Gold Nanoparticles

The combined activity of anticancer drugs (bleomycin and doxorubicin) and drug carriers (gold NPs) on HeLa cancer cell lines is analyzed. This combination decreases drug resistance and improves the outcomes of chemotherapy. It also improves the therapeutic efficacy and reduces the drug concentration. This drug carrier has excellent stability, high drug loading, an excellent drug release behavior, and half maximal effective concentration (high EC 50) values. Figure 13.11 shows the synthesis and characterizations of anticancer drugs loaded with gold nanoparticles (AuNPs) [55].

AuNPs are promising for miRNA delivery by decorating the NPs with polyethyleneimide and liposomes. These polymers with ultra-small gold NPs can offer high transfection efficiency, more cellular uptake and less toxicity [56]. AuNPs have been synthesized for curcumin drug delivery. In this process, initially, gold precursor has been chemically reduced to prepare AuNPs. In the next step, gelatin (biopolymer) has been coated on the prepared AuNPs. Finally, the resulted nanocomposite (curcumin drug carrier) has been loaded with curcumin (for curcumin delivery applications) [57]. It is observed that the gelatin coating on AuNPs is the major issue in the drug delivery system.

Graph shows the comparison of in vitro dissolution of marketed KCl syrup formulation and Eudragit E100

FIGURE 13.10 Graph shows the comparison of in vitro dissolution of marketed KCl syrup formulation and Eudragit E100 (a water-insoluble polymer) coated KCl syrup formulation. Eudragit E100 is coated on KCl to mask the unpleasant taste effectively (2 folds) that improves the palatability of KCl. It releases the KCl completely (100%) in 30 minutes but the conventional KCl syrup releases in 15 minutes. (From Kulkarni Madhur et al. 2019.)

Synthesis of gold nanoparticles (AuNPs) loaded with anticancer drugs bleomycin (BLM) and doxorubicin (DOX). (a) Synthesis and conjugation steps

FIGURE 13.11 Synthesis of gold nanoparticles (AuNPs) loaded with anticancer drugs bleomycin (BLM) and doxorubicin (DOX). (a) Synthesis and conjugation steps: PEG-capped AuNPs (SI); PEG-AuNPs linked to DOX (S2); PEG-AuNPs linked to BLM (S3); PEG-AuNPs linked to both DOX and BLM (S4). (b) Formation of S2, S3 and S4 NPs. (c) XRD spectrum of SI (d) FTIR spectra of SI and S3. (From Farooq Muhammad et al. 2018.)

The size of the AuNPs plays a key role in the release of curcumin. Figure 13.12 exhibits the loading of curcumin on gelatin-gold nanocomposite.

Iron Oxide Nanoparticles

Iron oxide NPs have attractive magnetic and biological properties. Higher-level drug loading is possible with them. [58]. According to the literature, iron oxide NPs can be utilized as nanodrugs safely. There is no histopathological damage or any other damage to the organs while administering the iron oxide NPs. Also, the cytotoxic effect is at a very much lower level.

Smart NPs release the drugs depending on the pH level. Mohanta et al. designed the pH-responsive smart NPs using iron oxide NPs with PEGylation. These smart NPs will deliver the drug as and

Schematic diagram shows the steps involved in the curcumin loading on the gelatin-coated gold nanoparticles

FIGURE 13.12 Schematic diagram shows the steps involved in the curcumin loading on the gelatin-coated gold nanoparticles.

when needed. To prepare the smart drug, initially spherical iron oxide NPs with a size of 8-20 nm are synthesized by precipitation method. After that, the synthesized NPs are coated w'ith PEG-400. Finally, the PEG-coated iron oxide NPs are loaded with anticancer drug daunorubicin. Optimization of the PEG/iron oxide NPs ratio can enhance the drug loading. A high amount of drug release at low level pH confirms the smart nature of the NPs [59].

Rat studies are performed for the targeted delivery of PEGylated iron oxide NPs for lung cancer (H460). Targeting can be achieved by decorating the NP with the anti-epidermal growth factor receptor monoclonal antibodies [60]. The quantity of iron oxide NPs accumulated at the tumor site in rats can be analyzed in MRI by the magnetic targeting method. A magnetic field of 0.4 Tesla is applied for 30 minutes and the NPs of 12 mg/kg are injected intravenously. Applying the magnetic targeting for four hours increases the NP exposure to glioma up to five-fold [33].

Flavonoids from natural materials have low bioavailability. Flavonoid quercetin is loaded inside iron oxide NPs in order to enhance its bioavailability property. Using computational methods, quercetin flavonoid is targeted towards proteins involved in the learning and memory functions of rats. Better learning and memory functions are identified in quercetin loaded iron oxide NPs. Figure 13.13 shows the characterization studies of the quercetin loaded superparamagnetic iron oxide nanoparticles using different tools [61].

Biodistribution and toxicity studies are more important for clinical translation of newly designed drugs. Polyethyleneimine (PEI) coated iron oxide NPs are used for low interference RNA delivery. This NP drug conjugate is administered via intravenous injection. Accumulation studies are performed by Prussian blue straining in the heart, liver, spleen, lung, and kidney. The results show' that the cytotoxic effect is very low. The NP drug is deposited in large amounts in the liver and spleen. However, there is no evidence for any histopathological damage or any other damage to the organs. It is concluded that PEI-coated iron oxide NPs are the best in vivo carrier for siRNA [62].

Iron oxide NPs are utilized in biomedical applications. The polymer coated on the NPs, and size of the NPs, decides the uptake of the drug. PEG-coated iron oxide NPs exhibit less uptake in cells when compared to polyethyleneimine coated iron oxide NPs. PEG-coated iron oxide NPs induce

Characterization of quercetin conjugated with superparamagnetic iron oxide nanoparticles

FIGURE 13.13 Characterization of quercetin conjugated with superparamagnetic iron oxide nanoparticles (QT-SPION). (A) FT-IR spectra (a) dextran-coated, (b) pure QT. (c) QT- SPIONs. (B) XRD pattern (a) QT, (b) dextran-coated SPIONs (c) QT- SPIONs. (C and D) SEM and EDX analyses of QT- SPIONs respectively. (E and F) Dynamic light-scattering spectra of dextran-coated SPIONs and QT-SPIONs. (From Amanzadeh Elnaz et al. 2019.)

autophagy in cells which prevents cytotoxicity of iron oxide NPs. In the case of comparing two different sizes of PEG-coated iron oxide NPs, tumors take up more NPs of 10 nm size than of 30 nm. No toxicity is observed with PEG-coated iron oxide NPs. However, some dose-dependent lethal toxicity is observed with PEI-coated iron oxide NPs. Figure 13.14 shows the ТЕМ and DLS images of polymer-coated iron oxide NPs. It also shows the distribution curves related to the distribution of iron oxide NPs in tumors and in the internal organs obtained from the ICP-MS analysis [63].

Quantum Dots

Quantum dots are used for both diagnosis and therapeutic applications of cancer cells. Nowadays graphene quantum dots are used for the treatment of breast cancer cells using herceptin (antibody) and cyclodextrin (polymer) as labels. Doxorubicin is loaded as the cancer drug inside the drug

ТЕМ images and dynamic light scanning

FIGURE 13.14 ТЕМ images and dynamic light scanning (DLS) size distribution graphs of SEI-10, SMG- 10, and SMG-30. ТЕМ images of SEI-10. SMG-10, and SMG-30 are shown in (A). (B) and (C) respectively. The related DLS size distributions are shown in (D), (E) and (F). In vivo bio-distribution of different IONPs (1.5 mg Fe/kg) in SKOV-3 tumor of mice is shown as graphs (G) and (H). The distribution of IONPs (G) in tumors (H) in the internal organs. The distribution has been analyzed by ICP-MS after 24 hours of the intravenous injection administration of IONPs. Magnetic iron oxide nanoparticles (IONPs); SKOV-3 ovarian cancer cells; 10 nm size IONPs with PEI coating (SEI-10); 10 nm and 30 nm size IONPs with PEG coating (SMG-10 and SMG-30). (From Feng Qiyi et al. 2018.)

carrier graphene quantum dots. Cancer cells are more acidic in nature. This allows the quantum dots drug carrier system to control the release of the drug. Cell viability studies and confocal laser scanning microscopy analysis show' that this system can offer potential anticancer activity against breast cancer cells [64].

Carboxylated graphene quantum dots are analyzed in vivo for their biodistribution and toxicity studies. Graphene quantum dots are highly water-soluble in nature. They were administered through intravenous injection to mice. It was found that graphene quantum dots accumulated in the liver, spleen, lung, kidney, and tumor sites. They were administered at 5 mg/kg or 10 mg/kg dosage level for 21 days. The results showed that there was no toxicity, and no organ damage was found in mice [65].

Cytotoxicity is much lower in graphene quantum dots because of the high oxygen content. Graphene quantum dots are not accumulated in the main organs, and clearance through the kidneys is fast. There is no in vivo and in vitro toxicity while using graphene quantum dots [66]. It is observed from the literature that graphene quantum dots can be used in cancer treatment with a high degree of safety because they have no side effects or have very few side effects.

It is observed that cancer cells are more acidic in nature. However, acidity or alkalinity of foods does not alter the cancer risk. The American Institute for Cancer Research argues that acidity or alkalinity of foods neither decreases nor increases the pH level in the human body. Modifications in the cell surroundings in the body, i.e. making them less-acidic or alkaline (high pH) and less cancer- friendly, are virtually impossible. Slight changes in the body’s pH level lead to a threat to life [67].

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