Table 4.

Immunodeficient mouse strains and their applications for nanomedicine evaluation. Code: +++ immune components present, + residual components, and - absent components in each model.

Model	Immunological Profile	Innate components	Adaptative components	Applications	Examples of Tested Nanomedicines.
NUDE	Foxn1nu mutation. Athymic and T cell-deficient. Intact innate immunity.	C5 complement +++ Macrophages +++ Granulocytes +++ Natural killer cells +++	Dendritic cells+++ Antibodies +++ B cells+ T cells-	Engraftment of cancer cell lines. Easy evaluation of tumor growth. Not suitable for primary cells	Doxil® [149]
RAG	Rag deficient. T and B cells depleted. Intact innate immunity.	C5 complement +++ Macrophages +++ Granulocytes +++ Natural killer cells +	Dendritic cells+++ Antibodies- B cells- T cells-	Most commonly used genetic background. Radiation tolerant. Poor host for primary cells.	–
SCID	Prkdcscid mutation. T and B cells depleted. Intact innate immunity.	C5 complement +++ Macrophages +++ Granulocytes +++ Natural killer cells +++	Dendritic cells+++ Antibodies- B cells- T cells-	Engrafts hematopoietic cancer cells and some primary cells. NK activity limits engraftment. Poor radiation tolerance.	Ag/Au bimetallic nanoparticles [168]
NOD-SCID	Lacks mature B and T cells. Reduced innate immunity.	C5 complement- Macrophages+ Granulocytes+++ Natural killer cells+	Dendritic cells+++ Antibodies- B cells- T cells-	Engrafts hematopoietic cancer cells and some primary cells. Residual natural killer cell activity limits engraftment. Poor radiation tolerance.	Polymeric micelles loaded with Zileuton® [169]
NOG	NOD-SCID mice crossed with IL2γ receptor null mice resulted from a truncation of the intracellular signaling domain in the NOD/ShiJic-Prkdcscid mouse. The receptors can bind cytokines IL-2, 4, 7, 9, 15, and 21 but do not become active. Lacks mature B and T cells. Impaired innate immunity.	C5 complement- Macrophages+ Granulocytes+++ Natural killer cells-	DC+ Antibodies- B cells- T cells-	Enhanced engraftment of primary cells, tissues, and tumors. Efficient host for human hematopoiesis and immunity. Optimal strain for humanized models. Permits long-term experiments. Poor radiation tolerance.	–
NSG	NOD-SCID mice crossed with IL2γ receptor null mice resulted from a complete null mutation in the NOD/ShiLtSz-Prkdcscid mouse. Complete knockout of receptors for cytokines IL-2, 4, 7, 9, 15, and 21. Lacks mature B and T cells. Impaired innate immunity.	C5 complement- Macrophages+ Granulocytes+++ Natural killer cells-	DC+ Antibodies- B cells- T cells-	Enhanced engraftment of primary cells, tissues, and tumors. Efficient host for human hematopoiesis and immunity. Optimal strain for humanized models. Permits long-term experiments. Poor radiation tolerance.	Titanium dioxide, silica, and gold nanoparticles. [167]

Abbreviations: dendritic cells (DC), natural killer (NK), athymic nude (Nude), severe combined immunodeficiency (SCID), non-obese diabetic severe combined immunodeficiency (NOD-SCID), Rag-deficient (RAG), NOD/Shi-scid/γc^−/− null (NOG) and NOD/SCID/γc^−/− (NSG) strains.