Membrane/Core Nanoparticles for Delivery of Therapeutic Nucleic Acid - Nanotechnology for the Delivery of Therapeutic Nucleic Acids - page 71

This observation has been further confirmed by the z-axis images
of each formulation, where a majority of siRNA in the non-targeted
NPs formulation remained in the extracellular space but most of the
siRNA in the targeted NPs was internalized into the cells.
One of the widely used targeting ligands for gene delivery to
cancer is monoclonal antibody. GC4 single-chain variable fragment
(scFv), a tumor-targeting human monoclonal antibody,

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has
several advantages as a target ligand, such as its high specificity,
strong affinity, profound penetration into the tumor site, and

a low antigenicity. Due to these beneficial characteristics of GC4
scFv, it has been used as a targeting ligand in modified LPD NPs
(LPH, Liposome-polycation-hyaluronic acid) for the delivery of
siRNA and miRNA to a B16F10 lung metastasis mouse model. The
GC4 scFv-targeted NPs showed a significant intracellular delivery of
siRNA to the tumor tissue and a reduced uptake in the liver and the
kidney compared to free siRNA. This indicates that the high delivery
efficiency of siRNA or miRNA into the B16F10 lung metastasis mouse
is from the tumor-targeting scFv ligand. According to previous
studies using targeting ligands, the alteration of intratumoral
distribution and increased tumor cell uptake of NPs have been found
when tumor-specific ligands, such as anisamide and GC4 scFv, are
incorporated into the NPs. Furthermore, the uptake of NPs in tumors
may not ultimately be increased when these tumor-specific ligands
are not used.

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3.4.1.3 Therapeutic applications of LPD
3.4.1.3.1 Survivin siRNA
Survivin, a 16.5 kDa protein with a single BIR domain, is a
member of the inhibitor of apoptosis protein (IAP) family (XIAP,
cIAP1, cIAP2, and survivin), which is expressed in human cancer
cells.

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It is a nuclear cytoplasm shuttling protein and is known
to inhibit apoptosis and regulate the cell cycle. Overexpression
of survivin may lead to an unfavorable progression of disease,
development of resistance to chemotherapy as well as radiotherapy,
or decreased survival rates in non-small cell lung cancer (NSCLC)
patients. Therefore, survivin has been intensively utilized as

a prognostic marker or potential target for lung cancer treatment.
The survivin gene silencing effects of different siRNA formulations
were determined in NCI-1299, sigma receptor-expressing cells.

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