Table 2.

Preclinical and clinical studies involved in combinational therapy for inhibiting various stages of MDR cancers.

Type of Cancer	siRNA	Nanoparticle	In Vitro	In Vivo	Clinical Trails	Hallmark Modulation	Reference
Lung Cancer	MRP1 + BCL2	Cationic lipids - DOTMA and N-[1-(2,3-dioleoyloxy) N,N,N-trimethylammonium methylsulfate (DOTAP)	H69AR cell line,MCF-7/ AD cell line, andHCT15 cell line.			Metastasis	140
	MRP1 + BCL2	Pyridylthiolterminated MSN, as an inhalation delivery	None	A549 cell line, Tumor (A549)-bearingnude mice	Phase 1	Invasion	135
Prostate Cancer	TRIM24 gene-specific siRNA	Nanocarrier system based on humanmonoclonal prostate-specific membrane antigen-antibody (PSMAab) for targeted delivery of tripartiteMotif-containing 24 (TRIM24)-siRNA.	PSMA + CRPC cells.			Invasion	105
	GRP-78 specific siRNA;	Calcium phosphate core, dioleoyl phosphatidic acid, and arginine-glycine-aspartic acid peptide-modified polyethylene glycol, for co-delivery of the78-kDa glucose-regulated protein (GRP78)-specific siRNA and docetaxel as a combination therapy.	PC3-CRPC	PC3-CRPC		Metastasis	141
	Si-TWIST (si419 and si494), a developmental transcription factor that leads to chemotherapic resistance and cancer cell stemness.	Amphiphilic PAMAM dendrimer YTZ3-15 or polyethyleneimine (PEI) coatedmesoporous silica nanoparticle (MSN)		A2780R and Ovcar8 cells; mice treated		Metastasis	128, 142, 143
Breast Cancer	P-gp and VEGF-specific siRNA	Selenium/ruthenium-MOF nanoparticles		MCF-7/T cell; nude mice		Invasion and metastasis	144, 145