Cationic liposomes as a drug-free system for efficient anticancer therapy by intracytoplasmic delivery of sodium bicarbonate.

Developing the delivery systems with high therapeutic efficacy and low side effects is of great interest and significance for anticancer therapy. Compared to the high cost in synthesizing new chemotherapeutic drugs, exploring the anticancer potentials of existing chemicals is more convenient and efficient. Sodium bicarbonate (BC), a simple inorganic salt, has shown its tumor inhibition capacity via regulating the acidity of tumor microenvironment. However, the effects of intracytoplasmic BC on tumor growth and the potentials of BC to serve as an anticancer agent are still unknown. Herein, we developed a BC-loaded cationic liposome system (BC-CLP) to deliver BC into the cytosol of cancer cells. The in vitro studies showed that the BC-CLP containing 1% BC (w/v) had a size of 112.9 nm and a zeta potential of 19.1 mV, which reduced the viability of the model cancer cells (human oral squamous cell carcinoma HSC-3 cells) to 13.7%. In contrast, the neutral BC-LP caused less than 50% viability reduction. We further found that BC-CLP released BC directly into cytoplasm via membrane fusion pathway rather than endocytosis, leading to the remarkable increase of cytosolic pH, which may contribute to the anticancer effect of BC-CLP. Our findings indicate that BC-CLP is a potential system for high-efficiency cancer therapy without causing drug-related side effects or resistance.

Intratumor delivery of amino-modified graphene oxide as a multifunctional photothermal agent for efficient antitumor phototherapy.

Due to the high selectivity and non-invasive property, phototherapy has attracted increasing attention in the treatment of cancer. Targeted delivery and retention of photoactive agents in tumor tissue is of great significance and importance for safe and efficient phototherapy. Herein, we report a multifunctional nanomaterial photothermal agent, namely amino-modified graphene oxide (AGO) for anti-oral cancer photothermal therapy (PTT). Compared to the parental graphene oxide (GO) which has a negative charge and weak photothermal effect, AGO possesses a positive charge (∼+50 mV) and the significantly enhanced photothermal effect. Positive charge allows AGO to efficiently interact with tumor cells and retain in tumor tissue after intratumor injection. The enhanced photothermal effect allows AGO to achieve the tunable and efficient PTT. In vitro results show that AGO (15 µg/mL) reduces the viability of HSC-3 cells (oral squamous cell carcinoma cell line) to 5% under near infrared (NIR) irradiation (temperature increased to 58.4 °C). In vivo antitumor study shows that intratumor delivery of AGO (200 µg/mouse) has no inhibition effects on tumor growth (454% of initial tumor size) without NIR. With a single dose of NIR irradiation, however, AGO significantly reduces the tumor size to 25% of initial size in 1 of 4 mice, and even induces the complete tumor ablation in 3 of 4 mice. Furthermore, the injected AGO falls off along with the scab after PTT. Our findings indicate that AGO is a potential nano-photothermal agent for tunable, convenient and efficient anticancer PTT.

Understanding the sheet size-antibacterial activity relationship of graphene oxide and the nano-bio interaction-based physical mechanisms.

The antibiotics-independent antimicrobial activity of graphene oxide (GO) is of great importance since antibiotic therapy is facing great challenges from drug resistance. However, the relations of GO size with its antimicrobial activity and how the size regulates the antibacterial mechanisms are still unknown. Herein, we fabricated four GO suspensions with different sizes and demonstrated the parabolic relationship between GO size and its antibacterial activity against the Gram-positive cariogenic bacterium Streptococcus mutans. More interestingly, we found out how GO size regulated the nano-bio interaction-based physical antibacterial mechanisms. Increasing the size reduced the cutting effect but enhanced the cell entrapment effect, and vice versa. In conclusion, GO size affects its edge density and lateral dimension, further regulates its physical antibacterial mechanisms in different orientations and ultimately determines its activity. These findings provide a deep understanding of GO antibacterial property and may guide the design and development of GO for clinical use.

Graphene-based nanomaterials: the promising active agents for antibiotics-independent antibacterial applications.

Graphene-based nanomaterials, such as graphene oxide (GO) and reduced graphene oxide (rGO), have shown great potentials in drug delivery and photodynamic/photothermal therapy due to their featured structure and physicochemical properties. In recent years, their antibacterial potentials have also been exploited. The commonly recognized antibacterial mechanisms include sharp edge-mediated cutting effect, oxidative stress and cell entrapment. This antibacterial activity is very important for human health. As we know, infection with the pathogenic bacteria, especially the drug-resistant ones, is a great threat to human lives. Thus, the development of the antibiotics-independent and drug-free antibacterial agents is of great importance and significance. Graphene-based nanomaterials are a kind of such antibacterial agents. An insight into their properties and antibacterial mechanisms is necessary before they are developed into real products. Herein, we provide a comprehensive understanding of the antibacterial application of graphene-based nanomaterials via summarizing their antibacterial activities against some typical microbial species and discussing their unique mechanisms. In addition, the side-effects and problems in using these nanomaterials are also discussed.

Functional Nanomaterials and Their Potential Applications in Antibacterial Therapy.

In the past decades, nanomaterials have shown great potential in biomedical fields, especially in drug delivery, imaging and targeted therapy. Recently, the development of novel functional nanomaterials for antibacterial application has attracted much attention. Compared to the traditional direct use of antibiotics, antibacterial nanomaterials either as drug delivery systems or active agents have a higher efficacy and lower side effects. Herein, we will focus on the antibacterial applications of four commonly used nanomaterials, including metal-based nanomaterials, polymeric nanoparticles, graphene oxides or carbon-based nanomaterials and nanogels.