Injectable Hydrogel as a Unique Platform for Antitumor Therapy Targeting Immunosuppressive Tumor Microenvironment

Cancer immunotherapy can boost the immune response of patients to eliminate tumor cells and suppress tumor metastasis and recurrence. However, immunotherapy resistance and the occurrence of severe immune-related adverse effects are clinical challenges that remain to be addressed. The tumor microenvironment plays a crucial role in the therapeutic efficacy of cancer immunotherapy. Injectable hydrogels have emerged as powerful drug delivery platforms offering good biocompatibility and biodegradability, minimal invasion, convenient synthesis, versatility, high drug-loading capacity, controlled drug release, and low toxicity. In this review, we summarize the application of injectable hydrogels as a unique platform for targeting the immunosuppressive tumor microenvironment.

Opportunities and Challenges of Nanoparticles in Digestive Tumours as Anti-Angiogenic Therapies

Digestive tumours, a common kind of malignancy worldwide, have recently led to the most tumour-related deaths. Angiogenesis, the process of forming novel blood vessels from pre-existing vessels, is involved in various physiological and pathological processes in the body. Many studies suggest that abnormal angiogenesis plays an important role in the growth, progression, and metastasis of digestive tumours. Therefore, anti-angiogenic therapy is considered a promising target for improving therapeutic efficacy. Traditional strategies such as bevacizumab and regorafenib can target and block the activity of proangiogenic factors to treat digestive tumours. However, due to resistance and some limitations, such as poor pharmacokinetics, their efficacy is not always satisfactory. In recent years, nanotechnology-based anti-angiogenic therapies have emerged as a new way to treat digestive tumours. Compared with commonly used drugs, nanoparticles show great potential in tumour targeted delivery, controlled drug release, prolonged cycle time, and increased drug bioavailability. Therefore, anti-angiogenic nanoparticles may be an effective complementary therapy to treat digestive tumours. In this review, we outline the different mechanisms of angiogenesis, the effects of nanoparticles on angiogenesis, and their biomedical applications in various kinds of digestive tumours. In addition, the opportunities and challenges are briefly discussed.

Advances in Polyhydroxyalkanoate Nanocarriers for Effective Drug Delivery: An Overview and Challenges

Polyhydroxyalkanoates (PHAs) are natural polymers produced under specific conditions by certain organisms, primarily bacteria, as a source of energy. These up-and-coming bioplastics are an undeniable asset in enhancing the effectiveness of drug delivery systems, which demand characteristics like non-immunogenicity, a sustained and controlled drug release, targeted delivery, as well as a high drug loading capacity. Given their biocompatibility, biodegradability, modifiability, and compatibility with hydrophobic drugs, PHAs often provide a superior alternative to free drug therapy or treatments using other polymeric nanocarriers. The many formulation methods of existing PHA nanocarriers, such as emulsion solvent evaporation, nanoprecipitation, dialysis, and in situ polymerization, are explained in this review. Due to their flexibility that allows for a vessel tailormade to its intended application, PHA nanocarriers have found their place in diverse therapy options like anticancer and anti-infective treatments, which are among the applications of PHA nanocarriers discussed in this article. Despite their many positive attributes, the advancement of PHA nanocarriers to clinical trials of drug delivery applications has been stunted due to the polymers’ natural hydrophobicity, controversial production materials, and high production costs, among others. These challenges are explored in this review, alongside their existing solutions and alternatives.

Current Perspectives on Nanoemulsions in Targeted Drug Delivery

Nanoemulsions are an isotropical mixture of oil, surfactant, and water with droplet diameter approximately in the range of 10-100 nm. They are being exponentially used for drug delivery systems for the influential administration of therapeutical agents because of their potential advantages over other approaches. Nanoemulsions can be used to design delivery systems that have increased drug loading, enhanced drug solubility, increased bioavailability, controlled drug release, and enhanced protection against chemical or enzymatic degradation. Moreover, nanoemulsions have better thermodynamical stability to flocculation, sedimentation, and creaming than conventional emulsions. Their small droplet dimensions and large droplet surface area positively influence drug transport and delivery, along with allowing targeting to specific sites. This chapter focuses on recent applications of nanoemulsions in the area of drug delivery.

Polypropylene Graft Poly(methyl methacrylate) Graft Poly(N-vinylimidazole) as a Smart Material for pH-Controlled Drug Delivery

Surface modification of polypropylene (PP) films was achieved using gamma-irradiation-induced grafting to provide an adequate surface capable of carrying glycopeptide antibiotics. The copolymer was obtained following a versatile two-step route; pristine PP was exposed to gamma rays and grafted with methyl methacrylate (MMA), and afterward, the film was grafted with N-vinylimidazole (NVI) by simultaneous irradiation. Characterization included Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), thermogravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS), and physicochemical analysis of swelling and contact angle. The new material (PP-g-MMA)-g-NVI was loaded with vancomycin to quantify the release by UV-vis spectrophotometry at different pH. The surface of (PP-g-MMA)-g-NVI exhibited pH-responsiveness and moderate hydrophilicity, which are suitable properties for controlled drug release.

Computational Modeling of Combination of Magnetic Hyperthermia and Temperature-Sensitive Liposome for Controlled Drug Release in Solid Tumor

Combination therapy, a treatment modality that combines two or more therapeutic methods, provides a novel pathway for cancer treatment, as it targets the region of interest (ROI) in a characteristically synergistic or additive manner. To date, liposomes are the only nano-drug delivery platforms that have been used in clinical trials. Here, we speculated that it could be promising to improve treatment efficacy and reduce side effects by intravenous administration of thermo-sensitive liposomes loaded with doxorubicin (TSL-Dox) during magnetic hyperthermia (MHT). A multi-scale computational model using the finite element method was developed to simulate both MHT and temperature-sensitive liposome (TSL) delivery to a solid tumor to obtain spatial drug concentration maps and temperature profiles. The results showed that the killing rate of MHT alone was about 15%, which increased to 50% using the suggested combination therapy. The results also revealed that this combination treatment increased the fraction of killed cells (FKCs) inside the tumor compared to conventional chemotherapy by 15% in addition to reducing side effects. Furthermore, the impacts of vessel wall pore size, the time interval between TSL delivery and MHT, and the initial dose of TSLs were also investigated. A considerable reduction in drug accumulation was observed in the tumor by decreasing the vessel wall pore size of the tumor. The results also revealed that the treatment procedure plays an essential role in the therapeutic potential of anti-cancer drugs. The results suggest that the administration of MHT can be beneficial in the TSL delivery system and that it can be employed as a guideline for upcoming preclinical studies.

Engineering Electrospun Nanofibers for the Treatment of Oral Diseases

With the increase of consumption of high-sugar foods, beverages, tobacco, and alcohol, the incidence rate of oral diseases has been increasing year by year. Statistics showed that the prevalence of oral diseases such as dental caries, dental pulpal disease, and periodontal disease has reached as high as 97% in 2015 in China. It is thus urgent to develop functional materials or products for the treatment of oral diseases. Electrospinning has been a widely used technology that is capable of utilizing polymer solution to generate micro/nano fibers under an appropriate high voltage condition. Owing to their excellent structures and biological performances, materials prepared by electrospinning technology have been used for a wide range of oral-related applications, such as tissue restoration, controlled drug release, anti-cancer, etc. In this regard, this article reviews the application and progress of electrospun nanofibers to various oral diseases in recent years. Firstly, engineering strategies of a variety of nanofiber structures together with their resultant functions will be introduced. Then, biological functions of electrospun nanofibers as well as their applications in the treatment of oral diseases are summarized and demonstrated. Finally, the development viewpoint of functional nanofibers is prospected, which is expected to lay the foundation and propose the direction for further clinical application.