Table 2.
Preclinical nanoparticle delivery systems in MM.
| Type | Formulation | Drug | In vitro efficacy | In vivo efficacy | Biodistribution/ Toxicity | Ref. |
|---|---|---|---|---|---|---|
| Non- targeted | Liposome | Bortezomib | Proteasome inhibition, induction of apoptosis, and cytotoxicity | Dose: 1 mg/kg twice i.v. Tumor growth inhibition | Reduced body weight loss No biodistribution | Ashley, J.D., et al., J Med Chem, 2014. 57(12): p. 5282-92. |
| Anti-estrogens | N/A | Dose: 12 mg/kg/week i.v. Tumor growth inhibition | N/A | Maillard, S., et al., J Steroid Biochem Mol Biol, 2005. 94(1-3): p. 111-21. | ||
| Polymeric NPs (PLGA-PEG) | Thymoquinone | Anti-proliferative effect | N/A | N/A | Ravindran, J., et al., Biochem Pharmacol, 2010. 79(11): p. 1640-7 | |
| Polymeric NPs (Chitosan) | Camptothecin | Cytotoxicity | Dose: 2.5 mg/kg thrice i.v. Tumor growth inhibition and PST | N/A | Li, Z., et al., Oncol Rep, 2012. 27(4): p. 1035-40 | |
| Micelles | Carfilzomib | Improved stability and cytotoxicity | N/A | N/A | Ao, L., et al., J Pharmacol Exp Ther, 2015. 355(2): p. 168- 73. | |
| Inorganic NPs (Silica) | Snake venom from Walterinnesia aegyptia | Induction of apoptosis, and cytotoxicity | Dose: 1 μg/kg/day s.c. in the tumor site Enhanced anticancer efficacy | N/A | Sayed, D., et al., Oxid Med Cell Longev, 2012. p. 386286. Al-Sadoon, M.K., et al., Cell Immunol, 2013. 284(1-2): p. 129-38. | |
| Inorganic NPs (Iron oxide) | Placitaxel | Identification of CD138- CD34- tumor stem cells | Dose: 0.6 - 2 mg/kg once a week for 2 weeks Tumor growth inhibition of CD138- CD34- tumor stem-like cells | N/A | Yang, C., et al., Int J Nanomedicine, 2013. 8: p. 1439-49. | |
| Triggered | Magnetic NPs | Doxorubicin | N/A | Dose: 0.13 mg/kg + magnetic field Tumor growth inhibition | No significance toxicity No biodistribution | Hayashi, K., et al., Theranostics, 2014. 4(8): p. 834-44. |
| Targeted | VLA-4 | Doxorubicin | Induction of cytotoxicity and apoptosis, overcame CAM-DR | Dose: 6 mg/kg thrice Tumor growth inhibition and higher accumulation in the tumor | Reduced body weight loss | Kiziltepe, T., et al., Blood Cancer J, 2012. 2(4): p. e64 |
| Carfilzomib | Induction of apoptosis and cytotoxicity | Dose: 5 mg/kg twice a week i.v. Tumor growth inhibition and higher accumulation at the tumor | Reduced body weight loss | Ashley, J.D., et al., J Control Release, 2014. 196: p. 113-21 | ||
| MYC inhibitor | Induction of apoptosis and cytotoxicity | Dose: 0.145 mg/ml thrice a week i.v. Survival benefits | N/A | Soodgupta, D., et al., Mol Cancer Ther, 2015. 14(6): p. 1286- 94 | ||
| ABC drug transporters | Placitaxel | Inhibition of CD138- CD34- tumor stem-like cells growth | Dose: 10 μg mAb and 8 μg placitaxel for 4 weeks Tumor growth inhibition and PST in CSC models | Lower toxic side effects | Yang, C., et al.,Nanomedicine, 2014. 9(1): p. 45-60. & J Biomed Nanotechnol, 2014. 10(2): p. 336-44. | |
| Bone micro- environment | Bortezomib | Targeted NPs presented good binding, and induction of apoptosis | Dose: 0.5 mg/kg twice a week i.p. Tumor growth inhibition and PST | Biodistribution by imaging No side effects studies | Swami, A., et al., Proc Natl Acad Sci U S A, 2014. 111 (28): p. 10287-92 |
Legend: NPs, Nanoparticles; N/A, Not available; i.v., intravenous; s.c., subcutaneous; i.t., intratumoral; i.p., intraperitoneal; PST, prolonged survival time; CAM-DR, cell adhesion mediated drug-resistance; ABC, ATP-binding cassette; CSC, cancer stem cells.