Recent Advances in Preclinical Research Using PAMAM Dendrimers for Cancer Gene Therapy

Abstract

Carriers of genetic material are divided into vectors of viral and non-viral origin. Viral carriers are already successfully used in experimental gene therapies, but despite advantages such as their high transfection efficiency and the wide knowledge of their practical potential, the remaining disadvantages, namely, their low capacity and complex manufacturing process, based on biological systems, are major limitations prior to their broad implementation in the clinical setting. The application of non-viral carriers in gene therapy is one of the available approaches. Poly(amidoamine) (PAMAM) dendrimers are repetitively branched, three-dimensional molecules, made of amide and amine subunits, possessing unique physiochemical properties. Surface and internal modifications improve their physicochemical properties, enabling the increase in cellular specificity and transfection efficiency and a reduction in cytotoxicity toward healthy cells. During the last 10 years of research on PAMAM dendrimers, three modification strategies have commonly been used: (1) surface modification with functional groups; (2) hybrid vector formation; (3) creation of supramolecular self-assemblies. This review describes and summarizes recent studies exploring the development of PAMAM dendrimers in anticancer gene therapies, evaluating the advantages and disadvantages of the modification approaches and the nanomedicine regulatory issues preventing their translation into the clinical setting, and highlighting important areas for further development and possible steps that seem promising in terms of development of PAMAM as a carrier of genetic material.

Nanomaterials for cancer therapy: current progress and perspectives

“…A PAMAN nanocarrier based on dendrimer was synthesized and used for chemotherapy combined with photothermal treatment of liver cancer cells. Though PAMAN dendrimers without modification have disadvantages such as low transfection efficiency, inefficient cellular internalization and instability of encapsulation [ 115 ], the nanomaterial has competitive contrast properties, showing great potential in combination therapy [ 116 ].…”

“…After endocytosis by cancer cells, encapsulated chemical drugs exert cytotoxicity or nucleic acid materials induce cell apoptosis, depending on the encapsulated cargo. Progress has been made in nucleic acid delivery and nano-DDS based on exosomes [ 72 , 78 ], PNPs, liposomes [ 208 ], dendrimers [ 115 ] are massively researched in cancer therapy.…”

Nanoparticles-Based Oligonucleotides Delivery in Cancer: Role of Zebrafish as Animal Model

“…With these aims, viral and non-viral vectors were produced. Viral carriers are widely used because of their high tolerability, standardized transfection procedures, great high and stable transfection efficiency, and high stability [ 59 , 60 ]. Other major features of viral vectors include their ability to infect specific cells through a process known as “tropism” and to transfer ONs in both dividing and non-dividing cells [ 60 ].…”

Development of Tailor-Made Dendrimer Ternary Complexes for Drug/Gene Co-Delivery in Cancer

“…Dendrimers are globular molecules, with three-dimensional structures composed by a central core with multiple repeating units covalently linked to the nucleus (referred as generations, G), a hyperbranched mantle and a corona bearing reactive functional groups. The great control over the synthesis of their architectures turns dendrimers into nanometer carriers with predictable and tailored properties [ 28 , 29 ]. Therefore, dendrimers are monodisperse and present remarkable chemical and physical stability.…”

“…Along with acting as a gene delivery vector, the well-defined core in the PAMAM dendrimer could encapsulate hydrophobic anticancer drugs or conjugate the drug on the surface [ 31 ]. PAMAM dendrimers are one of the most widely considered molecules for targeted drug and gene delivery, due to a set of favorable properties as, for instance, the possibility of core and surface groups modification, their hydrophilic nature, and the great biocompatibility [ 29 , 32 ]. Both in vitro and in vivo studies have confirmed the efficacy of PAMAM-based delivery systems to achieve the target site and release the therapeutic payload [ 33 , 34 ].…”