Dual loading miR-218 mimics and Temozolomide using AuCOOH@FA-CS drug delivery system: promising targeted anti-tumor drug delivery system with sequential release functions

Supplementary figures. (DOCX 524 kb

GNPs-CS/KGM as hemostatic first aid wound dressing with antibiotic effect: in vitro and in vivo study.

Ideal wound dressing materials should create a good healing environment, with immediate hemostatic effects and antimicrobial activity. In this study, chitosan/konjac glucomannan (CS/KGM) films embedded with gentamicin-loaded poly(dex-GMA/AAc) nanoparticles (giving GNP-CS/KGM films) were prepared as novel wound dressings. The results revealed that the modified CS/KGM films could be used as effective wound dressings and had significant hemostatic effects. With their microporous structure, the films could effectively absorb water from blood and trap blood cells. The gentamicinloaded poly(dex-GMA/AAc) nanoparticles (GNPs) also further promoted blood clotting, with their favorable water uptake capacity. Thus, the GNP-CS/KGM films had wound healing and synergistic effects that helped to stop bleeding from injuries, and also showed good antibiotic abilities by addition of gentamicin to the NPs. These GNPCS/KGM films can be considered as promising novel biodegradable and biocompatible wound dressings with hemostatic capabilities and antibiotic effects for treatment of external bleeding injuries

Improved Synthesis of a Novel Biodegradable Tunable Micellar Polymer Based on Partially Hydrogenated Poly(β-malic Acid-co-benzyl Malate)

Poly(benzyl malate) (PBM), together with its derivatives, have been studied as nanocarriers for biomedical applications due to their superior biocompatibility and biodegradability. The acquisition of PBM is primarily from chemical routes, which could offer polymer-controlled molecular weight and a unique controllable morphology. Nowadays, the frequently used synthesis from L-aspartic acid gives an overall yield of 4.5%. In this work, a novel synthesis route with malic acid as the initiator was successfully designed and optimized, increasing the reaction yield up to 31.2%. Furthermore, a crystalline form of PBM (PBM-2) that polymerized from high optical purity benzyl-β-malolactonate (MLABn) was discovered during the optimization process. X-ray diffraction (XRD) patterns revealed that the crystalline PBM-2 had obvious diffraction peaks, demonstrating that its internal atoms were arranged in a more orderly manner and were different from the amorphous PBM-1 prepared from the racemic MLABn. The differential scanning calorimetry (DSC) curves and thermogravimetric curves elucidated the diverse thermal behaviors between PBM-1 and PBM-2. The degradation curves and scanning electron microscopy (SEM) images further demonstrated the biodegradability of PBM, which have different crystal structures. The hardness of PBM-2 implied the potential application in bone regeneration, while it resulted in the reduction of solubility when compared with PBM-1, which made it difficult to be dissolved and hydrogenated. The solution was therefore heated up to 75 °C to achieve benzyl deprotection, and a series of partially hydrogenated PBM was sequent prepared. Their optimal hydrogenation rates were screened to determine the optimal conditions for the formation of micelles suitable for drug-carrier applications. In summary, the synthesis route from malic acid facilitated the production of PBM for a shorter time and with a higher yield. The biodegradability, biosafety, mechanical properties, and adjustable hydrogenation widen the application of PBM with tunable properties as drug carriers

Targeting and sensitizing MDR cancer by an MMP2 and pH dual-responsive ZnO-based nanomedicine

Abstract Zinc oxide nanoparticles (ZnO NPs) have been known as a therapeutic agent and drug delivery system for treating various diseases, including infectious diseases and cancer. However, due to the low biocompatibility, short in vivo half-life, and potential toxicity, the previous studies on ZnO NPs were mainly focused on their in vitro applications. The effective and safe ZnO NP-based systems which can be used for in vivo drug delivery have been rarely reported. In this study, we developed a novel dual-responsive hybrid ZnO NP (ZnO/DPPG/PEG-pp-PE) consisting of the ZnO NPs, phospholipid (DPPG), and enzyme-sensitive amphiphilic polymer (PEG-pp-PE), which could respond to both tumoral matrix metalloproteinase 2 (MMP2) and intracellular acidic pH, for tumor-targeted drug delivery and multidrug resistant (MDR) cancer treatment. The dual-responsive ZnO/DPPG/PEG-pp-PE could easily load the model drug, doxorubicin (DOX), and showed excellent physicochemical properties, stability, and MMP2 and pH dual sensitivity. The ZnO/DPPG/PEG-pp-PE/DOX showed the MMP2-dependent cellular uptake, enhanced cell penetration, and improved anticancer activity in the MDR cancer cells and their spheroids. In the MDR tumor-bearing mice, the ZnO/DPPG/PEG-pp-PE/DOX improved the biocompatibility, tumor targetability, and anticancer activity of DOX and ZnO without significant toxicity compared to the free DOX, ZnO/DOX, and nonsensitive ZnO NPs. The data suggested that the dual-sensitive ZnO-based nanomedicine could be a promising delivery system for targeted drug delivery and therapy against the MDR cancer

Preparation of Two Types of Polymeric Micelles Based on Poly(β-L-Malic Acid) for Antitumor Drug Delivery - Fig 3

<p>¹HNMR spectra of PMLA(A), PMLABz(B), P1(C) and P2(D) (DMSO-d6, 500 MHz).</p

¹H-NMR spectra of DEX-GMA.

<p>(a), Morphology of nanoparticles observed by TEM (b) (A: blank nanoparticles, B: drug loaded nanoparticles), Particle size distribution from DLS analysis (c) (A: blank nanoparticles, B: drug loaded nanoparticles).</p

IC₅₀ values for CPT and micelles in FR-positive Hela cells.

<p>(Mean ± SD, n = 3).</p

Two types of self-assembled PMs based on CPT-conjugated PMLA.

<p>Two types of self-assembled PMs based on CPT-conjugated PMLA.</p

Cellular uptake of FITC-labeled P1 micelles and FP1 micelles in FR-positive Hela.

<p>Cells were incubated with FITC-labeled P1 micelles for 15 min (A), 1 h (B) or 4 h (C) at 37°C. Cells were incubated with FITC-labeled FP1 micelles for 15 min (D), 1 h (E) or 4 h(F) at 37°C. Then the Cellular uptake was observed by confocal laser scanning fluorescence microscopy.</p

In vitro cumulative release profile of Gentamicin.

<p>From Poly (DEX-GMA/AAc) nanoparticles (A) and GNPs-CS/KGM (B).</p