Abstract
The rapid growth of nanoparticle-based therapeutics has underpinned significant developments in nanomedicine, which aim to overcome the limitations imposed by conventional therapies. Establishing the safety of new nanoparticle formulations is the first important step on the pathway to clinical translation. We have recently shown that plasma-polymerized nanoparticles (PPNs) are highly efficient nanocarriers and a viable, cost-effective alternative to conventional chemically synthesized nanoparticles. Here, we present the first comprehensive toxicity and biosafety study of PPNs using both established in vitro cell models and in vivo models. Overall, we show that PPNs were extremely well tolerated by all the cell types tested, significantly outperforming commercially available lipid-based nanoparticles (lipofectamine) used at the manufacturer’s recommended dosage. Supporting the in vitro data, the systemic toxicity of PPNs was negligible in BALB/c mice following acute and repeated tail-vein intravenous injections. PPNs were remarkably well tolerated in mice without any evidence of behavioral changes, weight loss, significant changes to the hematological profile, or signs of histological damage in tissues. PPNs were tolerated at extremely high doses without animal mortality observed at 6000 mg/kg and 48,000 mg/kg for acute and repeated-injection regimens, respectively. Our findings demonstrate the safety of PPNs in biological systems, adding to their future potential in biomedical applications.
Highlights
IntroductionThe number of nanocarriers has vastly increased in recent decades, with potential implementation across a range of biomedical fields, including targeted drug delivery [1], device-based therapy [2], medical imaging [3], regenerative medicine, and tissue engineering [4]
We assessed the cytotoxicity and biosafety of two plasma-polymerized nanoparticles (PPNs) formulations with distinct sizes, which were synthesized in acetylene-based reactive dusty plasmas (Figure 1)
Following on from our previous work, which proposed nanoparticles synthesized in carbonaceous dusty plasmas (PPN) as a versatile nanocarrier, we recently demonstrated the therapeutical potential of PPN as an effective nanocarrier for the delivery of chemotherapeutic drugs and siRNA in an established cancer model [22]
Summary
The number of nanocarriers has vastly increased in recent decades, with potential implementation across a range of biomedical fields, including targeted drug delivery [1], device-based therapy [2], medical imaging [3], regenerative medicine, and tissue engineering [4]. The unique features of nanoparticles, including their small size, high surface-tovolume ratio, and design versatility, allows for a wide selection of payloads, compositions, and targeting moieties [5,6]. These characteristics enable nanocarriers to overcome the pharmacokinetic limitations of conventional drug formulations by breaking through biological barriers and prolonging the accumulation and retention at the targeted site, thereby increasing the efficacy of the drugs [7].
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