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Surgical resection remains the preferred approach for some patients with glioblastoma (GBM), and eradication of the residual tumour niche after surgical resection is very helpful for prolonging patient survival. However, complete surgical resection of invasive GBM is difficult because of its ambiguous boundary. Herein, a novel targeting material, c(RGDyk)-poloxamer-188, was synthesized by modifying carboxyl-terminated poloxamer-188 with a glioma-targeting cyclopeptide, c(RGDyk). Quantum dots (QDs) as fluorescent probe were encapsulated into the self-assembled c(RGDyk)-poloxamer-188 polymer nanoparticles (NPs) to construct glioma-targeted QDs-c(RGDyk)NP for imaging-guided surgical resection of GBM. QDs-c(RGDyk)NP exhibited a moderate hydrodynamic diameter of 212.4 nm, a negative zeta potential of –10.1 mV and good stability. QDs-c(RGDyk)NP exhibited significantly lower toxicity against PC12 and C6 cells and HUVECs than free QDs. Moreover, in vitro cellular uptake experiments demonstrated that QDs-c(RGDyk)NP specifically targeted C6 cells, making them display strong fluorescence. Combined with ultrasound-targeted microbubble destruction (UTMD), QDs-c(RGDyk)NP specifically accumulated in glioma tissue in orthotropic tumour rats after intravenous administration, evidenced by ex vivo NIR fluorescence imaging of bulk brain and glioma tissue sections. Furthermore, fluorescence imaging with QDs-c(RGDyk)NP guided accurate surgical resection of glioma. Finally, the safety of QDs-c(RGDyk)NP was verified using pathological HE staining. In conclusion, QDs-c(RGDyk)NP may be a potential imaging probe for imaging-guided surgery.

Photodynamic therapy (PDT) has recently emerged as a promising, targeted treatment modality for glioblastoma (GBM) which is the most vicious type of brain tumor. Successful GBM-PDT hinges upon light activation of a photosensitizer accumulated in the tumor. However, inadequate tumor accumulation of photosensitizer severely limits the success of PDT of GBM. To tackle this difficulty, we herein propose a drug delivery strategy of "platelets with photo-controlled release property". This strategy exploits platelets as carriers to deliver a photosensitizer which, in the current study, is a nano-composite (BNPD-Ce6) comprised of chlorine e6 (Ce6) loaded to boron nitride nanoparticles with a surface coating of polyglycerol and doxorubicin. To demonstrate the working mechanism and therapeutic advantage of this strategy, we loaded mouse platelets with BNPD-Ce6 to yield the nano-device BNPD-Ce6@Plt. In vitro experiments showed BNPD-Ce6@Plt to have a high loading capacity and efficiency. Laser irradiation (LI) at a wavelength of 808 nm induced ROS generation in BNPD-Ce6@Plt which displayed rapid activation, aggregation, and speedy discharge of BNPD-Ce6 into co-cultured GL261 mouse GBM cells which in turn, after LI, exhibited marked ROS generation, DNA damage, reduced viability, and cell death. In vivo animal experiments, mice that were intravenously injected with BNPD-Ce6@Plt exhibited rapid and extensive BNPD-Ce6 accumulation in both subcutaneous and intra-brain GL261 tumors shortly after LI of the tumors and the tumors displayed massive tissue necrosis after LI for a second time. Finally, a PDT regimen of two intravenous BNPD-Ce6@Plt injections each followed by multiple times of extracranial LI at the tumor site significantly inhibited the growth of intra-brain GL261 tumors and markedly increased the survival of the host animals. No apparent tissue damage was found in vital organs. Our findings make a compelling case for the notion that platelets are efficient carriers that can photo-controllably deliver nano-photosensitizers to achieve highly targeted and efficacious PDT of GBM. This work presents a novel approach to GBM-PDT with great translational potential.

Although silica nanoparticles (SiNPs) are produced in large numbers for industrial manufacturing and engineering applications, the effect of SiNPs on biotransformation in the environment is still not clear. In the current study, the effect of SiNPs in enhancing denitrification was investigated, and its mechanism was explored from the perspectives of electron transfer, microbial metabolism and bacterial community structure for the first time. Batch experiments showed that a concentration of SiNPs ranging from 0.05 to 5 g/L enhanced the bioreduction of nitrate. The mechanism study showed that SiNPs accelerated the extracellular electron transfer in the denitrification process due to their electron donating capacity, bonding action, and the secretion of more electron shuttles. During the denitrification process, SiNPs promoted metabolic activity, which mainly consists of promoting enzyme activities and electron transport system activity; these metabolic activity assays were positively correlated with SiNPs according to the structural equation modeling analysis. Moreover, SiNPs affected the composition of the microbial community, including denitrifying functional bacteria, silicon-activating bacteria and electron transfer active bacteria exhibiting a synergistic symbiosis. In addition, it was shown, by investigating two functional group-modified SiNPs, that the carboxyl modified SiNPs had the potential to be applied in nitrogen removal due to their performance and non-toxicity. This study presented a better insight into the role of SiNPs in biological transformation.

Atherosclerosis, which is triggered by endothelial damage, progressive local inflammation and excessive lipid accumulation, is one of the most common cardiovascular diseases in recent years. Drug delivery systems have shown great potential for the accurate diagnosis and effective treatment of early atherosclerosis, but are accompanied by disadvantages such as poor stability, lack of active targeting and non-specific recognition capabilities, which still need to be further developed. In our work, a multifunctional nanoparticle (LFP/PCDPD) with reactive oxygen species (ROS) responsive drug release, lipid removal, and lipid-specific AIE fluorescence imaging was constructed. Cyclodextrin structure with lipid removal function and PMEMA blocks with ROS-response-mediated hydrophobic to hydrophilic conversion were simultaneously introduced into the structure of LFP/PCDPD to load the anti-inflammatory drug prednisolone (Pred) and lipid-specific AIEgen (LFP). The active targeting function of LFP/PCDPD was conferred by the high affinity of dextran to the vascular adhesion molecule-1 (VCAM-1) and CD44 receptor on the surface of broken endothelial cells. After intravenous injection into ApoE

Atherosclerosis is one of the leading causes of cardiovascular diseases and is triggered by endothelial damage, local lipid cumulation, and inflammation. Despite the conventional medication treatment, nanosized drug carriers have become promising candidates for efficient drug delivery with lower side effects. However, the development of problems in nanocarriers such as drug leakage, accumulating efficiency, and accurate drug release, as well as the specific recognition of atherosclerotic plaques, still needs to be checked. In this study, a lipid-specific fluorophore (LFP) has been designed, which is further packaged with a reactive oxygen species (ROS)-responsive prednisolone (Pred) prodrug copolymer [PMPC-P(MEMA-co-PDMA)] to self-assemble into LFP@PMMP micelles. LFP@PMMP can be further coated with red blood cell (RBC) membrane to obtain surface-biomimetic nanoparticles (RBC/LFP@PMMP), demonstrating prolonged circulation, minimal drug leakage, and better accumulation at the plaques. With ROS responsiveness, RBC/LFP@PMMP can be interrupted at inflammatory atherosclerotic tissue with overexpressed ROS, followed by the dissociation of Pred from the polymer backbone and the release of LFP to combine with the rich lipid in the plaques. An accurate anti-inflammation and lipid-specific fluorescent imaging of atherosclerotic lesions was performed and further proven on ApoE-/- mice; this holds prospective potential for atherosclerosis theranostics.