Co-encapsulation of curcumin and doxorubicin in albumin nanoparticles blocks the adaptive treatment tolerance of cancer cells

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BM-MSCs alleviate diabetic nephropathy in male rats by regulating ER stress, oxidative stress, inflammation, and apoptotic pathways

Introduction: Diabetic nephropathy (DN), a chronic kidney disease, is a major cause of end-stage kidney disease worldwide. Mesenchymal stem cells (MSCs) have become a promising option to mitigate several diabetic complications.Methods: In this study, we evaluated the therapeutic potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) in a rat model of STZ-induced DN. After the confirmation of diabetes, rats were treated with BM-MSCs and sacrificed at week 12 after treatment.Results: Our results showed that STZ-induced DN rats had extensive histopathological changes, significant upregulation in mRNA expression of renal apoptotic markers, ER stress markers, inflammatory markers, fibronectin, and intermediate filament proteins, and reduction of positive immunostaining of PCNA and elevated P53 in kidney tissue compared to the control group. BM-MSC therapy significantly improved renal histopathological changes, reduced renal apoptosis, ER stress, inflammation, and intermediate filament proteins, as well as increased positive immunostaining of PCNA and reduced P53 in renal tissue compared to the STZ-induced DN group.Conclusion: In conclusion, our study indicates that BM-MSCs may have therapeutic potential for the treatment of DN and provide important insights into their potential use as a novel therapeutic approach for DN

P‑gp Inhibition and Mitochondrial Impairment by Dual-Functional Nanostructure Based on Vitamin E Derivatives To Overcome Multidrug Resistance

Vitamin E derivatives possess many essential features for drug-delivery applications, such as biocompatibility, stability, improvement of water solubility of hydrophobic compounds, anticancer activity, and the ability to overcome multidrug resistance (MDR). Herein, vitamin E derivatives are used to overcome MDR through a combined P-glycoprotein (P-gp) inhibition and mitochondrial impairment strategy. A novel nanomicellar drug-delivery system as a carrier for doxorubicin (DOX) was developed, in which d-α-tocopheryl polyethylene glycol 1000 succinate was used as a P-gp inhibitor, α-tocopheryl succinate was introduced as a mitochondrial disrupting agent, and d-α-tocopheryl polyethylene glycol 2000 succinate was used as the main building block of micelles. The optimal ratio between the components of the nanocarrier was determined. The resultant DOX-loaded mixed micelles exhibited a suitable size of 52.08 nm, high drug-loading encapsulation efficiency (>98%), high stability, and pH-dependent drug release. In vitro experiments demonstrated a significantly increased cytotoxic activity of DOX-loaded mixed micelles against resistant MCF-7/Adr cells (45-fold higher than DOX after 48 h of treatment). In vivo studies revealed superior antitumor efficiency with less cardio- and hepatotoxicities of DOX-loaded micelles compared with that of free DOX. These results highlight that the developed DOX-loaded mixed micelles have a promising potential to overcome MDR in chemotherapy for clinical usage

Near-Infrared Emission CuInS/ZnS Quantum Dots: All-in-One Theranostic Nanomedicines with Intrinsic Fluorescence/Photoacoustic Imaging for Tumor Phototherapy

Many theranostic nanomedicines (NMs) have been fabricated by packaging imaging and therapeutic moieties together. However, concerns about their potential architecture instability and pharmacokinetic complexity remain major obstacles to their clinical translation. Herein, we demonstrated the use of CuInS/ZnS quantum dots (ZCIS QDs) as “all-in-one” theranostic nanomedicines that possess intrinsic imaging and therapeutic capabilities within a well-defined nanostructure. ZCIS QDs were exploited for multispectral optical tomography (MSOT) imaging and synergistic PTT/PDT therapy. Due to the intrinsic fluorescence/MSOT imaging ability of the ZCIS QDs, their size-dependent distribution profiles were successfully visualized at tumor sites <i>in vivo</i>. Our results showed that the smaller nanomedicines (ZCIS NMs-25) have longer tumor retention times, higher tumor uptake, and deeper tumor penetration than the larger nanomedicines (ZCIS NMs-80). The ability of ZCIS QDs to mediate photoinduced tumor ablation was also explored. Our results verified that under a single 660 nm laser irradiation, the ZCIS NMs had simultaneous inherent photothermal and photodynamic effects, resulting in high therapy efficacy against tumors. In summary, the ZCIS QDs as “all-in-one” versatile nanomedicines allow high therapeutic efficacy as well as noninvasively monitoring tumor site localization profiles by imaging techniques and thus hold great potential as precision theranostic nanomedicines