Table 1.
Challenges of targeting CTCs by nanomedicine.
| CTC properties | Practical consequences | Refs. |
|---|---|---|
| Rarity of CTCs: a needle in a haystack problem | Low efficiency of targeting CTCs | 5,47 |
| Heterogeneous subpopulations | Mesenchymal CTCs are not recognized by nanomedicine targeting epithelial cell markers such as EpCAM; Necessity of killing all CTCs vs. MICs or CSCs in the circulation; Differential drug resistance among different subpopulations | 73,78,149,161 |
| Formation of CTC clusters | Increased invasiveness, resistance to anoikis and trapping in microvessels | 1,24,46,66,163 |
| Short circulation time of CTCs | Limited exposure time to therapeutics against CTCs in circulation | 93,125,135 |
| Shielding of CTCs by platelets | Physical barrier to penetration of nanomedicine into CTCs; pro-metastatic role via induction of EMT, establishment of early metastatic niches, pro-survival signaling etc. | 35,74,75 |
| Off-target effects associated with systemic drug delivery | Systemic cytotoxicity | 136,162 |