Table 3.
Strategies for targeted delivery of small molecule drugs/biologics to ovarian cancers by US mediation.
| Name | Delivery system | OCs assessed | OT models used | Advantages/lacuna |
|---|---|---|---|---|
| CEA | PTX-loaded phase-shifting PLGA nanoparticles with PFP (PTX-PLGA-SA/PFPs) |
SKOV3 | – | Suitable for killing OCs at early stage. Suitability for attenuating metastatic OCs not studied. |
| LHRHa | FITC-labeled LHRH-a/CPT-11/PLGA microspheres PTX-loaded anti-LHRH receptor targeted phase-transformation lipid nanoparticles Lipid MBs conjugated with LHRHa via an avidin-biotin linkage and mixed with the pEGFO-N1-wtp53 plasmid LHRHa-targeting PTX-loaded lipid MBs via avidin-biotin conjugation Lipid MBs bind to LHRHa targeting survivin shRNA via avidin-biotin conjugation Lipid MBs bind to LHRHa targeting livin shRNA via avidin-biotin conjugation |
A2780/DDP A2780 & OVCAR3 A2780/DDP A2780/DDP A2780/DDP OVCA-433 |
Balb/c xenotransplanted with A2780/DDP Balb/c xenografted with OVCAR3 - Nude mice xenografted with A2780/DDP Nude mice xenografted with A2780/DDP - |
Suitable for killing OCs at the primary site as well as highly invasive types. The efficacy in metastatic condition has not been assessed. |
| FAR | FA surface-conjugated US-activable with PFP in the core and HMME in the phospholipid shell FA surface-conjugated nonocage with curcumin, ferritin and PFH in the core (stimulation by LIFU) HCPT containing NDs with FA in the surface and Fe3O4 and PFP in the core (stimulation by LIFU) FA-lipid-PLGA nanoparticle containing SIK2 siRNA and antisense miR21 in a layer-by- layer structure to protect RNAs from degradation miR-34a-mimic-FA-MBs (stimulation SKOV3 by UTMD) |
SKOV3 SKOV3 SKOV3 OVCAR3, A2780, and SKOV3 |
Nude mice xenografted with SKOV3 Nude mice xenografted with SKOV3 Nude mice xenografted with SKOV3 Nude mice xenografted with OVCAR3 |
Suitable for killing OCs at the primary site. Suitability for attenuating metastatic OCs not studied. |
| CSC | Apoptosis induction and stemness reduction by LIUS GSH-responsive PSP@MB for sonoporation and endocytosis of ALDH1 shRNA in CSCs |
CSCs from OVCAR5 and A2780 CSCs (ALDH1+ & CD133+) from fresh human ovarian tumor cells |
Cis+LIUS reduced CD133+ cells in OVCAR5 and A2780 cell-harboring xenograft mice Primary human ovarian tumor cells xenografted into female NOD.SCID mice |
Killed specific subpopulation of ovarian CSCs and suppressed ovarian tumor growth. Efficacy in preventing relapse not studied. |
| Angiogenesis | VEGF siRNA-complexed ABP was then combined with US for activating MBs | A2780 | Nude mice xenografted with A2780 | Effective in killing OCs at the primary site. Anti-metastatic potential not assessed. |
| Hypoxia | PFC (artificial oxygen carrier) loaded in lipid MBs for US-mediated therapy [(PTX/ICG) and oxygen-loaded PLGA nanoparticles PIO_NPs]; PFP core for carrying oxygen and a PLGA shell ICG and PTX |
PTX-resistant SKOV3 SKOV3 |
Nude mice xenografted with SKOV3 Nude mice xenografted with SKOV3 |
Effective in killing drug-resistant OCs and likely suitable for killing CSCs. |
| Immunogenic cell death | NPs loaded with oxaliplatin ICG (a photo-/sonosensitizer), and PFP (that undergoes phase transition under US treatment) | Syngenic mice xenografted with ID8 tumor cells | Induction of strong cytotoxic T cell response to murine tumor cells. ICD in human OCs has not been assessed. |
CEA, Carcinoembryonic antigen; LHRHa, leutinizing hormone releasing-hormone agonist; FAR, folic acid receptor; CSC, cancer stem cell; ALDH1, aldehyde dehydrogenase 1; ABP, arginine-grafted bioreducible polymer; PTX, paclitaxel; Cis, cisplatin; PFP, perfluoro-n-pentane; PIO_NPs, PTX/ICG and oxygen loaded PLGA nanoparticles; LIUS, low intensity ultrasound.