Nanocarriers in advanced drug targeting: setting novel paradigm in cancer therapeutics

Figures & data

Figure 1. Engineered NP depicting various ligands for conjugation to NP surface through linker.

Figure 2. Drug targeting mode of active and passive therapy to cancer cells. In healthy tissues, cells are well-organized, endothelial cells showing no leaky vasculature, whereas in the tumour, tissues cells are disorganized endothelial cells showing leaky vasculature through which nanocarriers squeezes out. Non-targeted NPs or passively targeted NPs show enhance permeation and retention (EPR) effect (not shown in the diagram) and targeted NPs across tumor tissues show receptor mediated endocytosis.

Figure 3. Various nanocarriers used in advance drug targeting.

Table 1. Some example of drug nanocarriers along with transport mode across cell membrane with therapeutic outcomes.

Active moiety	Nanocarrier	Targeting/ligand	Cell line	Therapeutic outcomes	Ref.
Cisplatin	Silica nanoparticle	Active targeting approach	Colon cancer cell line	Silica nanoparticles was 20 times potent than plain cisplatin	[40]
Aminolevulinic acid	Calcium fluoride-coated up-conversion nanoparticle	-Do-	–	Valuable in vitro and in vivo study. Deeper penetration of nanoparticles. It also has application in bio-photonic and photonic system	[41]
–	Immunoliposomes	-Do-, VCAM-1	Human Colo 677 tumour xenograft	Biodistribution studies showed higher tumour accumulation and altered endothelial function	[42]
Docetaxel	Carbon nanotube	-Do-	Murine S180 and PC3 cell line	Higher in vitro and preclinical efficacy in murine S180 and PC3 cell line cancer model compared to free Docetaxel	[43]
Paclitaxel	Functionalized micelles	Active targeting on CD44-receptor	Breast cancer cell line, MCF-7 cells	High rate of growth inhibition in breast cancer cell line, MCF-7 cells	[31]
Doxorubicin	PEG/TPGS-mixed micelles	P-glycoprotein-mediated active transport	Resistant ovarian MDR cancer-cell lines	Enhanced in vitro cytotoxicity, drug uptake, and apoptosis for drug resistant H460/TaxR cancer cells	[44]
Gemcitabine	PEG-DSPE/TPGS-mixed micelles	Cellular internalization via endocytosis	Cancer BxPC-3 xenografts model	Formulation showed the high circulation time of gemcitabine and anti-tumour efficacy three-fold higher antitumor efficacy in mice	[25]
Doxorubicin	Micelle-based nanoparticles	Passive transport of drug	CD133+ P388 cell line	Reduced tumorigenicity cancer formation frequency and aggressiveness in vivo and diminishes breast cancer resistant protein overexpression. DNA methylation also changes which leads to more sensitive anti-tumour therapy against MDR cancer cells	[45]
Doxorubicin	Chondroitin sulphate A-nanoparticle	Both passive and active strategies involve in tumour target	Human breast adenocarcinoma MDA-MB-231 cells	CD44 receptor mediated tumour targetability appeared in vivo	[46]
Lactoferrin	Aptamers- Fe3O4-saturated lactoferrin (Fe3O4-bLf) nanocarriers with locked nucleic acid	Active transport	Xenograft colon cancer model (EpCAM, CD133, CD44)	Induce apoptosis, complete regression of tumour was observed in 70 % of mice	[47]
Gold NPs	PEGylated AuNPs decorated with transferrin	Receptor-mediated endocytosis	Neuro2A cells-bearing mice	Optimized drug release, better therapeutic action and limited non-specific transport to normal cells	[24]
shRNA	CD44-targeted shRNA delivered by PLGA-based NPs	Active transport	Human ovarian SKOV-3 cells	Inhibition of angiogenesis, proliferation of cells and the induction of apoptosis	[48]
shRNA	Jet PEI-based NPs with CXCR4 shRNA	-Do-	Melanoma	Decreased expression of CXCR4 mRNA, inhibition of pulmonary metastasis of melanoma cells	[49]
Salinomycin	PEGylated PLGA nanoparticles	CD133; aptamer, receptor-mediated endocytosis	–	Osteosarcoma	[50]
Doxorubicin	Folate-terminated polyrotaxanes and dequalinium	Folate-mediated endocytosis	Doxorubicin-resistant MCF-7 breast cancer cells and MCF-7/Adr xenografts in nude mice	Six-fold increase of DOX intracellular uptake and decreased drug efflux for functional nanocarriers when compare to the free compounds	[51]

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