. Author manuscript; available in PMC: 2018 Dec 11.

Published in final edited form as: Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2015 Jul 7;8(2):208–222. doi: 10.1002/wnan.1358

TABLE 1.

Combination Nanocarriers

Drug combination	Liposomal nanocarrier	Author	Year	Significance	Mechanism
Paclitaxel + Epigallocatechin⁵⁸	PC:Cholesterol	Ramadass, S.	2015	Compared to treatment with either PTX or EGCG alone, PTX/EGCG combination treatment significantly reduced cellular viability, increased apoptosis, and decreased expression of MMP-2 and MMP-9 in MDA-MB-231 cells in vitro.	PTX inhibits the cell cycle through microtubule stabilization; EGCG inhibits matrix metalloproteinases.
Cytarabine + Daunorubicin⁵⁹	CPX-351 (5–20 mol% Cholesterol)	Lancet, J.	2014	Increased response rate (complete + incomplete remissions) by 15.5% in patients with AML. Provided rationale for a phase 3 clinical trial.	Nanoliposomal encapsulation allows the optimal molar ratio of drugs (5:1) to be maintained during delivery.
Doxorubicin + Omacetaxine Mepesuccinate⁶⁰	PG:PC:Cholesterol	Shim, G.	2014	Compared to untreated mice, the combination liposome resulted in a 98.5% reduction in tumor volume on day 35 and a 97.3% reduction on day 45 after treatment.	OMT decreases MCL1 levels, DOX inhibits topoisomerase II. MCL1 is an anti-apoptotic protein that, when inhibited in combination with DOX, has been shown to increase anti-cancer effects
Doxorubicin + Topotecan⁶¹	DSPC:Cholesterol	Patankar, N.	2013	Mean survival time of mice receiving the combination therapy increased from 18 days (untreated) or 40 days (Topotecan) to 52 days.	Topotecan inhibits topoisomerase I, DOX inhibits topoisomerase II.
Irinotecan + Doxorubicin⁶²	DSPC:Cholesterol	Shaikh, I.	2013	Combo treatment resulted in a mean survival time of 52 days in ovarian tumor-bearing SCID mice, compared to 27 days with saline treatment. Encapsulation increased the mean residence time in the plasma 27-fold (DOX) or 28-fold (irinotecan).	Allowed the synergistic molar ratio of 1:1 to be kept during delivery. Used Mn²⁺ and pH gradients to load both drugs and reported >80% loading efficiency.
Irinotecan + Fluoroorotic Acid²⁷	DSPC:Cholesterol: mPEG-DSPE	Reviere, K.	2011	Combo treatment provided statistically significant differences in antitumor effects in vivo than single drug-loaded liposomes.	Irinotecan inhibits topoisomerase I, fluoroorotic acid inhibits DNA and RNA synthesis via inhibition of thymidylate synthase.
Irinotecan + Floxuridine⁶³	CPX-1 (5–20 mol% Cholesterol)	Batist, G.	2009	Phase I study of liposome combination therapy, ‘first clinical evaluation of fixed drug ratio dosing designed to maintain synergistic molar ratios for enhanced therapeutic benefit’.	Irinotecan and floxuridine are standard combination chemotherapies. Floxuridine inhibits DNA and RNA synthesis via inhibition of thymidylate synthase, irinotecan inhibits topoisomerase I.
C6 Ceramide + Sorafenib⁶⁴	C6 ceramide- containing liposome	Tran, M.	2008	A 30% increase in tumor inhibition in vivo (compared to sorafenib alone) and a 58% increase in tumor inhibition (compared to ceramide nanoliposome alone) occurred. Provided foundation for clinical trials.	Treatment with the combo liposome synergistically inhibited cultured cells by cooperatively targeting mitogen-activated protein kinase and phosphatidylinositol 3-kinase signaling