Cancer nanomedicines rely on the enhanced permeability and retention (EPR) effect for efficient target site accumulation. The EPR effect, however, is highly heterogeneous among different tumor types and cancer patients and its extent is expected to dynamically change during the course of nanochemotherapy. Here the authors set out to longitudinally study the dynamics of the EPR effect upon single-and double-dose nanotherapy with fluorophore-labeled and paclitaxel-loaded polymeric micelles. Using computed tomography-fluorescence molecular tomography imaging, it is shown that the extent of nanomedicine tumor accumulation is predictive for therapy outcome. It is also shown that the interindividual heterogeneity in EPR-based tumor accumulation significantly increases during treatment, especially for more efficient double-dose nanotaxane therapy. Furthermore, for double-dose micelle therapy, tumor accumulation significantly increased over time, from 7% injected dose per gram (ID g -1 ) upon the first administration to 15% ID g -1 upon the fifth administration, contributing to more efficient inhibition of tumor growth. These findings shed light on the dynamics of the EPR effect during nanomedicine treatment and they exemplify the importance of using imaging in nanomedicine treatment prediction and clinical translation.

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Purpose. Sepsis originates from the host inflammatory response, especially to bacterial infections, and is considered one of the main causes of death in intensive care units. Various agents have been developed to inhibit mediators of the inflammatory response; one prospective agent is β-sitosterol (βS), a phytosterol with a structure similar to cholesterol. This study is aimed at evaluating the effects of βS on the biomarkers of inflammation and liver function in cecal ligation and puncture- (CLP-) induced septic rats. Methods. Thirty male Wistar rats were divided equally into six groups as follows: sham, CLP, CLP+dexamethasone (DX, 0.2 mg/kg), CLP+βS (1 mg/kg), CLP+imipenem (IMI, 20 mg/kg), and CLP+IMI (20 mg/kg)+βS (1 mg/kg). Serum levels of IL-1β, IL-6, IL-10, AST, ALT, and liver glutathione (GSH) were assessed by ELISA. Liver expression levels of TNF-α and NF-κBi mRNAs were evaluated by RT-qPCR. Results. Serum concentrations of IL-1β, IL-6, IL-10, ALT, and AST and mRNA levels of TNF-α and NF-κBi were all significantly higher in septic rats than in normal rats ( p < 0.05 ). Liver GSH content was markedly lower in the CLP group than that in the sham group. βS-treated rats had remarkably lower levels of IL-1β, IL-6, IL-10, TNF-α, NF-κBi, AST, and ALT (51.79%, 62.63%, 41.46%, 54.35%, 94.37%, 95.30%, 34.87%, and 46.53% lower, respectively) and greater liver GSH content (35.71% greater) compared to the CLP group ( p < 0.05 ). Conclusion. βS may play a protective role in the septic process by mitigating inflammation. This effect is at least partly mediated by inhibition of the NF-κB signaling pathway. Thus, βS can be considered as a supplementary treatment in septic patients.

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Graphene quantum dots (GQDs) are known as emerging sub‐10 nm nanoparticles (NPs), which are in fact few‐layered pieces of graphene, capable of emitting blue fluorescence, when exposed to 360 nm UV light. Understanding the details of the interaction between GQDs and lipase can serve as a critical step for improving the biological outcome of GQD‐derived drug‐delivery and diagnosis systems. The interaction occurs in the form of surface adsorption, which can subsequently influence the physicochemical properties of both the NP and the protein. Hence, a systematic approach was taken here to optimize the GQDs' synthesis conditions in order to achieve the highest possible quantum yield (QY). Furthermore, to understands the influence of the interaction of GQDs and lipase, on both the activity of lipase and the emission intensity of GQDs, various incubation conditions were tested to achieve optimized conditions over central composite design algorithm by Design‐Expert®, using response surface methodology. The results show that the GQDs fabricated by thermal decomposition of citric acid at 160°C, with a heating duration of 55 min, obtain almost three times higher QY than the highest values reported previously. The best enzymatic activity after the formation of the hard corona, as well as the highest fluorescent emission, were achieved at GQD‐to‐enzyme ratios within the rage of 23–25%, at temperatures between 41 and 42°C, for 6–8 min. In the aforementioned condition, the enzyme retains 91–95% of its activity and the NP preserves about 80–82% of its fluorescence intensity after incubation.

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Polymeric micelles are among the most extensively used drug delivery systems. Key properties of micelles, such as size, size distribution, drug loading, and drug release kinetics, are crucial for proper therapeutic performance. Whether polymers from more controlled polymerization methods produce micelles with more favorable properties remains elusive. To address this question, we synthesized methoxy poly(ethylene glycol)-b-(N-(2-benzoyloxypropyl)methacrylamide) (mPEG-b-p(HPMAm-Bz)) block copolymers of three different comparable molecular weights (∼9, 13, and 20 kDa), via both conventional free radical (FR) and reversible addition–fragmentation chain transfer (RAFT) polymerization. The polymers were subsequently employed to prepare empty and paclitaxel-loaded micelles. While FR polymers had relatively high dispersities (Đ ∼ 1.5–1.7) compared to their RAFT counterparts (Đ ∼ 1.1–1.3), they formed micelles with similar pharmaceutical properties (e.g., size, size distribution, critical micelle concentration, cytotoxicity, and drug loading and retention). Our findings suggest that pharmaceutical properties of mPEG-b-p(HPMAm-Bz) micelles do not depend on the synthesis route of their constituent polymers.