An Adenoviral Platform for Selective Self‐Assembly and Targeted Delivery of Nanoparticles

Abstract

Metallic nanoparticles (NPs) can be used for the diagnosis, imaging, and therapy of tumors and cardiovascular disease. However, targeted delivery of NPs to specific cells remains a major limitation for clinical realization of these potential treatment options. Herein, a novel strategy for the specific coupling of NPs to a targeted adenoviral (Ad) platform to deliver NPs to specific cells is defined. Genetic manipulation of the gene-therapy vector is combined with a specific chemical coupling strategy. In particular, a high-affinity interaction between a sequence of six-histidine amino acid residues genetically incorporated into Ad capsid proteins and nickel(II) nitrilotriacetic acid on the surface of gold NPs is employed. The selective self-assembly of gold NPs and Ad vectors into multifunctional platforms does not negatively affect the targeting of Ad to specific cells. This opens the possibility of using Ad vectors for targeted NP delivery, thereby providing a new type of combinatorial approach for the treatment of diseases that involves both nanotechnology and gene therapy.

Synthetic biology devices for in vitro and in vivo diagnostics

“…The targeted delivery of genetically encoded tools is a challenge that surpasses that of drug delivery because the cargo needs to reach its destination and undergo expression. One of the earliest and still major strategies used for delivery involves virus-based vectors, including retroviruses, adenoviruses, and adeno-associated viruses, which have been modified to carry engineered payloads and cell-targeting elements (79,80). Self-assembled virus-like particles (VLPs) and virosomes (virion-like phospholipid bilayer vesicles with surface glycoproteins) can also carry biomolecular cargo (81,82).…”

Current advances in adenovirus nanocomplexes: more specificity and less immunogenicity

“…With the development of diverse carrier designs and materials, Ad nanocomplexes have evolved into potent cancer therapeutics tools (48), gene delivery systems (2), and imaging agents (17,49). The therapeutic effects of these versatile novel Ad nanocomplexes should be characterized in vivo in order to validate their practical potential in a clinical setting.…”

Limitations of Adenoviral Vector-Mediated Delivery of Gold Nanoparticles to Tumors for Hyperthermia Induction

“…In previously published reports [17, 18], we have coupled AuNPs of 1.3 and 1.8 nm diameter to Ad vectors to demonstrate the principle of coupling metal NPs to gene therapy vectors that could potentially facilitate combination therapy of neoplastic disease. Various types and sizes of AuNPs have been used for hyperthermic tumor cell killing by several groups [2-5, 7].…”

“…Based on this, we have previously proposed to combine nanotechnology-based treatment opportunities with gene therapy for developing novel multifunctional nanoparticles for tumor treatment [16]. To this end, we have combined together two independent therapeutic modalities into a single nano agent for tumor treatment by coupling AuNPs to Ad vectors without perturbing the biological interactions of Ad vectors with target cells [17, 18]. The AuNP-coupled Ad vector nano agent could be used to explore the possibility of combining gene therapy with AuNP based hyperthermia for the treatment of cancer [17, 18].…”

“…To this end, we have combined together two independent therapeutic modalities into a single nano agent for tumor treatment by coupling AuNPs to Ad vectors without perturbing the biological interactions of Ad vectors with target cells [17, 18]. The AuNP-coupled Ad vector nano agent could be used to explore the possibility of combining gene therapy with AuNP based hyperthermia for the treatment of cancer [17, 18]. In the current study, we tested the feasibility of utilizing these AuNP-coupled Ad vectors for hyperthermia therapy.…”