TABLE 1.
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.