Cancer nanomedicine: a review of nano-therapeutics and challenges ahead.

Cancer is known as the most dangerous disease in the world in terms of mortality and lack of effective treatment. Research on cancer treatment is still active and of great social importance. Since 1930, chemotherapeutics have been used to treat cancer. However, such conventional treatments are associated with pain, side effects, and a lack of targeting. Nanomedicines are an emerging alternative due to their targeting, bioavailability, and low toxicity. Nanoparticles target cancer cells via active and passive mechanisms. Since FDA approval for Doxil®, several nano-therapeutics have been developed, and a few have received approval for use in cancer treatment. Along with liposomes, solid lipid nanoparticles, polymeric nanoparticles, and nanoemulsions, even newer techniques involving extracellular vesicles (EVs) and thermal nanomaterials are now being researched and implemented in practice. This review highlights the evolution and current status of cancer therapy, with a focus on clinical/pre-clinical nanomedicine cancer studies. Insight is also provided into the prospects in this regard.

Protective effect of ethanolic extract of Echinacea purpurea contained nanoparticles on meniscal/ligamentous injury induced osteoarthritis in obese male rats.

Osteoarthritis (OA) is a chronic degenerative joint disease associated with age, mechanical stress, and obesity. Echinacea purpurea is a medicinal plant that shows good anti-inflammatory, antioxidant, and immunomodulatory activities. In this study, Echinacea purpurea ethanol extract nanoparticles (Nano-EE) were prepared by encapsulating Echinacea purpurea ethanol extract (EE) in chitosan-silica nanoparticles. Obesity (OB) in Sprague-Dawley (SD) rats was induced by fed 40% high-fat diet and then anterior cruciate ligament and meniscus injury were performed to induce OA. The rats got different doses of samples by oral gavage. The encapsulation efficiency and loading capacity of Nano-EE were 69.1% and 36.1%, respectively. The average size, polydispersity index (PDI), and zeta potential (ZP) of the Nano-EE were 145 ± 11 nm, 0.24 ± 0.01, - 4.57 ± 0.44 mV, respectively. Furthermore, electron microscopic images showed that the particles were spherical and were slightly agglomerated. Moreover, it showed that the leptin content, expression of MMPs, cytokines level, NF-κB level, and iNOS production were decreased whereas collagen II expression was increased after treatment. Besides, Nano-EE ameliorated the pain caused by OA and reduced the proteoglycan loss in cartilage. These results indicated that encapsulated EE (Nano-EE) can ameliorate OA with a low dosage and are more effective than unencapsulated EE.

In-Vitro Antibacterial and Anti-Inflammatory Effects of Surfactin-Loaded Nanoparticles for Periodontitis Treatment.

Periodontitis is an inflammatory disease associated with biofilm formation and gingival recession. The practice of nanotechnology in the clinical field is increased overtime due to its potential advantages in drug delivery applications. Nanoparticles can deliver drugs into the targeted area with high efficiency and cause less damages to the tissues. In this study, we investigated the antibacterial and anti-inflammatory properties of surfactin-loaded κ-carrageenan oligosaccharides linked cellulose nanofibers (CO-CNF) nanoparticles. Three types of surfactin-loaded nanoparticles were prepared based on the increasing concentration of surfactin such as 50SNPs (50 mg surfactin-loaded CO-CNF nanoparticles), 100SNPs (100 mg surfactin-loaded CO-CNF nanoparticles), and 200SNPs (200 mg surfactin-loaded CO-CNF nanoparticles). The results showed that the nanoparticles inhibited the growth of Fusobacterium nucleatum and Pseudomonas aeruginosa. The reduction in biofilm formation and metabolic activity of the bacteria were confirmed by crystal violet and MTT assay, respectively. Besides, an increase in oxidative stress was also observed in bacteria. Furthermore, anti-inflammatory effects of surfactin-loaded CO-CNF nanoparticles was observed in lipopolysaccharide (LPS)-stimulated human gingival fibroblast (HGF) cells. A decrease in the production of reactive oxygen species (ROS), transcription factor, and cytokines were observed in the presence of nanoparticles. Collectively, these observations supported the use of surfactin-loaded CO-CNF as a potential candidate for periodontitis management.

Protective effects of Antrodia camphorata extract against hypoxic cell injury and ischemic stroke brain damage.

Ischemic stroke is the most prevalent stroke condition in the world resulted in either a transient ischemic attack or long-lasting neurological problems due to the interrupted or reduced blood flow to the brain. Antrodia camphorata is a well-known medicinal mushroom native to Taiwan and is familiar due to its medicinal effects. The current study investigated the protective effect of A. camphorata-alcohol extracts (AC-AE) against cobalt (II) chloride (CoCl2 )-induced oxidative stress in vitro and ischemia/reperfusion-induced brain injury in vivo. The rats were pre-treated with AC-AE for 4 weeks. Our results showed that AC-AE reduced cell damage and decreased reactive oxygen species (ROS) production in C6 and PC12 cells under CoCl2 -induced hypoxic condition. AC-AE doses (385, 770, 1,540 mg/kg/day, 4 weeks) increased nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) mRNA expressions and decreased inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA expressions in Sprague Dawley rat. Besides, it decreased stroke infarct size and increased the level of antioxidants in both brain and serum. Furthermore, it reduced the formation of malondialdehyde (MDA) after ischemia/reperfusion (I/R). Our results suggested that AC-AE exerted an effective reduction of ischemia stroke by regulating ROS production.

Therapeutic effects of antibiotics loaded cellulose nanofiber and κ-carrageenan oligosaccharide composite hydrogels for periodontitis treatment.

Periodontitis is an inflammatory disease that can lead to the periodontal pocket formation and tooth loss. This study was aimed to develop antimicrobials loaded hydrogels composed of cellulose nanofibers (CNF) and κ-carrageenan oligosaccharides (CO) nanoparticles for the treatment of periodontitis. Two antimicrobial agents such as surfactin and Herbmedotcin were selected as the therapeutic agents and the hydrogels were formulated based on the increasing concentration of surfactin. The proposed material has high thermal stability, controlled release, and water absorption capacity. This study was proceeded by investigating the in vitro antibacterial and anti-inflammatory properties of the hydrogels. This material has strong antibacterial activity against periodontal pathogens such as Streptococcus mutans, Porphyromonas gingivalis, Fusobacterium nucleatum, and Pseudomonas aeruginosa. Moreover, a significant increase in malondialdehyde (MDA) production and a decrease in biofilm formation and metabolic activity of the bacteria was observed in the presence of hydrogel. Besides, it reduced the reactive oxygen species (ROS) generation, transcription factor, and cytokines production in human gingival fibroblast cells (HGF) under inflammatory conditions. In conclusion, the hydrogels were successfully developed and proven to have antibacterial and anti-inflammatory properties for the treatment of periodontitis. Thus, it can be used as an excellent candidate for periodontitis treatment.

Surfactin-Loaded ĸ-Carrageenan Oligosaccharides Entangled Cellulose Nanofibers as a Versatile Vehicle Against Periodontal Pathogens.

PURPOSE: Periodontitis is a chronic inflammatory disease associated with microbial accumulation. The purpose of this study was to reuse the agricultural waste to produce cellulose nanofibers (CNF) and further modification of the CNF with κ-carrageenan oligosaccharides (CO) for drug delivery. In addition, this study is focused on the antimicrobial activity of surfactin-loaded CO-CNF towards periodontal pathogens. MATERIALS AND METHODS: A chemo-mechanical method was used to extract the CNF and the modification was done by using CO. The studies were further proceeded by adding different quantities of surfactin [50 mg (50 SNPs), 100 mg (100 SNPs), 200 mg (200 SNPs)] into the carrier (CO-CNF). The obtained materials were characterized, and the antimicrobial activity of surfactin-loaded CO-CNF was evaluated. RESULTS: The obtained average size of CNF and CO-CNF after ultrasonication was 263 nm and 330 nm, respectively. Microscopic studies suggested that the CNF has a short diameter with long length and CO became cross-linked to form as beads within the CNF network. The addition of CO improved the degradation temperature, crystallinity, and swelling property of CNF. The material has a controlled drug release, and the entrapment efficiency and loading capacity of the drug were 53.15 ± 2.36% and 36.72 ± 1.24%, respectively. It has antioxidant activity and inhibited the growth of periodontal pathogens such as Streptococcus mutans and Porphyromonas gingivalis by preventing the biofilm formation, reducing the metabolic activity, and promoting the oxidative stress. CONCLUSION: The study showed the successful extraction of CNF and modification with CO improved the physical parameters of the CNF. In addition, surfactin-loaded CO-CNF has potential antimicrobial activity against periodontal pathogens. The obtained biomaterial is economically valuable and has great potential for biomedical applications.

Curcumin-Loaded Mesoporous Silica Nanoparticles Markedly Enhanced Cytotoxicity in Hepatocellular Carcinoma Cells.

Curcumin, a natural polyphenol extracted from a perennial herb Curcuma longa has been verified for many physiological activities such as anti-oxidant, anti-inflammatory, and anti-tumor properties. The direct use of curcumin cytotoxicity studies are limited due to its unstable chemical structure, low bioavailability, easy oxidation, and degradation by ultraviolet (UV) light etc. Trying to overcome this problem, silica-encapsulated curcumin nanoparticles (SCNP) and chitosan with silica co-encapsulated curcumin nanoparticles (CSCNP) were prepared by silicification and biosilicification methods, respectively, and encapsulated curcumin within it. We investigated the antitumor properties of SCNP and CSCNP on different tumor cell lines. Scanning electron microscopy (SEM) analysis revealed that both SCNP and CSCNP were almost spherical in shape and the average particle size of CSCNP was 75.0 ± 14.62 nm, and SCNP was 61.7 ± 23.04 nm. The results show that CSCNP has more anti-oxidant activity as compared to curcumin and SCNP. The higher cytotoxicity towards different cancerous cell lines was also observed in CSCNP treated tumor cells. It was noted that the SCNP and CSCNP has a high percentage of IC50 values in Hep G2 cells. The encapsulation of curcumin improved instability, antioxidant activity, and antitumor activity. Our results demonstrated that nanoencapsulation of curcumin with silica and chitosan not only increase curcumin stability but also enhance its cytotoxic activity on hepatocellular carcinoma cells. On the basis of these primary studies, the curcumin-loaded nanoparticles appear to be promising as an innovative therapeutic material for the treatment of tumors.

Attenuation of reproductive dysfunction in diabetic male rats with timber cultured Antrodia cinnamomea ethanol extract.

Diabetes mellitus together with the oxidative stress affects the process of spermatogenesis and leads to male infertility. Antrodia cinnamomea (AC) is a mushroom found unique in Taiwan and commonly used for the treatment of several types of cancers and inflammatory disorders. This study was aimed to investigate the anti-oxidative and the ameliorative effects of Antrodia cinnamomea ethanol extract (ACEE) on reproduction dysfunction in male diabetic rats. The diabetic condition was induced by administrating the combination of streptozotocin (STZ) (65 mg/kg) and nicotinamide (NA) (230 mg/kg). Three different doses of ACEE were tested (385, 770, 1540 mg/kg) for 5 weeks. The results indicated that the ACEE improved STZ-NA induced hyperglycemia, oxidative stress, and insulin resistance. In addition to this, ACEE reduced the degree of lipid peroxidation, recovered the abnormal structure of the seminiferous tubules, and improved sperm parameters. Moreover, the DNA damages and mitochondrial membrane potential were improved in sperm. Our study confirmed that the ACEE has anti-inflammatory and ameliorative effects to prevent diabetes-induced male reproductive dysfunction.

Effect of Cistanche Tubulosa Extracts on Male Reproductive Function in Streptozotocin⁻Nicotinamide-Induced Diabetic Rats.

Diabetes is a chronic disorder characterized by hyperglycemia due to decreased levels of insulin or the inefficiency of the tissue to use it effectively. Infertility is known as a major outcome of diabetes and affects the male reproductive system by causing sperm impairment and gonadal dysfunction. Cistanche tubulosa is a parasitic plant which has the capacity to improve memory, immunity, and sexual ability, reduce impotence, and minimize constipation. This study was focused on the investigation of the anti-inflammatory and protective effects of echinacoside (ECH) in Cistanche tubulosa extract (CTE) on the male reproductive system of the diabetic rats. The antioxidant, anti-inflammatory, and protective effects of CTE were evaluated by both in vitro and in vivo methods. The in vitro results show that the ECH inhibited reactive oxygen species (ROS) production and improved StAR, CYP11A1, CYP17A1, and HSD17ß3 protein expression. The in vivo analysis was carried out with three doses of echinacoside (ECH) (80, 160, and 320 mg/kg) in CTE. In total, 0.571 mg/kg of rosiglitazone (RSG) was administered as a positive control. Diabetes was induced by streptozotocin (STZ) (65 mg/kg) and nicotinamide (230 mg/kg) in combination with a high-fat diet (45%). The in vivo studies confirmed that the ECH improved blood sugar levels, insulin resistance, leptin resistance, and lipid peroxidation. It can restore kisspeptin 1 (KiSS1), G protein-coupled receptor GPR 54, suppressor of cytokine signaling 3 (SOCS-3), and sirtuin 1 (SIRT1) messenger ribonucleic acid (mRNA) expression in the hypothalamus and recover sex hormone level. Thus, this study confirmed the antioxidant, anti-inflammatory, and steroidogenesis effects of CTE.

Amelioration effects of nanoencapsulated triterpenoids from petri dish-cultured Antrodia cinnamomea on reproductive function of diabetic male rats.

PURPOSE: Nanoencapsulated triterpenoids from petri dish-cultured Antrodia cinnamomea (PAC) and its amelioration effects on reproductive function in diabetic rats were investigated. MATERIALS AND METHODS: PAC encapsulated in silica-chitosan nanoparticles (Nano-PAC) was prepared by the biosilicification method. The diabetic condition in male Sprague Dawley rats was induced by high-fat diet and streptozotocin (STZ). Three different doses of Nano-PAC (4, 8, and 20 mg/kg) were administered for 6 weeks. Metformin and control of nanoparticles (Nano-con) were taken as positive and negative controls, respectively. RESULTS: The average particle size was ~79.46±1.63 nm, and encapsulation efficiency was ~73.35%±0.09%. Nano-PAC administration improved hyperglycemia and insulin resistance. In addition, Nano-PAC ameliorated the morphology of testicular seminiferous tubules, sperm morphology, motility, ROS production, and mitochondrial membrane potential. Superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) antioxidant, as well as testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) were increased, whereas proinflammatory cytokines TNF-α, IL-6, and IFN-γ were decreased. CONCLUSION: In the present study, we successfully nanoencapsulated PAC and found that a very low dosage of Nano-PAC exhibited amelioration effects on the reproductive function of diabetic rats.

Modulation of Diabetes Mellitus-Induced Male Rat Reproductive Dysfunction with Micro-Nanoencapsulated Echinacea purpurea Ethanol Extract.

Diabetes mellitus is a major health problem that affects a patient's life quality throughout the world due to its worst complications. It was recognized that chronic hyperglycemia with oxidative stress was the major cause of male infertility. Echinacea purpurea ethanol extract (EE) contains phenolic acid and isobutylamides had been proven to ameliorate diabetic complications. Chitosan/silica nanoparticles are well-known in the medicinal field because of its controlled release and drug delivery properties. This study was aimed at investigating whether the EE encapsulated chitosan/silica nanoparticle (nano-EE) can enhance the amelioration of male infertility. Our results indicated that the average size of nano-EE was 218 ± 42 nm with an encapsulation efficiency of 66.9% and loading capacity of 39.9%. The reduction in oxidative stress and antioxidant activity of nano-EE was observed in LC-540 cells. In in vivo experiment, 33 mg/kg of streptozotocin (STZ) was used to induce diabetes in male Sprague-Dawley rats. Diabetic rats were treated with nano (465 mg/kg), nano-EE 1 (93mg/kg), nano-EE3 (279mg/kg), nano-EE5 (465 mg/kg), and metformin (Met) (200 mg/kg) for 7 weeks. The results show that the nano-EE5 can improve hyperglycemia, insulin resistance, and plasma fibroblast growth factor 21 (FGF 21) resistance. It was also confirmed that nano-EE5 significantly improved the testis tissue structure, increasing sperm quality and DNA integrity as well as reducing reactive oxygen species level.