Table 3.

Smart nanocarriers developed and tested in in vitro and in vivo models of breast cancer.

Type of responsive nanocarrier	Nanoparticulate system	Therapeutic moiety delivered	In vitro effects	In vivo effects	Ref.
pH and redox responsive	Mesoporous silica nanoparticles	Bcl-2 siRNA and DOX	pH and redox responsive drug release and enhanced uptake due to the folate modification, silenced the expression of Bcl-2 therefore exhibiting cytotoxic and apoptotic activities in MDA-MB-231 cells	–	[182]
Acid responsive	Polymeric nanoparticle	NgBR siRNA	Appearance of positive surface charge due to acid mediated discarding of DMMA which aided in the better siRNA uptake and supressed the NgBR expression.	The nanosystem suppressed the distant metastasis through inhibiting epithelial-mesenchymal transition and normalizing the blood vessels in 4T1 tumor bearing BALB/C nude mice	[183]
Enzyme and pH responsive	Polymeric nanoparticle	Anti-luciferase siRNA	Polymeric NPs depicted a 2.5-fold increase in the cellular internalization in the presence of MMP-7, and increase in hemolysis at pH <6.2. Enhanced luciferase knockdown R221A-Luc mammary tumor cells	–	[184]
Acid responsive	Core-shell nanoparticles	MnSOD siRNA	Greater cellular apoptosis and MnSOD expression silencing was observed in TAM-resistant MCF7-BK-TR breast cancer cells by core-shell acid responsive NPs	Reversal of TAM-resistance to apoptosis, the scrambled siRNA transplanted tumors exhibited five-times larger size than MnSOD siRNA transplanted tumors in nude mice.	[172]
pH responsive	Triple layer micelle plex	siRNA-p65 and cisplatin prodrug	150 nM concentration of siRNA-p65 about 50% of the p65 which further inhibited the MMP-9 and down regulated 70% of cyclin D1 in 4T1 cells. Further, 4.4- and 1.5-fold decline in the migration and invasion capability and inhibition of NF-κB pathway respectively was demonstrated.	The triple layer micelle plex blocked the primary tumor growth as well as the metastasis to lungs in vivo	[185]
Enzyme responsive	Cascaded targeting nanoparticles	siRNA and DOX	In MDA-MB-231 cells, elevated cytotoxicity was observed due to the knockdown of Bcl-xL and breaking the CTGF-mediated resistance to apoptosis which is induced by DOX	The nanoparticles treated animal group shown a significant suppression of Bcl-xL, cIAP1 and CTGF levels and inhibited the tumor cell division and proliferation.	[186]