ABSTRACT
Calcium-based biomaterials have been intensively studied in the field of drug delivery owing to their excellent biocompatibility and biodegradability. Calcium-based materials can also deliver contrast agents, which can enhance real-time imaging and exert a Ca2+-interfering therapeutic effect. Based on these characteristics, amorphous calcium carbonate (ACC), as a brunch of calcium-based biomaterials, has the potential to become a widely used biomaterial. Highly functional ACC can be either discovered in natural organisms or obtained by chemical synthesis However, the standalone presence of ACC is unstable in vivo. Additives are required to be used as stabilizers or core-shell structures formed by permeable layers or lipids with modified molecules constructed to maintain the stability of ACC until the ACC carrier reaches its destination. ACC has high chemical instability and can produce biocompatible products when exposed to an acidic condition in vivo, such as Ca2+ with an immune-regulating ability and CO2 with an imaging-enhancing ability. Owing to these characteristics, ACC has been studied for self-sacrificing templates of carrier construction, targeted delivery of oncology drugs, immunomodulation, tumor imaging, tissue engineering, and calcium supplementation. Emphasis in this paper has been placed on the origin, structural features, and multiple applications of ACC. Meanwhile, ACC faces many challenges in clinical translation, and long-term basic research is required to overcome these challenges. We hope that this study will contribute to future innovative research on ACC.
ABSTRACT
OBJECTIVE: To prepare hyaluronic acid(HA)-modified breast cancer microenvironment respond nanoparticles and investigate their physicochemical properties as well as in vitro function. METHODS: The polymer HA-PASP was prepared by linking HA with polyaspartic acid (PASP) through a hydrazone bond. Polyethylene glycol (PEG) was used as contrast material for PEG-PASP. Using Doxorubicin(DOX) as a model drug, HA-PASP-NPs@DOX and PEG-PASP-NPs@DOX were prepared by dialysis method. Particle size, morphology and Zeta potential of nanoparticles were observed by particle size tester and transmission electron microscope (TEM). The physical and chemical properties of nanoparticles were evaluated including encapsulation efficiency, drug loading, stability and drug release ability. In vitro function was evaluated including breast cancer cell targeting and tumor microenvironmental response. RESULTS: HA-PASP-NPs@DOX was spherical and uniform, size was (143±21) nm and Zeta potential was (-27.8±3.8) mV, encapsulation efficiency was 28.3% and drug loading was 5.2%. Under pH 7.4, the structure of nanoparticles was stable for more than 30 d, but under pH 6.5 the drug release up to 96%. HA-PASP-NPs@DOX was targeted to MDA-MB-231 cells, which increased DOX uptake by tumor cells. CONCLUSION: The HA-PASP-NPs@DOX could be successfully prepared by dialysis method, which target breast cancer cells and release drugs efficiently in an acidic environment, what′s more, increase cytotoxicity activity.
ABSTRACT
As a part of novel drug delivery carriers, peptides have diverse biological activities, low immunogenicity and good biocompatibility. In recent years, studies on the delivery carriers modified by peptides have attracted much attention. Among them, the peptides with acid sensitivity can change their secondary structures under slightly acidic microenvironment of the tumor or in lysosome. Therefore, the carriers made or modified by acid-sensitive peptides can specifically release the loaded drug in the tumor tissue, enhance the cell internalization of drugs and improve its therapeutic effects. In accordance with acid-sensitive peptides studied, the side chains, number of polar residues, sequence and secondary structure of the peptides might be involved in the acid sensitivity. In this review, we summarize the acid-sensitive peptides from recent literatures, analyze the connection between the structure and the acid sensitivity, and focus on the mechanism and application of acid-sensitive peptides in drug delivery. This provides the basis for further development and utilization for acid-sensitive peptides for efficient drug delivery.