Developing biomimetic nanoparticles without loss of the integrity of proteins remains a major challenge in cancer chemotherapy. Here, we develop a biocompatible tumor-cell-exocytosed exosome-biomimetic porous silicon nanoparticles (PSiNPs) as drug carrier for targeted cancer chemotherapy. Exosome-sheathed doxorubicin-loaded PSiNPs (DOX@E-PSiNPs), generated by exocytosis of the endocytosed DOX-loaded PSiNPs from tumor cells, exhibit enhanced tumor accumulation, extravasation from blood vessels and penetration into deep tumor parenchyma following intravenous administration. In addition, DOX@E-PSiNPs, regardless of their origin, possess significant cellular uptake and cytotoxicity in both bulk cancer cells and cancer stem cells (CSCs). These properties endow DOX@E-PSiNPs with great in vivo enrichment in total tumor cells and side population cells with features of CSCs, resulting in anticancer activity and CSCs reduction in subcutaneous, orthotopic and metastatic tumor models. These results provide a proof-of-concept for the use of exosome-biomimetic nanoparticles exocytosed from tumor cells as a promising drug carrier for efficient cancer chemotherapy.
In this focus article, we provide a scrutinizing analysis of transmission electron microscopy and dynamic light scattering as the two common methods to study the sizes of nanoparticles with focus on the application in pharmaceutics and drug delivery.
Bone regenerative engineering provides a great platform for bone tissue regeneration covering cells, growth factors and other dynamic forces for fabricating scaffolds. Diversified biomaterials and their fabrication methods have emerged for fabricating patient specific bioactive scaffolds with controlled microstructures for bridging complex bone defects. The goal of this review is to summarize the points of scaffold design as well as applications for bone regeneration based on both electrospinning and 3D bioprinting. It first briefly introduces biological characteristics of bone regeneration and summarizes the applications of different types of material and the considerations for bone regeneration including polymers, ceramics, metals and composites. We then discuss electrospinning nanofibrous scaffold applied for the bone regenerative engineering with various properties, components and structures. Meanwhile, diverse design in the 3D bioprinting scaffolds for osteogenesis especially in the role of drug and bioactive factors delivery are assembled. Finally, we discuss challenges and future prospects in the development of electrospinning and 3D bioprinting for osteogenesis and prominent strategies and directions in future.
1 September 2021 in Advanced Drug Delivery Reviews
CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats-associated protein 9) is a potent technology for gene-editing. Owing to its high specificity and efficiency, CRISPR/Cas9 is extensity used for human diseases treatment, especially for cancer, which involves multiple genetic alterations. Different concepts of cancer treatment by CRISPR/Cas9 are established. However, significant challenges remain for its clinical applications. The greatest challenge for CRISPR/Cas9 therapy is how to safely and efficiently deliver it to target sites in vivo. Nanotechnology has greatly contributed to cancer drug delivery. Here, we present the action mechanisms of CRISPR/Cas9, its application in cancer therapy and especially focus on the nanotechnology-based delivery of CRISPR/Cas9 for cancer gene editing and immunotherapy to pave the way for its clinical translation. We detail the difficult barriers for CRISIR/Cas9 delivery in vivo and discuss the relative solutions for encapsulation, target delivery, controlled release, cellular internalization, and endosomal escape.