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The treatment of brain tumors remains a challenge due to the limited accumulation of drugs and nanoparticles. Here, we triggered the aggregation of gold nanoparticles (AuNPs) using legumain to enhance the retention of chemotherapeutics in brain tumors. This nanoplatform, AuNPs-A&C, is comprised of Ala-Ala-Asn-Cys-Lys modified AuNPs (AuNPs-AK) and 2-cyano-6-aminobenzothiazole modified AuNPs (AuNPs-CABT). AuNPs-AK could be hydrolyzed to expose the 1,2-thiolamino groups on AuNPs-AK in the presence of legumain, which occurs by a click cycloaddition with the contiguous cyano group on AuNPs-CABT, resulting in formation of AuNPs aggregates. This strategy led to an enhanced retention of the AuNPs in glioma cells both in vitro and in vivo due to the blocking of nanoparticle exocytosis and minimizing nanoparticle backflow to the bloodstream. After conjugation of doxorubicin (DOX) via a pH-sensitive linker to AuNPs-A&C, the efficiency for treating glioma was improved. The median survival time for the DOX-linked AuNPs-A&C increased to 288% in comparison to the saline group. We further show the use of the AuNPs-A&C for optical imaging applications. In conclusion, we provide a strategy to increase nanoparticle tumor accumulation with the potential to improve therapeutic outcome.

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Tissue engineering is a promising strategy to treat tissue and organ loss or damage caused by injury or disease. During the past two decades, mesenchymal stem cells (MSCs) have attracted a tremendous amount of interest in tissue engineering due to their multipotency and self-renewal ability. MSCs are also the most multipotent stem cells in the human adult body. However, the application of MSCs in tissue engineering is relatively limited because it is difficult to guide their differentiation toward a specific cell lineage by using traditional biochemical factors. Besides biochemical factors, the differentiation of MSCs also influenced by biophysical cues. To this end, much effort has been devoted to directing the cell lineage decisions of MSCs through adjusting the biophysical properties of biomaterials. The surface topography of the biomaterial-based scaffold can modulate the proliferation and differentiation of MSCs. Presently, the development of micro- and nano-fabrication techniques has made it possible to control the surface topography of the scaffold precisely. In this review, we highlight and discuss how the main topographical features (i.e., roughness, patterns, and porosity) are an efficient approach to control the fate of MSCs and the application of topography in tissue engineering.