Multifarious Applications of PtNPs

The unique features of PtNPs, such as surface functionalities; size; size distribution; shape; porosity; surface area; composition; crystalline nature; agglomeration; and electro, catalytic, thermal, and plasmonic properties, make their application desirable in various fields (Figure 14). Recently, PtNPs have garnered a steadily growing interest for different biomedical applications such as antimicrobial agents, anticancer agents, targeted drug delivery, hyperthermia, photoablation therapy, bioimaging, and biosensing. Bimetallic NPs such as iron platinum (Fe–Pt) NPs possess unique chemical and magnetic properties such as chemical stability, superparamagnetization, high Curie temperature, high saturation magnetization, and high X-ray absorption. These unique properties provide the potential of their application in hyperthermia treatment, as MRI contrast agents, in drug delivery, and as biosensors [142–159].

Figure 14. Physicochemical properties of platinum nanoparticles.

Antibacterial Activity of Platinum Nanoparticle

The current scenario shows paramount importance of PtNPs in human health and for the protection from various diseases caused by microorganisms. However, microorganisms are powerful and attain resistance to various antibiotics. Because of the recent increase in bacterial resistance, alternative therapeutic agents that are nontoxic to human beings but toxic to pathogenic microorganisms are urgently required. Therefore, the development of NP mediated antimicrobial agents is most warranted. Recently, several studies have focused on NP-based therapeutic agents against pathogenic bacteria. Metallic NPs such as, Pt, Ag, Pd, Cu, Au, ZnO, and TiO₂ play a vital role in antibacterial activity against pathogens [160]. The antibacterial activity depends on NP morphology, size, and shape and also its surface charges. Most metallic NPs like Ag, Pt, Au, Pd, ZnO, and Cu have a negative zeta potential and thus have potential cell damaging properties. Although PtNPs have a more negative zeta potential and cause severe damage to the cells, they show enhanced antibacterial activity [161]. Apigenin functionalized PtNPs exhibited significant antibacterial activity against Pseudomonas aeruginosa and Staphylococcus aureus (Figure 15).

Figure 15. Antibacterial activity of PtNPs against Gram negative and Gram-positive bacteria. Effect of apigenin mediated synthesis of PtNPs on cell survival of P. aeruginosa and S. aureus was analyzed. All the test strains were incubated in the presence of different concentrations of PtNPs (25–150 µg/mL). Bacterial survival was determined at 24 h by a colony forming unit (CFU) assay. The results are expressed as the means ± SD of three separate experiments, each of which contained three replicates.

Previously, Rosenberg et al. [162] demonstrated that platinum electrolysis products inhibit growth of Gram-negative bacterium Escherichia coli and the multiplication of cell. Four years later, they again demonstrated that the square planar form of platinum was highly effective against rat sarcomas. Ma et al. [163] reported that a combination of quaternary ammonium-based antibacterial monomers with colloidal PtNPs potentially inhibits Streptococcus mutans. Polyaniline/Ag-Pt nanocomposite inhibits growth of Staphylococcus aureus [164]. Palladium complexes of polyamide S-containing sulfones showed the highest antibacterial activity against Staphylococcus aureus and E. coli and antifungal activity against Aspergillums flavus and Candida albicans [165]. Bimetallic NPs (AuPt) with sizes ranging between 2 and 3 nm have potent antibacterial activity against human pathogenic organisms such as E. coli, Pseudomonas aeruginosa, Klebsiella pneumonia, and Salmonella choleraesuis [166]. These reports suggested that bacterial growth inhibition is correlated with ATP production and mitochondrial membrane potential. Another recent report described that five different shapes and sizes of polyvinylpyrrolidone-coated PtNPs ranging between 2 and 20 nm were used to examine the antibactericidal activity against P. aeruginosa. They observed that NPs less than 3 nm in size were toxic to P. aeruginosa even at low concentrations, whereas NPs >3 nm in size showed no toxicity but only interacted with the bacterial membrane [167]. Two different sizes of PtNPs with PVP coating ranging between 5.8 and 57 nm were used to evaluate the antibacterial activity against E. coli and S. aureus. It was observed that the smaller NPs inhibited the proliferation of gram negative bacteria E. coli. These results agreed with those of a previous report [168]. Subsequently, Ahmed et al. [169] (2016) reported the antibacterial activity of PtNPs 2–5 nm in size against gram positive and gram negative bacteria. As a result, the PtNPs reduced bacterial cell viability through reactive oxygen species (ROS) production, led to membrane integrity loss, and also increased the survival rate of infected Zebra fish. Polyaniline/Pt-Pd nanocomposite shows potential antibacterial activity against Streptococcus and Staphylococcus species, E. coli, and Klebsiella spp. [170]. Platinum–PMMA nanocomposites (PtNCs) inhibit the cell viability of Streptococcus mutans and Streptococcus sobrinus [171]. Pt/Ag bimetallic NPs (BNPs) decorated on porous reduced graphene oxide (rGO) nanosheets exhibited increased antibacterial activity against E. coli on interfaces between metal compositions, rGO matrix, and bacteria. The release of nanocomposites led to a rapid release of silver ions, thus trapping the bacteria in the porous rGO matrix. Polyvinylpyrrolidone (PVP) as PVP/PtNP nanocomposites shows potential antibacterial activity against E. coli, Lactococcus lactis, and Klebsiella pneumoniae [172]. Biologically synthesized PtNPs using rind extract of the fruit of Garcinia mangostana showed antibacterial activity against Staphylococcus spp., Klebsiella spp., and Pseudomonas spp. (except Bacillus spp.). The highest activity was observed against Klebsiella spp. compared with other bacterial species.

Antifungal Activity of Platinum Nanoparticles

Commercial antifungal agents lead to side effects such as liver damage, nausea, renal failure, increase of body temperature, and diarrhea. At present, alternative therapy is required for recovery from fungal disease. Previously, Gardea-Torresdey et al. [81] reported silver NPs as having potential antifungal activity against spore-producing fungi. Recently, a study compared the antifungal activity of PtNPs and commercially available antifungal agents. The biofabricated PtNPs showed potential antifungal activity against different pathogenic fungi such as C. acutatum, C. fulvum, P. drechsleri, D. bryoniae, and P. capsici [94]. The persistence of the biopolymer mediated synthesized platinum nanocomposites (GKPtNPs) was assessed to analyze the antifungal activity against fungal strains such as A. parasiticus and A. flavus. They observed antifungal activity of the nanocomposite induced the morphology of the mycelia, membrane damage, increased the level of ROS, eventually leading to DNA damage and cellular death [173].

In Vivo Toxicity of PtNPs

Asha Rani et al. synthesized different type of nanoparticles with various sizes (silver 3–10 nm, platinum 5–35 nm, and gold NPs 15–35 nm) using polyvinyl alcohol as capping agent and investigated the impact synthesized NPs. Polyvinyl alcohol capped silver NPs exhibited significant toxicity in Zebrafish embryos followed by PtNPs. No significant toxicity was observed with gold NPs. Silver and PtNPs revealed that AgNPs and PtNPs showed size-dependent toxicity in aquatic zebrafish embryos [221]. Recently, Claudia et al. [222] reported that citrate coated PtNPs increased the toxicity of mammalian liver cell line HepG2 at higher concentrations of PtNPs, whereas lower concentrations of PtNPs induced multiple stress response factors. PtNPs a caused size and dose-dependent effect on DNA strand breaks in human colon carcinoma cells (HT29) and increased the content of platinum in DNA [181,223]. Mice treated with PtNPs showed proinflammatory responses, and PtNPs increased various proinflammatory cytokines, such as IL-1, TNF-alpha, IL-6, IL-2, IL-12, IL-4, and IL-5, and concomitantly decreased intracellular levels of GSH [33]. Keratinocytes and mammary breast cells were incubated with folic acid functionalized PtNPs with an average size of 2–3 nm and showed significant toxicity toward cancer rather than non-cancer cells, suggesting that these PtNPs specially target cancer cells [224]. A comparative toxicity study between two different type of PtNPs such as sub-nanosized platinum particles (snPt) and nano-sized PtNPs was performed in the mouse liver. After intravenous administration of snPt into mice, the mice showed acute hepatic injury and increased levels of serum markers of liver injury and inflammatory cytokines. In contrast, administration of nano-sized platinum particles did not produce these abnormalities. Therefore, snPts have the potential to induce hepatotoxicity [225]. Further, authors demonstrated that single intravenous doses of snPt1 in in mice induce necrosis of tubular epithelial cells and urinary casts in the kidney, without causing any effect on lung, spleen, and heart, and cause a dose-dependent elevation of blood urea nitrogen, which is an indicator of kidney damage, whereas snPt induced significant cytotoxicity [225].

Conclusions and Future Perspectives

Platinum plays a crucial role in industrial applications such as a catalyst in fuel cells and in biosensors. Recently, Pt-based nanomaterials have attracted interest in both academic and industrial fields because of their unique features and function as nanocarriers, nanozymes, and nanosensors for diagnostic purposes. In this review, we discussed various methods for the synthesis of PtNPs including physical, chemical, and biological methods and provided a detailed account of biological methods. For the past decade, considerable progress has been made in the synthesis of monodispersed and well-defined structures of PtNPs with sizes ranging from 1.2 to several nm. Furthermore, we discussed the working principles and application of analytical techniques used for characterization of NPs. More importantly, we discussed the toxicological effect, biomedical applications, and use of PtNPs in combination therapy. For a long time, Pt-based materials have played a critical role in clinical research to overcome the undesired side effects of chemo- and radiation therapy. Thus, the diagnostic and medical industries are exploring the possibility of using PtNPs as a next-generation anticancer therapeutic agent. Although, biologically prepared nanomaterials exhibit high efficacy with low concentrations, several factors still need to be considered for clinical use of PtNPs such as the source of raw materials, the method of production, stability, solubility, biodistribution, controlled release, accumulation, cell-specific targeting, and toxicological issues to human beings. The development of PtNPs as an anticancer agent is one of the most valuable and warranted approaches for cancer treatment. The future of PtNPs in biomedical applications holds great promise, especially in the area of disease diagnosis, early detection, cellular and deep tissue imaging, drug/gene delivery, as well as multifunctional therapeutics. Furthermore, to overcome the obstacles in exclusive multidrug resistance, multifunctional PtNPs need to be designed for diagnosis and targeting and as nanocarrier and phototherapeutic agents. The current emphasis of molecular medicine is to develop more novel tools, which can be used for early-stage disease diagnosis and long-term availability in the cellular system. Integration of nanomaterials, especially PtNPs, could extend the construction of the theragnostic platform, which combines therapeutics with diagnostics, to make the diagnosis processes more simple and rapid and less invasive. Furthermore, progressive development of novel nanocomposites containing PtNPs with multifunctional modalities could lead to better ways to use PtNPs as nano-theragnostic entities in biomedicine.

As the usage of PtNPs shows immense potential in the medical field, various new modalities need to be developed. Although various methods are available to prove the efficacy of nanomaterials, the synergistic effects of PtNPs and low concentration of anticancer drugs on anticancer activity/tumor reduction are still obscure. Therefore, more studies are required to explain the synergistic effect of PtNPs with anticancer drugs at a single time point. These studies could provide an understanding of the mechanisms and efficiency of the synergistic effect of two different agents or multiple agents; thus, they would help to develop a novel system bearing multiple components with synergistic effects for the treatment of various types of cancer. Although PtNPs have been focused on for therapeutic purposes, further research is required in animal models along with multicenter studies to confirm the mechanisms and to gain a comprehensive picture of biocompatibility vs. toxicity of PtNPs. Finally, if we succeed in all these studies, it would help the researchers of the nanoscience and nanotechnology community to develop safer, biocompatible, efficient cancer or antiangiogenic agents containing PtNPs. In future, multifunctional PtNPs would be an attractive platform for biomedical applications and may change the business model of pharmaceutical industries.

The publication can be found here: https://www.mdpi.com/2079-4991/9/12/1719/htm