Enhancing the therapeutic efficacy of adenovirus in combination with biomaterials

Abstract

With the reason that systemically administered adenovirus (Ad) is rapidly extinguished by innate/adaptive immune responses and accumulation in liver, in vivo application of the Ad vector is strictly restricted. For achieving to develop successful Ad vector systems for cancer therapy, the chemical or physical modification of Ad vectors with polymers has been generally used as a promising strategy to overcome the obstacles. With polyethylene glycol (PEG) first in order, a variety of polymers have been developed to shield the surface of therapeutic Ad vectors and well accomplished to extend circulation time in blood and reduce liver toxicity. However, although polymer-coated Ads can successfully evacuate from a series of guarding systems in vivo and locate within tumors by enhanced permeability and retention (EPR) effect, the possibility to entering into the target cell is few and far between. To endow targeting moiety to polymer-coated Ad vectors, a diversity of ligands such as tumor-homing peptides, growth factors or antibodies, have been introduced with avoiding unwanted transduction and enhancing therapeutic efficacy. Here, we will describe and classify the characteristics of the published polymers with respect to Ad vectors. Furthermore, we will also compare the properties of variable targeting ligands, which are being utilized for addressing polymer-coated Ad vectors actively.

Formulation and in vitro and in vivo evaluation of a cationic emulsion as a vehicle for improving adenoviral gene transfer

“…7). Increased adenovirus gene expression in the liver 626 and spleen has been consistently reported by other groups 627 (Kim et al, 2012;Singh et al, 2008). Twenty four hours after 628 injection with adenovirus-emulsion complex, the highest lucifer-629 ase activity was found in the lungs, followed by the spleen and liver 630 with the lowest activity measured in the heart and kidneys.…”

Evolving Lessons on Nanomaterial-Coated Viral Vectors for Local and Systemic Gene Therapy

“…Further, multiple administrations of the same viral vector can induce the production of neutralizing Abs that significantly attenuate the therapeutic efficacy of the viral vectors. To overcome rapid dissemination to nontarget tissues and antiviral immune responses, viral vectors have been encapsulated in various polymeric matrices, such as nanoparticles, microparticles, microspheres and hydrogels (Figure 1) [91][92][93][94][95][96][97][98].…”

“…Both hydrogel-and magnetic nanoparticle-mediated local delivery of viral vectors can attenuate nonspecific dissemination of viral vectors from initial injection site to nontarget tissues, resulting in superior safety profile. Cationic nanoparticle-complexed virus are internalized into the cells through distinct charge interactions between the anionic cell surface and the cationic surface of the complex, thus enabling to transduce a wide range of cells with or without primary receptor for viral uptake [97,98]. Modification of viral vectors by nanomaterials Review gel can protect viral vectors from degradative enzymes and the host immune response [101,102].…”

“…Systemic administration of viral vectors is associated with several issues, such as vector neutralization by the host immune response, short blood circulation time, ectopic gene expression in nontarget tissue and insufficient vector accumulation at the disease site, which limit their therapeutic efficacy. To address these challenges, surface modification of viral vectors with nanomaterials, such as polymers, liposomes and nanoparticles, has been widely attempted for systemic delivery of viral vectors (Figure 4) [98,[134][135][136].…”

“…The active functional group of PEG can react with the free amine of lysine within the viral capsid protein, resulting in a covalent linkage between Ad and PEG. That study showed that PEGylating 15-20% of the Ad surface [98]. Active tumor targeting: viral vectors complexed with targeting moiety-conjugated nanomaterials can be internalized into targeted cells through specific interactions between the targeting moieties and complementary receptors expressed on the surface of target cells [136].…”