TABLE 1.

The application of nanoparticle-based drug delivery system for overcoming drug resistance.

Targeted pathway	Mechanisms (in addition to antitumor efficiency)	Drugs	References
Efflux transporters	Bypass efflux transporters	NP itself	(Murakami et al., 2011)
	Inhibit efflux transporters	COX-2 inhibitors	(Zhang S. et al., 2019)
		P-gp-targeted siRNA	(Patil et al., 2010; Navarro et al., 2012)
		miRNA-495	(He et al., 2019)
Apoptosis	Inhibit anti-apoptosis pathway	Bcl-2-targeted siRNA	(Wang et al., 2006; Saad et al., 2008; Chen et al., 2009; Choi et al., 2019)
		NF-κB inhibitors (pyrrolidine dithiocarbamate/curcumin)	(Fan et al., 2010; Misra and Sahoo, 2011; Zhao et al., 2019)
	Activate pro-apoptosis pathway	Ceramide	(Devalapally et al., 2007; van Vlerken et al., 2010)
		p53 gene therapy	(Prabha and Labhasetwar, 2004; Choi et al., 2008)
Efflux transporters and apoptosis	Inhibit efflux transporter expression meanwhile promoting apoptosis through down-regulation of Bcl-2 and NF-κB expression	Bcl-2 convertor gene-loaded NPs	(Cheng et al., 2018)
		Resveratrol	(Zhao et al., 2016; Singh et al., 2018)
	Inhibit efflux transporters and promote apoptosis by inducing mitochondrial outer membrane permeabilization	Mitochondria-targeted NPs	(Wang et al., 2020)
Hypoxia	Silence the HIF-1α gene	HIF-1α siRNA	(Zhao et al., 2015; Luan et al., 2018; Hajizadeh et al., 2020)
	Inhibit the function of HIF-1α	HIF-1α inhibitors	(Reddy et al., 2011)
	Indirectly downregulate HIF-1α expression	Inhibitors of the PI3K/Akt/mtor pathway	(Zhang et al., 2018)
		HSP90 inhibitors	(Long et al., 2018)

Abbreviations: Bcl-2 = B cell lymphoma-2; COX-2 = cyclooxygenase 2; HIF-1α = hypoxia-inducible factor 1α; HSP90 = heat shock protein 90; NF-κB = nuclear factor kappa B; NPs = nanoparticles; P-gp = P-glycoprotein; PI3K = phosphoinositol-3-kinase; siRNA = small interfering RNA.