Abstract:Nanobiomedicine: A New Frontier for Interdisciplinary

Abstract:The research on nanozyme which is a novel enzyme mimic based on nanomaterial, is becoming a rapidly emerging field since ferromagnetic nanoparticles with intrinsic peroxidase-like activity was first reported in 2007. Many nanozymes with different morphologies, sizes and components are found to have intrinsic enzyme-like activities and their catalytic mechanisms are systematically investigated. Nanozyme demonstrates high efficient activity, stability and low cost by preparation at large scale. Therefore, nanozymes have promising and multiple applications in many important fields, such as biomedicine, chemical industry, food, agriculture and environment. The discovery of nanozyme not only promotes the basic research in nanotechnology, but also expands the applications of nanomaterials. This review will introduce the latest research progresses in the field of nanozyme.

Abstract:Magnetic nanoparticles that have magnetic properties and other functionalities, have a broad application prospects in many fields, especially in biomedicine and bioengineering. In this review, chemical design and synthesis, as well as the surface functional strategy of magnetic nanoparticles are presented. The biomedical applications, such as magnetic resonance imaging, magnetic-controlled therapy, magnetic hyperthermia, and bio-separation, are also discussed.

Abstract:Cell membrane is a thin semi-permeable membrane that surrounds the cytoplasm and protects the homeostasis of internal components of a cell, which is also involved in a variety of molecular biological processes such as cell adhesion, ion conductivity and cell signaling. Model cell membrane may provide an efficient alternative for studying these processes. Hence, studying the interactions between medical nanoparticles and model cell membrane may play an important role in evaluating the biosafety of nanoparticles and promoting the biomedical applications of nanoparticles. In this paper, we reviewed the recent progresses of simulation studies of the interactions between medical nanoparticles and model cell membrane. And on this basis, we proposed the future research directions considering the focuses of modern membrane biophysics.

Abstract:Rare earth upconversion fluorescent nanomaterials have drawn great attention as novel fluorescent probes because of their many unique merits, such as superior photostability, narrow emission spectra, long lifetime and larger Stokes shift. By using near infrared laser as excitation light source, it is feasible for the upconversion fluorescent nanomaterials as excellent fluorescent probes for in vivo fluorescence imaging due to the high light penetration depth in biological tissues, absence of photodamage to live organisms, low autofluorescence background. Recent progress of preparation and biological application of rare earth upconversion fluorescent nanomaterials is reviewed in this paper.

Abstract:As a main inorganic component of the human bone, hydroxyapatite (HA) is widely used in hard tissue repair and replacement. With high surface area and excellent fluidity, HA microspheres have gained extensive interests for biomedical applications. This article reviews the synthesis of HA microspheres with nanostructures, with a special focus on the use of soft and hard templates. The formation mechanism of these microspheres and related nanostructures are also discussed in detail. Problems in current synthesis methods are identified and the future trends of this emerging field are also discussed.

Abstract:We developed one-step self-assembly method to prepare poly(ethylene glycol)-phosphatidylethanolamine (PEG-PE) micelles, which had core-shell structure and particle size at 20 nm. Drug-loaded PEG-PE micelles displayed better stability than empty micelles in vitro and in vivo because the drug/polymer interactions reinforced the micellular structure. Drugs distributed at the core-shell interface of PEG-PE micelles without changing micellar size. Our studies demonstrated that physico-chemical properties of drugs determined their self-assembly mechanism with polymers and the release profiles of drugs from micelles in vitro. Encapsulation of drugs in micelles increased their cellular accumulation due to the increased membrane fluidity caused by PEG-PE insertion, which did not affect cell membrane permeability and integrity. Compared to free drugs, anticancer drugs encapsulated into PEG-PE micelles demonstrated an increased antitumor efficiency in vivo and an extended life span of mice by EPR effect of PEG-PE micelles. On the other hand, PEG-PE micelles maintained higher drug concentrations in lymphatic systems, thus resulting in significantly antitumor effects for metastatic tumors with less lung metastasis. PEG-PE is an FDA-approved nonionic diblock copolymer with good biocompatibility and safety. As drug delivery systems, PEG-PE micelles has a wide developmental future.

Abstract:Circulating tumor cells (CTC) in the blood is the tumor cells surviving in the process of tumor metastasis, which is considered to be the prerequisite to the metastasis tumor. The presence and the number of CTC is important to evaluate the tumor prognosis, monitor and evaluate the curative effect of tumor metastasis. In recent years, nanomaterials, nanostructured surface combined with microfluidic technology is widely used in CTC enrichment and detection. Now we review the latest nanotechnology progress on the enrichment and detection of CTC, hoping to provide help for the diagnosis and treatment of tumor.

Abstract:The quantum dots (QDs) will have biological function by surface modification with biomolecules or drug molecules. The functionalized QDs have been widely applied in biomedical optical diagnosis and therapy for their unique optical propriety and biocompatibility. This paper introduced the synthesis and modification methods of functionalized QDs, and summarized their applications for tumor in vivo diagnosis and therapy, including in vivo lymph node imaging, blood vessel dynamic imaging, tumor imaging and anti-tumor drug tracking, et al. Finally, we also discussed the perspective and the challenge of the functionalized QDs utilization for the tumor in vivo diagnosis and therapy.

Abstract:Indocyanine green (ICG) is a conventional near-infrared (NIR) dye that can be used in clinical fluorescence imaging, and it is also an effective light absorber for laser-mediated photothermal or photodynamic therapy. However, the ICG is still limited by its unstable properties in aqueous media and quick clearance from the body. The ICG-loaded nanoparticle has provided the versatile assembly tools for further development and application of the ICG. Herein, we review the application of ICG nanoparticles in NIR diagnosis and photothermal/photodynamic therapy of cancer.

Abstract:The noble metal clusters is a new class of fluorescent material. With a set of attractive features, such as ultrasmall size, fluorescence tenability and good biocompatibility, the clusters are ideal candidate for the fluorescent labels and detection. In this review, we summarize the synthesis and fluorescence characteristic of the clusters, and the recent development of their application in bioimging and in vitro detection.

Abstract:In tumors, the blood supply is anisotropic spatially and temporally, meanwhile the vascular permeability is high and the ability of fluid flowing from lymphangion is poor. These factors work together to create tumor microenvironment and block therapeutic agents from uniformly delivering into tumors. Compared to conventional medicine, nanomedicine has the potential to enable the preferential delivery of drugs to tumor, deliver more than one therapeutic agent, and bind drugs to target cancer cells specially. But the specific physiological barriers presented in tumor hinder efficient and uniform delivery of nanoparticles into tumors. This may be account for moderate survival benefit obtained from FDA-approved nanomedicines. Here, we summarize these barriers existing in cancer therapy and researches aiming at conquering these barriers. Finally, we discuss factors in nanoparticles design to improve delivering efficiency for tumor.

Abstract:Gene therapy has rapidly emerged as a promising method for the treatment of numerous diseases. However, the intrinsic deficiencies of gene-based drugs, such as enzymatic degradation in the body, poor membrane penetrability and lack of target ability, have limited the development of its therapeutic application. Herein, it is important for efficient gene therapy to develop efficient and safe gene vectors that can deliver the gene-based drugs to targeted cells. This paper reviews the current development in gene delivery vectors, especially summarizes the characteristic and development of viral vectors, non-viral vectors and nanoparticles with tracing ability.

Abstract:Lipid nanoparticles are prepared with solid fatty acids or esters, which is widely concerned in drug delivery due to their good biocompatiblity and safety. The oral bioavailability of poor-soluble drugs, peptides and proteins are very low because of their poor solubility, permeability or stability. However, lipid nanoparticles as their carrier can improve the oral bioavailability significantly, which enhance the application or investigation of lipid nanoparticles as oral drug delivery systems. This paper reviews the four aspects of lipid nanoparticles, including formualtion, preparation, absorption mechanism and application in oral delivery.

Abstract:Mesoporous silica materials have attracted much attention for their potential biomedical applications due to their tailored mesoporous structure, large surface area, good biocompatibility, and the ease of surface functionalization. In the past few years, the mesoporous silica based drug nanocarriers have become the research focus of many researchers. This article reviews the recent research advances of mesoporous silica based multifunctional drug delivery systems with targeting modification and bioimaging, and details the design, surface modification, and applications in drug delivery field of mesoporous silica based drug delivery systems with diverse morphologies (such as hollow/rattle-type, nanotubes, etc.). Finally, we analyze the existing problems in practical applications and outlook the future development trends of mesoporous silica based drug delivery systems (including the specific morphological, multifunctional hybrid, and biodegradable mesoporous silica drug delivery systems).

Abstract:Skin is the largest organ of human offering important pathway for drug delivery. Drug delivery through transdermal pathway have to penetrate through the skin tissue to realize absorption, thereinto, stratum corneum turns out to be the largest barrier to accomplish transdermal drug delivery. Owing to the specific interactions between nano-formulations and skin tissue, transdermal nanocarrier could provide advantages, such as improving skin penetrating efficiency, sustaining release, avoiding the first-pass effect, decreasing side effects, etc. The structures and components of nano-formulations play crucial roles in enhancing skin penetration. A better and more comprehensive understanding of the correlations between them is not only favorable for the design of novel transdermal nanocarrier, but also beneficial to establish safe, efficient and functional transdermal drug delivery system.

Abstract:For the past few years, thermosensitive hydrogels have been widely used in biomedical field including drug delivery system, tissue engineering and so on. Thermosensitive hydrogels formed with micelles assembled by amphiphilic block polymer based on polyethyleneglycol (PEG) and biodegradable polyesters play an important role among these hydrogels. In the present review, we summarize the effects of molecular weight, sequence of segments, ratio between hydrophilic and hydrophobic block and structure of hydrophobic block on the thermosensitive behavior of aqueous solution of amphiphilic block polymer synthesized by PEG and ε-polycaprolactone. The progresses of the thermosensitive hydrogel in the local drug delivery are also explored.

Abstract:Environment-responsive polymeric nanoparticles as antitumor drug delivery systems could response to tiny environmental stimulus, change their structure and release the antitumor drug. They have been widely applied in biomedical area due to their considerable advantages of prolonging survival time with lower toxicity, controllability and high drug loading in cancer therapy. Here, we present an overview of the recent work on environment-responsive polymeric nanoparticles as drug delivery systems for cancer therapy, including pH sensitive, temperature sensitive, redox sensitive and enzyme sensitive, based on the domestic and international research progress. In addition, recent advances and future directions in the development of environment- responsive polymeric nanoparticles as antitumor drug delivery systems are also included.

Abstract:On account of its unique physicochemical properties, magnetic nanoparticles attracts many attentions in its applications of tissue engineering. Here, we briefly described two major characteristics of magnetic nanoparticles, surface chemical activity and the magnetic properties. The main synthesis methods of magnetic nanoparticles in biomedicine was included. Based on the two major characteristics of magnetic nanoparticles, we mainly reviewed methods of the designing biomaterials in tissue engineering and the assembling growth factors or genes released vector. We also summarized the research progress of mechanical stimulation, stem cell labeling, tracking and cell patterning on the magnetic nanoparticles construction in this paper.

Abstract:Cancer invasion and metastasis remain two root causes of mortality. This process involves alterations of tumor microenvironment, particularly the remodeling of extracellular matrix(ECM), characterized by collagen Ⅳ uncoiling, degradation, fragments deposition and cross-linking. This study was aimed to reveal the cancer invasion mode based on dynamic changes of collagen Ⅳ by novel quantum dots (QDs) imaging technology. Cancer tissues of hepatocellular carcinoma, gastric cancer, breast cancer and cervical carcinoma were collected and stained by traditional immunohistochemistry and novel QDs-based imaging technology. Several key molecules representing of cancer cells and tumor microenvironment were studied, including Ki67, representing of proliferation of cancer cells, macrophages, representing of monocytes infiltration and collagen Ⅳ, representing of tumor stroma remodeling during cancer invasion and migration. During cancer invasion and migration, collagen Ⅳ had structural and functional changes. In different cancer tissues, 4 types of collagen Ⅳ could be observed, consisting of linear, irregular, fragmented and disappeared. However, several common features were evident during the dynamic process of cancer progression. First, collagen Ⅳ at basement membrane increased, presenting an irregular sheath surrounding cancer nests; then, collagen Ⅳ was degraded to form invasion fronts at several sites accompanied with linear re-deposition of collagen Ⅳ and increased macrophages in ECM. Second, cancer cells escaped from large cancer nests to seed in ECM. And also the dynamic changes of collagen Ⅳ were accompanied with the recruitment of macrophages, together to regulate and affect biological behaviors of cancer cells. A series changes caused by dynamic changes of collagen Ⅳ provide a proper tumor microenvironment for cancer invasion and migration. In this dysfunctional tumor microenvironment, tumor mass becomes increasingly harder with tumor stroma stiffening causing high ECM stress. With cancer cells proliferation, tension becomes increasingly higher, till reaching a critical point, where large tumor nests "burst", releasing many tiny seeding nests and reducing the central ECM tension. The resulting seeding tumor nests repeat the same process of tumor mass growth→prominent central hypoxia→collagen Ⅳ cross-linking and deposition→ECM remodeling→ECM stress buildup→tumor nest bursts, leading to accelerated cancer progression in this rich "soil" of dysfunctional tumor microenvironment, presenting a "pulse mode".

Abstract:Recently, liposomes have gained attention as a promising tool for drug and gene delivery. However, their applications have been constrained by their poor stability, aggregation and difficult to functional. Using amphiphilc conjugated linoleic acid modified polylysine (PC) and cholesterol, we developed a novel polymeric liposomes (PLs). These PLs retained the advantages of conventional liposomes (CLs), and overcome the above disadvantages of CLs. In addition, PEG chains coated on the PLs surface can prolong their circulation time in the blood. These results suggest that the PLs were nano-sized, achieved a sustained release of drugs, showed limited cytotoxicity and increased uptake in LN229 glioblastoma cells.

Abstract:Considering the structure and electrophysiological properties of native myocardium, significant progress has been made in cardiac tissue engineering based on nano-conductive materials. Carbon nanotubes possess the good mechanical and electrical properties and previous study have showed carbon nanotubes can promote cardiac cells adhesion, proliferation and maturation, and enhance cell-cell electrical coupling. However, cell behavior of carbon nanotubes on brown adipose-derived cardiac stem cells (CSCs) has not been investigated. Here, we first prepared multiple-walled carbon nanotubes (MWCNTs) / polymethylmethacrylate (PMMA) thin film according to the reported study. And then, we explored the influences of MWNTs/PMMA thin films on cell viability, proliferation and cardiac differentiation of brown adipose-derived CSCs were evaluated. We demonstrated MWNTs/PMMA thin films has no obvious effect on cell viability and proliferation of brown adipose CSCs compared to those on gelatin thin film. Furthermore, we observed brown adipose CSCs on MWNTs/PMMA thin films exhibited significantly higher amounts of α-actinin and connexin43. By transmission electron microscopy, we found that carbon nanotubes were in direct contact with cell membranes and regulated cell behavior. We first explored the influence of carbon nanotubes on brown adipose-derived CSCs and found that carbon nanotubes promoted the cardiac differentiation of brown adipose-derived CSCs. This study may be benefit to promote the therapeutic application of carbon nanotubes in myocardial infarction.