metallofullerenol NPs containing Gd | [54] | |
| micrometastasis in vascular beds | Breast cancer metastasis | Nanottheranostic | Vascular targeting NP platform + radionuclide imaging theranostics | [85] | |
| Metastasis site-targeting drug delivery | Tumor tissue/cells | Breast cancer bone metastasis | Bisphosphonate photothermal therapy | Conjugated ZOL onto mesoporous silica NPs decorated gold nanorods (Au@MSNs-ZOL) | [86] |
| Tumor tissue/cells | Lung and breast cancer bone metastasis |
Bisphosphonate chemotherapy |
Alendronate anchored onto PAMAM dendrimer for delivery of DTX@ALN-PAMAM. Gli2; Folic acid addition onto alendronate-modified PTX-loaded PLGA NPs | [87] | |
| Tumor tissue/cells | Breast cancer brain metastasis | Gene delivery | Promelittin-mediated gene therapy employing gene delivery NPs | [90] | |
| Tumor tissue/cells | brain metastases | Small molecule | NP-drug conjugates (NDC). ultrasmall fluorescent core–shell silica NPs, Cornell prime dots (C’ dots) | [91] | |
| CTCs to reach metastasis site | Breast cancer lymphatic metastasis | Chemo and photothermal therapy | Drug-loaded biomimetic nanoplatelets (PMNPs) | [79] | |
| Tumor cells | Liver metastasis | Photodynamic and photothermal therapy | conjugated nucleus-targeting NPs (WONPs) to MSNs containing photosensitizer (Ce6) through an abnormally expressed Cathepsin B enzyme-cleavable peptide | [92] | |
| TME and pre-metastasis niche | Lung metastasis from postoperative breast cancer | siRNA | S100A4 siRNA conjugation with CBSA followed by exosome membrane (CBSA/siS100A4@Exosome) | [84] | |
| Targeting metastatic site growth/proliferation | CAFs, TME, ECM | Stroma-rich cancers such as subtypes of HCC and PDAC, and stroma-poor cancers | Receptor binding and siRNA | Surface modified nanocarriers with a cyclic peptide binding to PDGFRβ or M6P binding to IGFRII. Also, unguided nanohydrogel particles and lipoplexes loaded with siRNA | [94] |
| Hepatic stellate cells (HSC)/Cancer-associated fibroblasts (CAFs) | Stroma-rich HCC and pancreatic cancer | siRNA delivery | Unguided nanohydrogel particles and lipoplexes loaded with siRNA | [94] | |
| Tumor cells, TME | Osteosarcoma metastasis | Chemotherapy | Reduction-responsive polypeptide micelles copolymers for controlled delivery of DOX | [96] | |
| Imaging of metastases | Tumor tissue and vasculature |
Breast tumor metastasis, including brain metastasis Melanoma brain metastasis |
MRI | Multifunctional SPIO/SPION incorporating Gd. Surfactant coatings | [97–99, 103] |
| Tumor tissue and vasculature | Breast tumor liver, lung and brain metastasis | MRI and fluorescence molecular tomography | Iron oxide nanochain particles | [102] | |
| Tumor lesions | Colorectal cancer hepatic metastasis | PET | Nano-SPECT and PET tracers | [104] | |
| Tumor tissue/cells | Brain metastases | Small molecule | NP-drug conjugates (NDC). ultrasmall fluorescent core–shell silica NPs, Cornell prime dots (C’ dots) | [91] | |
| Tumor lesions | Breast cancer metastasis | PET/CT | [18F]BF4− PET/CT expressing the human sodium iodide symporter (NIS) | [106] | |
| Tumor lesions | Prostate cancer bone metastasis | Multimodal PET/MRI | inherently multimodal, all-organic 64Cu-porphysomes NPs | [107] | |
| Tumor lesions | colorectal cancer liver metastasis |
MR/X-ray photothermal therapy |
Gd-shell-coated Au nanorods | [108] | |
| Tumor cells in vasculature | Lymphatic metastasis | Multimodal imaging guided photothermal therapy | HSA-Gd-IR825 nanocomplex photothermal ablation assisted-surgery | [109] | |
| Tumor cells in vasculature | Breast cancer lymphatic metastasis | X-ray CT | HER-2 targeting theranostic W18O49 NPs | [110] | |
| Tumor tissue and vasculature | Melanoma metastasis | In vivo IR optical imaging | Highly luminescent ReANC NPs | [113] | |
| Tumor tissue | Basal human breast cancer multiorgan metastasis | Contrast-enhanced MRI, SWIR imaging | erbium-doped ReANCs Cocktail of niche-targeted probes | [114] | |
| Tumor tissue | Melanoma metastasis | Intratumoral chemotherapy, optical imaging | Albumin nanoshells targeting ligands for improved targeting of functionalized rare earth-albumin nanocomposites | [115, 116] | |
| Tumor tissue | LN micrometastasis | Image-guidance | ICG-conjugated ultra-pH sensitive polymeric micellar NPs | [117] | |
| Tumor tissue | Whole body lymphatic metastasis | Image-guidance | Iridium-based hypoxia-activated optical oxygen nanosensor, Nanobots | [118] | |
| CD44-overexpressing cancer cells and CSCs | Vasculature | Image-guidance | HA platinum nanoclusters (Pt NCs) | [119] | |
| Tumor tissue and vasculature | Breast cancer lung metastasis | Radionuclide imaging | 99mTc radio-labeled dual-ligand NPs | [120] | |
| Vasculature | Breast cancer lung metastasis | Radionuclide imaging | GNPs labeled with 99mTC and a αvβ3 targeting ligand | [85] |
NP nanoparticle, CSCs cancer stem cells, HCC hepatocellular carcinoma, TME tumor microenvironment, LNs lymph nodes, CTCs circulating tumor cells