Nanotechnology's latest oncolytic agent: silver, cancer, & infection associations

Townsend Letter for Doctors and Patients,  May, 2006  by John Apsley,  Kent Holtorf,  Eric Gordon,  Wayne Anderson,  Rashid Buttar

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Introduction

Silver-based drugs have one core common denominator--their active ingredient is their content of "oligodynamic" silver ions (i.e., [Ag.sup.+]). Carl Nageli (1893) first coined the term oligodynamic (from the Greek oligos = few and dynamis = power). Nageli discovered that exceedingly small metal ion concentrations demonstrate extraordinary antimicrobial properties. (1) In 2003, Rentz provided a comprehensive, retrospective review on the universal antimicrobial effects of oligodynamic [Ag.sup.+]. From the historical authoritative medical literature, he documented hundreds of viral, bacterial/spirochete, fungal, and protozoan pathogens that succumb to silver-based drugs containing sufficient amounts of oligodynamic [Ag.sup.+]. (2)

Modern nanoscience is still making new discoveries regarding oligodynamic metals. Nanoscientists appear positioned to develop some of the most complicated strategies for fighting cancer. For example, they are discovering that cancer drugs must be able to easily disrupt and penetrate tumor cell membranes in situ to enable the fullest possible oncolytic effects. Picoscalar or near-picoscalar oligodynamic [Ag.sup.+] hydrosol enjoys the greatest surface presentation (i.e., ~6 [km.sup.2] per gram Ag) (3,4) for tumor cell membrane adherence and penetration, leading to greater oncolytic effects.

History

The works of Moyasar et al. (1990), (5) Hamilton-Miller and Shah (1993), (6) Zhao and Stevens (1998), (7) Baker et al. (2004), (8) Sondi and Salopek-Sondi (2004), (9) and Morones et al. (2005) (10) collectively established that the therapeusis of bioactive silver extends well beyond its virotoxicity. It is also a broad-spectrum bactericidal and fungicidal agent. Berger showed that oligodynamic [Ag.sup.+] is ten to 100 times superior to silver sulfadiazine for both gram-positive and gram-negative pathogens in terms of achieving the minimal lethal dose (MLD). (11)

It has long been suspected that infectious agents are associated with solid tumor cancers (a notable example is Kaposi's Sarcoma) as well as non-tumor-based cancers such as leukemia. Also, cancer patients often undergo immune suppression therapy, allowing for multiple pathogen foci to seed. Oligodynamic [Ag.sup.+] may have the potential to play a dual role: either destroy the infectious etiological agent of the cancer and/or destroy the pathogen loads arising within immunocompromised patients.

Impact

In the US, cancer is the second leading cause of death in humans. (12) Virginia Livingston-Wheeler was among the first to propose an infectious etiology for cancer. (13) Cancer rates stemming from an infectious etiology (e.g., HIV, (14,15) HHV8, (16) HPV16, (17) and EBV (18)), as well as infectious rates from immunocompromised patients (e.g., BK and JC Polyomaviruses, (19,20) Respiratory Syncytial virus, Influenza viruses, and Parainfluenza viruses, (21) Fungemia, (22,23) Rotavirus, (24) CMV, (25) and Streptococcus pneumoniae (26)) have climbed alarmingly over the past two decades. Rentz documented that many of these cancer-associated infections are susceptible to oligodynamic [Ag.sup.+]. (2)

Discussion

One critical strategic advantage to ~1 nm to 10 nm or less (e.g., picoscalar) silver particles is their ability to absorb, (27,28) interact with, and destroy bacteria; (10) affect abnormal human tissue in situ; (33) or favorably upregulate immune tissues and healing mechanisms. (3) These abilities are augmented by the fact that [Ag.sup.+] hydrosols comprised of the lowest-sized nanoclusters and even picoclusters enjoy the greatest surface presentation and Particle Diffusion Coefficient ([10.sup.-5][cm.sup.2]/sec) for bioactivity ever created. (3,37) At this size range, in vitro studies sponsored by NASA at the University of Wisconsin offer a fascinating mathematical probability: by skillfully administering [Ag.sup.+] hydrosol in vivo to saturate target loci or foci, picoscalar [Ag.sup.+] will impregnate all collective atoms within each tumor cell or pathogen cell with up to one silver ion. (29) This saturation potential supercharges [Ag.sup.+]'s ability to displace the [K.sup.+]-dependent, glucose transport mechanism (the exclusive means by which cancerous cells feed themselves, as opposed to normal cells that enjoy two other additional means to feed themselves), thereby selectively starving cancer cells without harming normal cells.

Landmark studies over the past several decades have demonstrated that oligodynamic [Ag.sup.+] could play a pivotal role in overcoming cancerous processes. This article will review these findings and offer a proposal for future studies and protocol development.

In Vitro Testing

Becker reported in 1985 that his research group had "... studied malignant fibrosarcoma cells (cancerous fibroblasts) and found that electrically injected silver suspended their runaway mitosis." (30,31) In 2003, a similar in vitro test was conducted utilizing 1.44 ppm, 2.88 ppm, 5.75 ppm, 10 ppm, 11 ppm, 11.5 ppm, and ~22.5 ppm concentrations of picoscalar or near-picoscalar oligodynamic [Ag.sup.+] hydrosol against immortal (cancerous) L-929 Murine fibroblast cell lines (ATCC CCL 1, NCTC Clone 929, of strain L, or equivalent source). Respectively, the oncolytic effects upon the cancerous fibroblasts ranged from 55% to 84% and were [Ag.sup.+] concentration-dependent. (32)