Table 4.
Stimuli-activatable nanomedicine for cancer imaging/therapy in clinical trials or practices
| Stimuli | Activatable nanomedicine | Descriptions | Indications | Clinical status |
|---|---|---|---|---|
| pH | ONM-100 | Micelle covalently conjugated to indocyanine green for imaging-guided surgery | Solid tumor; peritoneal metastases; lung maliganancies | NCT03735680 (phase II, completed); NCT04950166 (phase II, recruiting); NCT05048082(phase II, completed) |
| NC-6300 | Polymer micelle with hydrazine-linked epirubicin | Advanced solid tumors or soft tissue sarcoma | NCT03168061 (phase I/II, unknown status) | |
| CRLX101 | Cyclodextrin-containing polymer with glycine-linked camptothecin | Advanced non-small cell lung cancer | NCT01380769 (phase II, completed) | |
| Redox | Mirvetuximab soravtansine | FRα-targeted antibody conjugated to maytansinoid DM4 via disulfide linker | Ovarian cancer | Approved, 2022 |
| Inotuzumab ozogamicin (Besponsa) | anti-CD22 conjugated to calicheamicin via disulfide and hydrazone linkers | Lymphoblastic leukemia | Approved, 2017 | |
| LS301 | A NIR fluorescent dye and an octapeptide that is cyclized through a disulfide bond | Breast cancer | NCT02807597 (phase I/II, recruiting) | |
| Enzyme | Brentuximab vedotin (ADCETRIS®) | AntiCD30 conjugated to MMAE via cathepsin B-cleavable linkers | lymphoma | Approved, 2011/2012 |
| Paclitaxel poliglumex (Opaxio™) | Paclitaxel polymeric NPs sensitive to cathepsin B | Head and neck cancer; glioblastoma | Approved, 2012 | |
| LiPlaCis | Liposomal formulated cisplatin sensitive to phospholipase A2 | Advanced or refractory tumors | NCT01861496 (phase I/II, completed) | |
| CX-072 | Anti-PD-L1 based on activatable Probody™ | Solid tumor; lymphoma | NCT03013491 (Phase I/II, completed) | |
| Hypoxia | 18F-FMISO | Activatable PET probe | Anaplastic glioma | NCT01200134 (phase II, completed) |
| [18F]HX4 | Activatable PET probe | Head and neck and lung cancer | NCT02976883 (phase II, completed) | |
| 18F-EF5 | Activatable PET probe | Non-small cell lung cancer | NCT01017133 (phase I, completed) | |
| Temperature | ThermoDox® | Thermosensitive liposome containing doxorubicin | Hepatocellular carcinoma | NCT02112656 (phase III, completed) |
| CriPec® docetaxel | Thermosensitive polymeric micelles containing docetaxel | Solid tumors | NCT02442531(phase I, completed) | |
| Radiation | NBTXR3 | Hafnium oxide NPs for CT and radiosensitization | LA-HNSCC; Locally advanced soft tissue sarcoma | NCT04892173 (phase III, completed); European market approval, 2019 |
| AGuIX | Polysiloxane Gd-chelates based nanoparticles for MRI and radiosensitization | Multiple brain metastases | NCT03818386 (phase II, recruiting) | |
| Magnetic field | NanoTherm® | Amino silane-coated Fe2O3 nanoparticles for MRI and MHT | Glioblastoma | Approved by EMA, 2010 |
| Magnetic nanoparticles | Magnetic thermoablation | Prostate cancer | Completed, NCT02033447 (early phase I, completed) | |
| Light | AuroLase® (AuroShell) | PEG-coated silica gold nanoshells for NIR-activated thermoablation | Head and neck cancer | NCT00848042 (not applicable, completed) |
| Photobac® | 3-(1-Butyloxy)ethyl-3-deacetyl-bacteriopurpurin-18-n-butylimide methyl ester for intracavitary PDT | Glioblastoma or gliosarcoma | NCT05363826 (phase I, recruiting) | |
| Melanin | An endogenous light-absorber | Melanoma | NCT02613325 (phase I, completed) | |
| Ultrasound | Sonazoid | Perfluorobutane gas-containing MB | Focal liver lesions | Approved (2007 in Japan and 2019 by NMPA of China) |
| Microbubbles | US-triggered MB destruction for sonoporation | Colorectal cancer hepatic metastases | NCT03458975 (phase II, completed) | |
| Optison™ | Perflutren protein-type A microspheres for US and US-triggered MB destruction | Hepatocellular Carcinoma | NCT03199274 (phase II, recruiting) |
FRα: folate receptor α; MMAE: monomethyl auristatin E; FMISO: fluoromisonidazole; LA-HNSCC: locally advanced head and neck squamous cell carcinoma; EMA: European Medicines Agency; MHT: magnetic hyperthermia therapy; NIR: near-infrared light; MB: microbubble; NMPA: national medical products administration.