Nanomedicine Journal
Volume:8 Issue: 4, Autumn 2021

Application of nanoparticles have in the core of researchers attention for both imaging and therapy of cancers. This review article aimed to prepare an outline on recent applications of iodine nanoparticles (INPs) as theranostic agents in both diagnosis and therapies. Among various strategies are used in treatment of cancers, radiotherapy with radiopharmaceutical agents especially radioisotope of iodine displays satisfactory results for numerous types of cancers. In recent years, new investigations were done in order to develop the novel structure of INPs. These nanoprobes could act as efficient theranostic purposes. Iodine nanoparticles may be applied in nuclear medicine imaging and may be effective with mega voltage (MV) photons in cancer therapy, but this remains to be tested with different cancer cells. By using INPs, effective steps can be taken in the future in both diagnosis and treatment of cancers. This review emphasized the recent research findings on the application of INPs in medical imaging and therapeutic of cancers. The current challenges and the perspectives for their future applications were also represented and discussed.

Terbinafine (TBF) is a drug with well-known antifungal properties effective against skin dermatophyte infections and nail particularly in treatment of pityriasis (tinea) vesicolor due to Malassezia furfur. Terbinafine topical administration is often recommended because commercial conventional terbinafine hydrochloride tablets are more expensive and have potential for significant adverse effects. Only less than 5% of terbinafine is absorbed in conventional topical forms. Novel nano-formulation approaches would be an efficient way to enhance penetration and abortion of topical drugs and eliminate limitations of conventional drug delivery systems. As conclusion, we believe that administering the Terbinafine in nano-formulations, according to different studies, could increases penetration of TBF through stratum corneum and viable epidermis and light the path of nano-structural delivery system in clinical application. Present overview aims to evaluate nano-strategies applied to improve permeation profile and terbinafine skin delivery.

Diabetes is related with the higher blood levels of liver enzymes and inflammatory factors.  Galega officinalis is used as a medicinal plant for treatment of diabetes traditionally. In this work, silver nanoparticles (Ag-NPs) were synthesized with green method using Galega officinalis extract. The synthesized green Ag-NPs were characterized completely. Intact or diabetic rats receieved intraperitoneal injection of saline or 2/5mg/Kg  green synthesized Ag-NPs. Mean serum levels of glucose,  hepatic enzymes and hematological parameter were determined. Gene expression of tumor necrotic factor alpha (TNF-α) was done by real-time PCR.   Synthesis of green synthesized Ag-NPs was confirmed by FT-IR, XRD and UV-vis analyses. The FESEM and TEM images showed spherical Ag-NPs with size of 25 nm. The hypoglycemic influence of Ag-NPs using Galega officinalis extract is reported for the first time in this study. Blood concentration of liver enzymes, urea, glucose, white blood cells count and TNF-α mRNA levels in visceral adipose tissue significantly declined in diabetic rats receiving Ag-NPs. The synthesized Ag-NPs using Galega officinalis extract may improve complication of diabetes via preventing liver hepatocyte damage and reducing inflammatory factors.

Polyethylenimine (PEI) is one of the most-extensively investigated cationic polymers for gene and drug delivery. Recently, great attention has been directed to design of carriers for co-delivery of nucleic acids and small molecules. These delivery systems are able to overcome the limitations of gene or drug delivery alone. The aim of this study is to prepare a targeted nano-carrier for co-delivery of doxorubicin (Dox) and gene using polyethylenimine. In order to prepare the ligand-containing polymer conjugates, succinic anhydride was conjugated onto the hydroxyl group of Dox through an ester bond following the protection of Dox amines by Fmoc. Drug-polymer conjugates were then coupled with L-DOPA in order to prepare the targeted nanocarriers to the cells through Large Amino Acid Transporter-1 (LAT-1). The PEI derivatives were characterized using 1H-NMR. The toxicity of conjugated polymer, Dox and PEI was assessed on HepG2 and A375 cell lines with different expression level of LAT-1 transporters using MTT assay. The chemical structure of PEI conjugate was confirmed by 1H-NMR. The cytotoxicity measurement demonstrated a cell line-dependent toxicity profile at the concentrations tested in this study. It was shown that there was no significant difference in cell-induced toxicity between conjugated polymer and its parent form in A375 cell line while the cytotoxicity of conjugated polymer was significantly lower than the parent PEI in HepG2 cells. These results provide promising evidence for further evaluation of PEI conjugate for co-delivery of drug and gene via LAT-1 transporters.

Bacillus anthracis is the cause of the fatal anthrax. Available anthrax vaccines have low stability and require multiple injections in order to be effective. Poly lactic acid (PLA) has been approved as a biodegradable and biocompatible polymer for drug and vaccine delivery applications. The purpose of this study is to evaluate the antibody titer against the protective antigen recombinant protein (PA63) encapsulated by the mPEG-PLA double-block copolymers and to compare with the non-encapsulated PA63. To attain this purpose, to start, the desired protein was purified and confirmed and then PA63 was encapsulated with mPEG-PLA double-block copolymers using a water- oil- water solvent evaporation method. Produced nanoparticles was characterized in terms of morphological specifications using scanning electron microscopy, size and polydispersity index using dynamic light scattering and zeta potential using a zeta seizer. The synthesized nanoparticle antigenic content and also its antigen release profile was measured. In the following, the nanoparticles containing antigens (PA63-NPs), blank nanoparticles (mPEG-PLA- NPs), PA63 and adjuvant control were injected subcutaneously to mice and the IgG polyclonal antibody titr was measured by indirect ELISA. Finally to evaluate biocompatibility and toxicity, synthesized nanoparticles were investigated  by cell culture testing.  The results of this study showed that the synthesized nanoparticles are of good quality. ELISA results showed that antibody production titr in mice receiving PA63-NPs was higher than those receiving the PA63 (P<0.05). Cell culture results revealed that the synthesized nanoparticles have no toxicity. The findings of the study indicated that the obtained nano vaccine formulations had a higher ability than non-encapsulated recombinant proteins to stimulate the immune system of animal, and that PLA could be used as an appropriate carrier for an effective, stable, safe and biodegradable engineered recombinant vaccine against anthrax.

Successful detection of tumors in the early stages can significantly increase a patient’s healing process and recovery speed. Conventional imaging techniques usually depend on the tissues’ anatomical structure. Epidermal growth factor receptor-2 (HER-2) is a transmembrane protein with an extracellular ligand-binding domain. HER2 plays an essential role in cell proliferation, differentiation, and survival, and its overexpression is associated with various cancers, especially breast and ovarian cancers. Access to its extracellular domain makes HER2 an ideal target for drug preparation and molecular imaging probes. In this study, a targeted magnetic nanoprobe for molecular imaging of HER2 positive cancers was synthesized, and also its potential as a T2-weighted targeted contrast agent was assessed. Superparamagnetic SPION nanoparticles were synthesized using the co-precipitation method in the presence of CMD and were labeled with SLTVSPWY peptide. The SPION@CMD@SLTVSPWY nanocomplex was characterized by TEM, DLS, XRD, AAS, FTIR, EDX, and VSM. The r1 and r2 relaxivities were then calculated using a 1.5 Tesla clinical magnetic field. The cytotoxicity of the nanocomplex was evaluated by MTT assay. Finally, the difference between uptake of targeted nanocomplexes and SPION by the human SKOV-3 cell line (HER2 +) was investigated. The SPION@CMD NPs were synthesized with spherical shape and superparamagnetic behavior. Characterization results confirmed the formation of SPION@CMD@SLTVSPWY.  r2 relaxivity and r2/r1 calculations resulted in suitable values of 313 mM-1s-1 and 8.05 for SPION@CMD@SLTVSPWY, respectively. Increased uptake of targeted nanocomplexed (SPION@CMD@SLTVSPWY) compared to non-targeted NPs (SPION@CMD) was very noticeable visually, and its numerical ratio was 3.51 at a concentration of 0.075 mM.   The targeted synthesized nanocomplex in this study has great potential as a T2 weighted probe contrast agent in MR imaging owing to its appropriate high uptake in HER2 + cells.

Saffron, the dehydrated stigma of the Crocus sativus L. flower, has been reputed as an effective anticancer and chemopreventive agent in cancer therapy. This study aimed to design PEGylated nanoliposomes containing crude extract of saffron for the treatment of cancer. Various PEGylated nanoliposomes containing 25 mg/ml aqueous extract of saffron were prepared using the thin lipid film method. The characterization of liposomes was indicated by their size, in vitro cytotoxicity, and in vivo therapeutic efficacy against C26 tumor-bearing mice.   By increasing cholesterol levels, the IC50 values of the formulations increased. Liposome characterization illustrated the properties of formulation of choice, as follows: Z-average size: 73.7 ± 1.3 nm; PDI: 0.103 ± 0.035; zeta potential: -20.8 mV ± 3.7; % encapsulation: 91 ± 0.059, % release after 168 hours in 30% FBS: 16.26 ± 0.01. Treating tumor-bearing mice with the selected saffron liposomes indicated that, for the first time, the i.v. injection of nano-liposomal saffron at a dose of 300 mg/kg significantly increased the anti-tumor property compared to the negative control group, while no significant difference was observed compared with aqueous extract of saffron. Hence, to achieve an optimal formulation for human use, the formulation merits further study.

Cancer is known as one of the most life-threatening diseases in the world. Early diagnosis of cancer may significantly increase the chance of effective treatment. In the recent years, the importance of medical imaging usage has been increased to identify cancer’s nature and pattern of growth in order to provide the most advantageous treatment approaches for cancer tumors. Magnetic resonance imaging is an efficient non-invasive tool for early diagnosis of cancer which provides clear scans of various tissues without radiation. Contrast Agents such as Gadoterate Meglumine enhance contrast MR imaging and provide imaging from inside the cells without entering them. In this study, Gadoterate Meglumine nano-sized anionic linear globular dendrimer second generation was first synthesized and then qualitative and quantitative methods were carried out to ensure the proper synthesis and to assess the toxicity of the compound. Once the non-toxicity of the chemical was ensured, in vivo MR imaging studies was performed to test the impact of the synthesized compound on the resolution of image. The result obtained from this study demonstrated that the attachment of Gadolinium (III) to a nano dendrimer reduces its cytotoxicity and also improved resolution of image. In this research, Gadoterate Meglumine nano-sized anionic linear globular dendrimer second generation was effectively able to enter the cells while showing low cytotoxicity in the normal cells and moderate cytotoxicity on cancer cells. Therefore, ALGDG2-GM could be introduced as a novel, safe, effective and promising nano-sized theranostic contrast agent candidate.