From Polydeoxyribonucleotides (PDRNs) to Polynucleotides (PNs): Bridging the Gap Between Scientific Definitions, Molecular Insights, and Clinical Applications of Multifunctional Biomolecules

Abstract

Polydeoxyribonucleotides (PDRNs) and polynucleotides (PNs) are similar DNA-derived biopolymers that have garnered significant scientific attention since the 1990s for their potential applications in wound healing and skin rejuvenation. These biopolymers exhibit a broad molecular weight (MW) range, typically spanning from 50 to 1500 kDa. However, recent studies have expanded this range to encompass fragments as small as 1 kDa and as large as 10,000 kDa. Clinically, PDRN/PN formulations, commercially available in various galenic forms (gels, creams, serums, masks, and injectables), have demonstrated promising effects in significantly promoting skin regeneration, reducing inflammation, improving skin texture, preventing scar formation, and mitigating wrinkles. Importantly, despite their widespread use in cosmetology and aesthetic dermatology, the interchangeable use of the terms "PDRN" and "PN" in the scientific literature (to describe polymers of varying lengths) has led to considerable confusion within the medical and scientific communities. To specifically address this PDRN/PN ambiguity, this narrative review proposes a standardized structure-based nomenclature for these DNA-derived polymers, the "Marques Polynucleotide Cutoff", set at 1500 kDa. Thus, we propose that the term "PDRN" should be exclusively reserved for small- and medium-chain polymers (MW < 1500 kDa), while the term "PN" should specifically be used to denote longer-chain polymers (MW ≥ 1500 kDa). In a broader perspective, this classification is based on the distinct physicochemical properties and therapeutic effects of these DNA fragments of various MWs, which are comprehensively discussed in the present review.

Keywords: DNA fragments; anti-aging; molecular weight; nomenclature; physicochemical properties; polydeoxyribonucleotides (PDRNs); polynucleotides (PNs); skin regeneration; standardization; wound healing.

Figure 1

(a) Structure of DNA and RNA molecules, highlighting the chemical group differences on the deoxyribose sugar (DNA) and the ribose sugar (RNA). (b) Flow sequence of genetic information from DNA to proteins. Firstly, DNA serves as a template to produce RNA (i.e., transcription), which is then translated into polypeptides that fold into functional proteins. DNA—deoxyribonucleic acid; RNA—ribonucleic acid.

Figure 2

Similarities and differences between cutaneous wound healing and skin anti-aging mediated by PDRN/PN action. (a) The wound healing process is constituted by four main steps (hemostasis, inflammation, proliferation, and maturation). (b) In the case of anti-aging treatments, three steps of this process are transposable with the wound healing process (inflammation, proliferation, and maturation steps). MMP—matrix metalloproteinase; PDRN—polydeoxyribonucleotide; PN—polynucleotide; ROS—reactive oxygen species.

Figure 3

In order to be converted to active forms, PN and PDRN are degraded by endogenous nucleases, producing nucleotides. The nucleotides then bind to the A_2A receptors in fibroblasts, stimulating a cascade reaction that decreases inflammation, stimulates cell migration and growth, angiogenesis, and the maturation of the ECM. In parallel, the nucleotides can be recycled through the salvage pathway, accelerating cell growth and protein production by the cells, which can include collagen, elastin, and fibronectin. ECM—extracellular matrix; IL—interleukin; PDRN—polydeoxyribonucleotide; PN—polynucleotide; TNF—tumor necrosis factor; VEGF—vascular endothelial growth factor.

Figure 4

Molecular weight ranges, potential applications, and expected clinical benefits of PDRN- and PN-based formulations and products [31]. Based on polymer size, the optimal administration route may vary. kDa—kilodalton; PDRN—polydeoxyribonucleotide; PN—polynucleotide.