Dendrimers are used for a variety of applications in medicine but, due to their host–guest and entrapment characteristics, are particularly used for the delivery of genes and drugs. However, dendrimers are intrinsically toxic, thus creating a major limitation for their use in biological systems. To reduce such toxicity, biocompatible dendrimers have been designed and synthesized, and surface engineering has been used to create advantageous changes at the periphery of dendrimers. Although dendrimers have been reviewed previously in the literature, there has yet to be a systematic and comprehensive review of the harmful effects of dendrimers. In this review, we describe the routes of dendrimer exposure and their distribution in vivo. Then, we discuss the toxicity of dendrimers at the organ, cellular, and sub-cellular levels. In this review, we also describe how technology can be used to reduce dendrimer toxicity, by changing their size and surface functionalization, how dendrimers can be combined with other materials to generate a composite formulation, and how dendrimers can be used for the diagnosis of disease. Finally, we discuss future challenges, developments, and research directions in developing biocompatible and safe dendrimers for medical purposes.
Nano silver is one of the most widely used engineering nanomaterials with antimicrobial activity against bacteria, fungi, and viruses. However, the widespread application of nano silver preparations in daily life raises concerns about public health. Although several review articles have described the toxicity of nano silver to specific major organs, an updated comprehensive review that clearly and systematically outlines the harmful effects of nano silver is lacking. This review begins with the routes of exposure to nano silver and its distribution in vivo. The toxic reactions are then discussed on three levels, from the organ to the cellular and subcellular levels. This review also provides new insights on adjusting the toxicity of nano silver by changing their size and surface functionalization and their combination with other materials to form a composite formulation. Finally, future development, challenges, and research directions are discussed.
Combination therapy has gained a lot of attention thanks to its superior activity against cancer. In the present study, we report a cRGDtargeted liposomal preparation for co-delivery of programmed cell death ligand 1 (PD-L1) small interfering RNA (siRNA) and anemoside B4 (AB4)AB4/siP-c-Land evaluate its anticancer efficiency in mouse models of LLC and 4T1 tumors. AB4/siP-c-L showed a particle size of (180.7 ± 7.3) nm and a ζ-potential of (32.8 ± 1.5) mV, with high drug encapsulation, pH-sensitive release properties, and good stability in serum. AB4/siP-c-L demonstrated prolonged blood circulation and increased tumor accumulation. Elevated cellular uptake was dependent on the targeting ligand cRGD. This combination induced significant tumor inhibition in LLC xenograft tumor-bearing mice by downregulating PD-L1 protein expression and modulating the immunosuppressive microenvironment. Liposomes favored the antitumor T-cell response with long-term memory, without obvious toxicity. A similar tumor growth inhibition was also demonstrated in the 4T1 tumor model. In summary, our results indicate that cRGD-modified and AB4and PD-L1 siRNA-coloaded liposomes have potential as an antitumor preparation, and this approach may lay a foundation for the development of a new targeted drug delivery system.
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