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(A) Shown are time-lapse brightfield and fluorescence images of a HeLa cell treated with citratecapped
AuNPs and stained with FM 4-64 dye to show membranes. The inset in the top corner shows the start
position of AuNPs (red circles) and the trajectory of their movement over time (green lines). The inset below
shows a zoomed in image of particles surrounded by membrane. (B) Shown are time-lapse brightfield and
fluorescence images of a HeLa cell treated with IAuPs and stained with FM 4-64 dye. The inset in the top corner
shows the start position of IAuPs (red circles) and the trajectory of their movement over time (green lines). The
lower insets show zoomed in images of a particle in a vesicle (left), and a particle that is not membrane-bound
(right). The scale bars are 10 μm for the cells and 2 μm for the insets.

(A) Shown are time-lapse brightfield and fluorescence images of a HeLa cell treated with citratecapped AuNPs and stained with FM 4-64 dye to show membranes. The inset in the top corner shows the start position of AuNPs (red circles) and the trajectory of their movement over time (green lines). The inset below shows a zoomed in image of particles surrounded by membrane. (B) Shown are time-lapse brightfield and fluorescence images of a HeLa cell treated with IAuPs and stained with FM 4-64 dye. The inset in the top corner shows the start position of IAuPs (red circles) and the trajectory of their movement over time (green lines). The lower insets show zoomed in images of a particle in a vesicle (left), and a particle that is not membrane-bound (right). The scale bars are 10 μm for the cells and 2 μm for the insets.

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Article
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Gold nanoparticles (AuNPs) are used for a number of imaging and therapeutic applications in east and western part of the world. For thousands of years, the traditional Indian Ayurvedic approach to healing involves the use of incinerated gold ash, prepared with a variety of plant extracts and minerals depending on the region. Here, we describe the c...

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... order to obtain more information about the subcellular localization of AuNPs and IAuPs in HeLa cells, live imaging was performed using a membrane-specific dye (FM-4-64), after treatment with AuNPs or IAuPs (Fig. 5). Similar to fixed cells, AuNPs appeared to be localized to membrane-bound vesicles surrounding the nucleus as shown in Fig. 5. Tracking vesicle movement revealed trajectories that are consistent with movement along microtubule tracks, as expected for vesicles in the endomembrane system (green lines in Fig. 5). The localization of IAuPs ...
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... order to obtain more information about the subcellular localization of AuNPs and IAuPs in HeLa cells, live imaging was performed using a membrane-specific dye (FM-4-64), after treatment with AuNPs or IAuPs (Fig. 5). Similar to fixed cells, AuNPs appeared to be localized to membrane-bound vesicles surrounding the nucleus as shown in Fig. 5. Tracking vesicle movement revealed trajectories that are consistent with movement along microtubule tracks, as expected for vesicles in the endomembrane system (green lines in Fig. 5). The localization of IAuPs was similar to what had been observed in fixed cells. Some particles appeared to be surrounded by membranes, while other ...
Context 3
... after treatment with AuNPs or IAuPs (Fig. 5). Similar to fixed cells, AuNPs appeared to be localized to membrane-bound vesicles surrounding the nucleus as shown in Fig. 5. Tracking vesicle movement revealed trajectories that are consistent with movement along microtubule tracks, as expected for vesicles in the endomembrane system (green lines in Fig. 5). The localization of IAuPs was similar to what had been observed in fixed cells. Some particles appeared to be surrounded by membranes, while other particles were cytosolic, and their movement appeared to be random as shown in Fig. ...
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... with movement along microtubule tracks, as expected for vesicles in the endomembrane system (green lines in Fig. 5). The localization of IAuPs was similar to what had been observed in fixed cells. Some particles appeared to be surrounded by membranes, while other particles were cytosolic, and their movement appeared to be random as shown in Fig. ...
Context 5
... order to obtain more information about the subcellular localization of AuNPs and IAuPs in HeLa cells, live imaging was performed using a membrane-specific dye (FM-4-64), after treatment with AuNPs or IAuPs (Fig. 5). Similar to fixed cells, AuNPs appeared to be localized to membrane-bound vesicles surrounding the nucleus as shown in Fig. 5. Tracking vesicle movement revealed trajectories that are consistent with movement along microtubule tracks, as expected for vesicles in the endomembrane system (green lines in Fig. 5). The localization of IAuPs ...
Context 6
... order to obtain more information about the subcellular localization of AuNPs and IAuPs in HeLa cells, live imaging was performed using a membrane-specific dye (FM-4-64), after treatment with AuNPs or IAuPs (Fig. 5). Similar to fixed cells, AuNPs appeared to be localized to membrane-bound vesicles surrounding the nucleus as shown in Fig. 5. Tracking vesicle movement revealed trajectories that are consistent with movement along microtubule tracks, as expected for vesicles in the endomembrane system (green lines in Fig. 5). The localization of IAuPs was similar to what had been observed in fixed cells. Some particles appeared to be surrounded by membranes, while other ...
Context 7
... after treatment with AuNPs or IAuPs (Fig. 5). Similar to fixed cells, AuNPs appeared to be localized to membrane-bound vesicles surrounding the nucleus as shown in Fig. 5. Tracking vesicle movement revealed trajectories that are consistent with movement along microtubule tracks, as expected for vesicles in the endomembrane system (green lines in Fig. 5). The localization of IAuPs was similar to what had been observed in fixed cells. Some particles appeared to be surrounded by membranes, while other particles were cytosolic, and their movement appeared to be random as shown in Fig. ...
Context 8
... with movement along microtubule tracks, as expected for vesicles in the endomembrane system (green lines in Fig. 5). The localization of IAuPs was similar to what had been observed in fixed cells. Some particles appeared to be surrounded by membranes, while other particles were cytosolic, and their movement appeared to be random as shown in Fig. ...

Citations

... These variations could potentially lead to differences in the efficiency or regulation of endocytosis, thus impacting their respective abilities to uptake CDs. [43][44][45] Lastly, and unexpectedly, DT3-CDs were found to be highly enriched in the cytosol of HFF-1 and HeLa cells compared to the other CDs. These CDs were the most negative, and log P measurements revealed that they have amphiphilic properties that could permit them to passively enter cells. ...
Article
Full-text available
Carbon dots (CDs) have garnered significant interest due to their optical properties and potential applications in cell and tissue imaging. While the physicochemical properties of CDs are predicted to impact their uptake and localization in cells, few studies have directly compared CDs derived from related chemical species, yet such studies are key to revealing structure–function relationships. Herein, CDs synthesized from citric acid and five different amine passivating agents were characterized to determine how an increase in amine composition affects their physicochemical properties, uptake, and localization in HeLa (human cervical carcinoma) and HFF-1 (human foreskin fibroblast) cells. We found that all CDs have similar functional groups and fluorescence properties with monodisperse sizes ranging from 1.3 to 2.7 nm. Their surface charge increases with amine passivation, which correlated with an increase in CD uptake in both cell lines. All CDs exhibited low cytotoxicity and localized to the lysosomes in both HeLa and HFF-1 cells. However, CDs prepared using pentaethylenehexamine (PH6-CDs) were more enriched in the lysosomes compared to the other CDs, while CDs prepared using diethyltriamine (DT3-CDs) were more cytosolic. Indeed, DT3-CDs have amphiphilic properties which may permit passive entry, while hydrophilic PH6-CDs likely rely more heavily on endocytic uptake. Our findings reveal how surface chemistry directs subcellular localization, which can be used to design imaging probes that target specific cellular compartments.
... Swarna Bhasma (SB), also known as gold ash, is a metallic formulation in traditional Ayurvedic medicine that contains nano and colloidal gold particles. SB is widely known as a metabolic booster and ayurvedic physicians used to treat different diseases such as tuberculosis, cancer, bronchial asthma, rheumatoid arthritis, diabetes mellitus, anemia, nervous, and reproductive system related disorders (19)(20)(21). Ayurveda claimed that SB improves sperm count, quality and quantity of semen, and sexual activity (20,22). However, to our knowledge, there are no experimental reports available on reproductive system enhancement activity of SB in aging animals/human beings. ...
... According to Ayurveda, the ayurvedic metallic formulation is free from any toxic effects. Besides its traditional belief, various in-vitro and in-vivo toxicological studies conducted previously concluded that SB is nontoxic (19). Toxicity study of 90 days was conducted in Wistar rats where a high dose of SB (13.5 mg/kg Bwt) did not cause any alteration in weight and histopathology of organs (liver, kidney) in treated rats (24). ...
Article
Full-text available
Background: The male reproductive system undergoes several adverse age-related changes like decreased hormone synthesis, sperm count, and testicular alteration that can impact on fertility. Objective: The study aims to investigate the effects of testosterone propionate (TP), and ayurvedic formulation Swarna Bhasma (SB) on D-galactose (D-gal) induced reproductive aging in male Wistar rats. Materials and methods: 60 male Wistar rats were divided into 10 groups of 6 animals. Reproductive aging was induced by D-gal (150 mg/kg Bwt) exposure for 60 days. The rats were then treated by post and combination treatment with TP (2 mg/kg Bwt) and SB (6.75 mg/kg Bwt). Then sperm parameters, reproductive hormones, inflammatory markers, testicular antioxidant enzymes, steroidogenic enzymes, and histological manifestation of testis were evaluated. Results: Exposure of D-gal caused significant (p < 0.001) decrease in serum testosterone (T), testicular steroidogenic, and antioxidant enzymes. Administration of TP increased the serum T level, testicular antioxidant enzymes, and spermatogenic profile at a significant level of (p < 0.001) compared to D-gal. Further, the SB treatment significantly (p < 0.001) elevated the serum T level, sperm count, testicular antioxidant enzymes, steroidogenic enzymes, when compared to D-gal. Conclusion: Both the treatment of TP and SB treatments recovered the reproductive impairments caused by D-gal. However, exogenous T supplementation via TP administration is associated with various side effects during long-term use. SB is an Ayurvedic formulation having a long history of usage in India. The current findings suggest that the SB may be used as a good alternative for potentiating reproductive function in aging males.
... Studies on the cellular localization of gold and silver utilized in traditional Indian medicine, in the form of bhasmas in Ayurveda and parpams in Siddha are scarce and their mechanism of cellular entry is not known. In this regard, our group's comparative study on the chemically synthesized gold nanoparticles and the incinerated ancient Indian gold, Swarna Bhasma, proved to be compelling [18,19]. The particle sizes as well as the chemical composition of Swarna Bhasma and Veli parpam have been determined by using modern physical methods, especially, SEM with EDX, XRD, and ICP-MS (Inductively-Coupled Plasma Mass Spectroscopy) as well as DLS (Dynamic Light Scattering). ...
Article
Full-text available
Bhasmas in Ayurveda and parpams in Siddha medicine are unique herbo-metallic/mineral preparations, effective remedies, fabricated from highly purified metals, treated with a variety of herbal decoctions and incinerated at high temperatures to, finally, obtain a metal ash, having a significantly reduced size and free of toxic effects. The processing techniques of bhasmas and their use as medicines have been described in ancient texts of Ayurveda such as Rasa Shastra, Charaka Samitha and Sushruta Sambita. It has been emphasized that, while Siddha medicine is close to Ayurveda, Siddha has been closely linked to the Tantric religious movement, traced back to the 6th century AD and it is believed that Alchemy played a more central role in Siddha medicine than in Ayurveda. Some of the most important bhasmas and parpams are briefly described; their fabrication and properties are mentioned. The study of the interaction of gold bhasma and silver parpam with human cells investigated by our group is described in the second part of this work. In this section, the cellular uptake and localization of the gold and silver particles in cancerous and normal cells have been elucidated by using, principally, the hyperspectral imaging method that combines the image with the spectral information.
... Black soot and mineral powders have been used as cosmetics for millennia. Ayurvedic bhasma, one of the innovations of ancient Indian wisdom, has also been found to have nanocrystalline structure [13][14][15] . Evidently, nanoscience and nanotechnology have had applications since ancient times. ...
... This is supported by the structural study, as impure samples show more agglomeration resulting in an increase in the size of the crystallite particles. These findings accord with the requirement of multiple calcinations or the process of Marana as recommended in classical Ayurveda texts of preparation of herbal based nano-medicine, which are used by research group [13][14][15] . High temperature from continuous fire supports the conversion of different compounds into metal oxide and tiny crystals. ...
... AuNPs have distinctive physical and structural characteristics and are used in various biological applications such as interaction with living cells, and intracellular drug delivery [13][14]. Physical and structural characteristics of AuNPs, such as their size, shape, aggregation state, stability, and surface chemistry affect their interaction and the ability for cellular entry [15,16,17]. ...
Preprint
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Nano-formulations of Gold (Au) are proven drug delivery vehicles. Ayurveda i.e. Indian traditional medicine system, involves metal Bhasmas (like Au, Ag, Fe, Cu) for therapeutic purposes. Ayurveda literature prompts Gold Bhasma/Incinerated Gold Particle (InGPs) synergizes the co-administered drug and/or act as a drug delivery vehicle. Comparative physicochemical and drug encapsulation and release pattern analysis of Gold Nanoparticles (AuNPs) and InGPs was performed to test the above statement. We have loaded Rifamycin (RF) and Isoniazid (INH) over AuNPs, and InGPs, with and without nano-carrier, and checked their encapsulation and release pattern. Interestingly, Gold Bhasma has a high entrapment, and encapsulation compared to a gold nanoparticle. InGPs with a carrier(InGP + Cs) have shown increased retention capacity compared to AuNPs with a carrier(AuNP + Cs). The cumulative releasing pattern of RF/INH from AuNPs + Cs was faster than InGP + Cs suggesting the InGPs have higher drug holding capacity. InGPs with or without polymeric carriers have good entrapment and retention capacity. Obtained results demonstrate that InGPs could have more significant value and practical application in the loading and delivery of antibiotics that further indicate to address antibacterial problems effectively, especially in the case of drug resistance. With this short communication, our motto is to bring this interesting and valuable information quickly to the nano-medicine community. We elicit this appealing information that gold Bhasma could be further explored and speed up its potentiating inhibitory effects of existing antibiotics against drug-resistant bacteria and improve sustained release antibiotic delivery.
... X-ray fluorescence spectroscopy analysis of Swarna Bhasma (incinerated gold preparation) reported additional components present along with gold are likely oxygen and carbon. These components are formed by oxidation during the incineration process of gold [12]. The energydispersive x-ray spectroscopy (EDX) analysis of Swarna Bhasma revealed the presence of 97.40% gold and other elements present in trace amounts like Na, Fe, Al, K, Ag Ca, and C [13]. ...
... Physical properties of Swarna Bhasma and gold nanoparticles are different. Swarna Bhasma enters in the cells via macropinocytosis or clathrin-independent endocytosis, whereas gold nanoparticles enter into the cells via clathrin-dependent endocytosis [12]. Rajata Bhasma reported to have better antimicrobial effect than silver nanoparticles against Bacillus subtilis and Klebsiella pneumonia [64]. ...
Article
Ayurvedic nano-medicine preparations (ANMPs), Bhasma and Sindura, are considered as most effective dosage forms in Ayurveda. These are the preparations of metals and minerals used for therapeutic purposes in Ayurveda. Those are prepared by repeated trituration with liquid media from plant materials and incineration at high temperature above 650°C. These preparations are claimed as biologically produced nano-medicines formed by metallic/mineral nanoparticles. Presence of carbonaceous nano-materials is also reported in these preparations, in the form of fullerene and others. The complexes of metallic/mineral nanoparticles with carbonaceous nano-materials are formed by the processes of physisorption and chemisorption. The carbonaceous nano-materials are reported to have different biological effects. The ANMPs are safe and are having various biological activities, i.e., antioxidant, immunomodulatory, anti-inflammatory, antitumor, antibacterial, and others. These biological activities of ANMPs are due to the presence of nano-metal or mineral particles conjugated with carbonaceous nano-materials. The conjugation of metals and minerals nanoparticles with nano-carbons makes these preparations biologically safe and therapeutically more effective. Probable effects of the carbonaceous nano-materials present in the ANMPs are discussed in this review.
... Larger solid particles enter cells more efficiently via phagocytosis. For instance, it is reported that larger gold NPs can be localized in the nucleus of HeLa cells during cell division (Beaudet et al., 2017). Smaller particles (< 100 nm) adhere to Clathrin and Caveolae proteins and form endocytosis, helping cells phagocytize particles (Kashani et al., 2018). ...
Article
Full-text available
Anti-inflammatory, antiviral, and anti-cancer treatments are potential applications of nanomaterials in biology. To explore the latest discoveries in nanotechnology, we reviewed the published literature, focusing on co-assembled nanoparticles for anti-inflammatory and anti-tumor properties, and their applications in animal husbandry. The results show that nanoparticles have significant anti-inflammation and anti-tumor effects, demonstrating broad application prospects in animal breeding. Furthermore, pooled evidence suggests that the mechanism is to have a positive impact on inflammation and tumors through the specific drug loading by indirectly or directly targeting the disease sites. Because the precise regulatory mechanism remains unclear, most studies have focused on regulating particular sites or even specific genes in the nucleus by targeting functional co-assembled nanoparticles. Hence, despite the intriguing scenarios for nanotechnology in farmed animals, most results cannot yet be translated into field applications. Overall, nanomaterials outperformed similar materials in terms of anti-inflammatory and anti-tumor. Nanotechnology also has promising applications in animal husbandry and veterinary care, and its application and development in animal husbandry remain an exciting area of research.
... Bioavailability is the first aspect in pharmacokinetics. Considering the therapeutic potential of gold bhasma [2,3], preliminary exploration of its bioavailability was carried out. There are various approaches for such studies [4 Remington's The science and practice of pharmacy, 21 st edition, pp 1038]. ...
... It is reported that Ayurvedic swarnabhasma [gold bhasma] is comprised of nano-particles of gold [2,3]. It is delivered by oral route directly or sublingually by some physicians. ...
... Ayurvedic text Rasaprakashsudhakar has reported a guideline of consumption of gold bhasma for upto 20 years [24] in 60 mg daily dose for longevity. Long term consumption may lead to cellular entry of gold bhasma particles in cells [3], which needs exploration. Hence steady state concentration study would be essential in case of gold bhasma. ...
Article
Full-text available
Background: Gold bhasma [Swarnabhasma] is a ancient Ayurvedic medicine used for rejuvenation and longevity. This is a preliminary attempt to study the bioavailability of this medicine. Objectives: It was aimed to estimate comparative bioavailability of gold bhasma up to five hours after oral dose with four different anupana. Materials and methods: In this in vivo study, 30 healthy human participants were allocated randomly into five groups having six individuals each. Gold bhasma in 30 mg dose was administered orally with four different anupana viz honey [2.5 gm], black pepper-ghee combination [250 mg and 2.5 gm respectively], lactose [250 mg], glucose [250 mg], and plain to participants in each group. Blood samples were collected at 0, 1, 3 and 5 hours after dose. Gold levels in blood were assessed by inductively coupled plasma mass spectrometry [ICP-MS]. Results: Gold levels in all blood samples were in traces. Average Cmax was 0.002333 microgram of gold per liter and Tmax was at 3 hours for honey anupana, showing maximum Cmax among all groups. Conclusions: Preliminary results indicate that bioavailability of gold from gold bhasma may be less than 0.01 % upto first five hours. Gold bhasma mixed with honey resulted in attainment of maximum Cmax. It is evident that accompanying media [anupana] play an important role in absorption of gold bhasma.
... This process might take thirty minutes to several hours with respect to cell type and NPs properties. Larger particles could even enter the nucleus; for example, larger gold NPs have been found to be able to localize in the nucleus of HeLa cells during cell division [48,49]. Particles in the size range of 200-1500 nm in diameter can be taken up by phagocytosis [17]. ...
Article
Full-text available
With the advancement of nanotechnology, the nano-bio-interaction field has emerged. It is essential to enhance our understanding of nano-bio-interaction in different aspects to design nanomedicines and improve their efficacy for therapeutic and diagnostic applications. Many researchers have extensively studied the toxicological responses of cancer cells to nano-bio-interaction, while their mechanobiological responses have been less investigated. The mechanobiological properties of cells such as elasticity and adhesion play vital roles in cellular functions and cancer progression. Many studies have noticed the impacts of cellular uptake on the structural organization of cells and, in return, the mechanobiology of human cells. Mecha-nobiological changes induced by the interactions of nanomaterials and cells could alter cellular functions and influence cancer progression. Hence, in addition to biological responses, the pos-sible mechanobiological responses of treated cells should be monitored as a standard methodology to evaluate the efficiency of nanomedicines. Studying the cancer-nano-interaction in the context of cell mechanics takes our knowledge one step closer to designing safe and intelligent nanomedicines. In this review, we briefly discuss how the characteristic properties of nanoparticles influence cellular uptake. Then, we provide insight into the mechanobiological responses that may occur during the nano-bio-interactions, and finally, the important measurement techniques for the mechanobiological characterizations of cells are summarized and compared. Understanding the unknown mechanobiological responses to nano-bio-interaction will help with developing the application of nanoparticles to modulate cell mechanics for controlling cancer progression.
... 44 SEM and X-ray diffraction analysis showed that Swarna Bhasma are large aggregates of smaller nanoparticles of about 60 nm in size. 45 Immunomodulation, nontoxicity and the ability to target drugs to the site of action are characteristics of a properly prepared Bhasma. 19 Medicinal plants used in the various stages of Bhasma preparation are believed to reduce the toxicity of metals (Table 1). ...
Article
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Rajendran K Selvakesavan, Gregory Franklin Institute of Plant Genetics of the Polish Academy of Sciences, Poznan, PolandCorrespondence: Gregory FranklinInstitute of Plant Genetics of the Polish Academy of Sciences, 34 Strzeszynska street, Poznan, 60-479, PolandTel +48 61 655 0266Email fgre@igr.poznan.plAbstract: The use of medicinal plants in green synthesis of metal nanoparticles is increasing day by day. A simple search for the keywords “green synthesis” and “nanoparticles” yields more than 33,000 articles in Scopus. As of August 10, 2021, more than 4000 articles have been published in 2021 alone. Besides demonstrating the ease and environmental-friendly route of synthesizing nanomaterials, many studies report the superior pharmacological properties of green synthesized nanoparticles compared to those synthesized by other methods. This is probably due to the fact that bioactive molecules are entrapped on the surface of these nanoparticles. On the other hand, recent studies have confirmed the nano-dimension and biocompatibility of metal ash (Bhasma) preparations, which are commonly macerated with biological products and administered for the treatment of various diseases in Indian medicine since ancient times. This perspective article argues for the prospective medical application of green nanoparticles in the light of Bhasma.Keywords: green synthesis, nanoparticle, Bhasma, medicinal plants, phytonanomedicine