Cancer cell membrane-camouflaged paclitaxel/PLGA nanoparticles for targeted therapy against lung cancer.

Paclitaxel (PTX) is a first-line drug for the treatment of lung cancer, but its targeting and therapeutic effect are unsatisfactory. Herein, lung cancer cell (A549) membrane biomimetic PTX-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (AM@PTX-NPs) were constructed to eliminate the shortcomings of PTX. The AM@PTX-NPs were successfully prepared with a high drug loading efficiency (10.90±0.06 %). Moreover, transmission electron microscopy, SDS-PAGE, and western blotting proved that AM@PTX-NPs were spherical nanoparticles camouflaged by the A549 cell membrane. Both in vitro and in vivo assays revealed that the AM@PTX-NPs displayed outstanding targeting capacity due to A549 membrane modification. The cytotoxicity experiment showed that the developed biomimetic formulation was able to effectively reduce the proliferation of A549 cells. Moreover, AM@PTX-NPs exhibited a significant tumor growth inhibition rate (73.00 %) with good safety in the tumor-bearing mice, which was higher than that of the PTX-NPs without A549 membrane coating (37.39 %). Overall, the constructed bioinspired vector could provide a novel platform for the PTX delivery and demonstrated a promising strategy for the targeted cancer treatment.

Biomimetic platelet-like nanoparticles enhance targeted hepatocellular carcinoma therapy.

Curcumin (CUR) is a promising natural product for hepatocellular carcinoma (HCC) therapy. However, its clinical application has been limited by some issues such as rapid clearance and inadequate tumor accumulation. To address these drawbacks, we developed platelet membrane-coated CUR-loaded PLGA nanoparticles (PCPNPs). In this work, due to the bioinspired strategy, the PCPNPs exhibited immune evasion, prolonged circulation, and improved accumulation at tumor sites compared to the traditional CUR formulation. The superior tumor targeting of PCPNPs was likely due to the interactions between platelet P-selectin and tumoral CD44. Furthermore, both in vitro and in vivo assays revealed that the PCPNPs showed outstanding anticancer efficacy without obvious toxicity. Therefore, PCPNPs represent a biosafe and promising anti-tumor strategy, overcoming the limitations associated with CUR. These findings not only contribute to the advancement of natural compound nano-formulation but also open new avenues for targeted cancer treatment.

Preparation, identification, and molecular docking of novel angiotensin-converting enzyme inhibitory peptides derived from rice-based distillers' spent cakes.

BACKGROUND: Rice-based distillers' spent cake (RDSC), a by-product of the Chinese liquor (Baijiu) industry, is a potential source of angiotensin-converting enzyme (ACE) inhibitory peptide. Since ACE plays a crucial role in controlling hypertension, inhibition of ACE has been widely emphasized. The ACE inhibitory active peptide derived from by-products of food has been recognized as a safer and cheaper inhibitor. RESULTS: Aimed to discover ACE-inhibiting active peptides in RDSC. Hydrolysis of RDSC by alcalase for 4 h followed by ultrafiltration yielded low-molecular-weight (< 3 kDa) fractions. Subsequently, a comprehensive method using a combination of liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS) and LC-Q-Exactive-MS to identify the novel short peptides (3-5 amino acids residues; n = 7) and medium-sized peptides (more than 6 amino acids residues; n = 6). In vitro activity assay showed that the peptides KPFFPGL, GFPRPLL, GPPGVF, and VGK exhibited the highest activity with inhibitory concentration of 50% (IC50) of 11.63, 12.34, 19.55, and 33.54 µmol L-1. Molecular docking reveal that the active and inactive sites (Glu123, Asp121, Arg522, and Lys118) play important roles in enhancing the ACE inhibitory activity of peptides. CONCLUSION: Here we report a comprehensive method that effectively extracted and identified the bioactive peptides from RDSC. Four highly active novel peptides may be the most promising candidates for functional foods against hypertension, provide significant information for enhancing value of rice-based distilled by-products. © 2024 Society of Chemical Industry.

Fabrication, Optimization, and Evaluation of Paclitaxel and Curcumin Coloaded PLGA Nanoparticles for Improved Antitumor Activity.

Codelivery of chemotherapeutic drugs in nanoparticles can enhance the therapeutic effects against tumors. However, their anticancer properties and physiochemical characteristics can be severely influenced by many formulation parameters during the preparation process. It is a complicated development phase to select the optimal parameters for preparation of nanoparticles based on the commonly used one single parameter method, which consumes a lot of money, time, and effort, and sometimes even fails. Therefore, the statistical analysis based on Box-Behnken design (BBD) has attracted much attention in bioengineering fields because it can illustrate the influence of parameters, build mathematical models, and predict the optimal combinational factors in a decreased number of experiments. In this study, we used a three-factor three-level BBD design to optimize the preparation of poly(lactic-co-glycolic acid) (PLGA) nanoparticles coloaded with two anticancer drugs curcumin and paclitaxel (PLGA-CUR-PTX nanoparticles). The surfactant concentration, polymer concentration, and oil-water ratio were selected as independent variables. An optimized model of the formulation for PLGA-CUR-PTX nanoparticles was validated. The optimal nanoparticles possessed a uniform spherical shape, with an average size of 99.94 nm, and the drug encapsulation efficiencies of CUR and PTX were 63.53 and 80.64%, respectively. The drug release from nanoparticles showed a biphasic release behavior, with a release mechanism via diffusion and fundamentally quasi-Fickian diffusion. The optimized nanoparticles demonstrated an enhanced cytotoxicity effect with lower IC50 values to 4T1 and MCF-7 breast cancer cell lines compared to free drugs. In summary, BBD optimization of CUR and PTX coloaded nanoparticles yielded a favorable drug carrier that holds potential as an alternative treatment for anticancer therapy.

Preparation and optimization of poly (lactic-co-glycolic acid) rod-shaped particles in nano size range for paclitaxel delivery.

Nanoparticle shape has been acknowledged as an important design parameter due to its influence on nanoparticle interaction with biological systems. However, there is lacking of simple and scalable preparation technique for drug loaded non-spherical polymeric nanoparticles for a long time, thus hindering the potential applications. Although our previous research has modified the traditional emulsion solvent evaporation technique by adding guest molecules to prepare non-spherical poly (lactic-co-glycolic acid) (PLGA) particles, it is difficult to obtain nano-sized rods with minor axis less than 200 nm, which may have great potential in cancer therapy. Herein, in present research, the two-step ESE method was used and optimized to prepare poly (lactic-co-glycolic acid) nanorods for paclitaxel delivery. Firstly, the single-factor experiment was used to screen the influence of multi-factors including type of guest molecules, concentration of guest molecules, emulsification method, surfactant concentration, oil volume, poly (lactic-co-glycolic acid) concentration on the size and shape to determine the range of variables; based on the above range, a multi-factor and multi-level orthogonal experiment was designed. The formula is evaluated by the rod fabrication yield and the aspect ratio of major axis to minor axis. The results showed that the yield of nanorods in the optimal formula was 99% and the aspect ratio was 5.35 ± 2.05 with the minor axis of 135.49 ± 72.66 nm, and major axis of 657.77 ± 307.63 nm. In addition, the anti-cancer drug paclitaxel was successfully encapsulated in PLGA nanorods by the same technique. Our results not only enrich the ESE technique for preparing small sized poly (lactic-co-glycolic acid) nanorods, but also envision the potential application of nanorods for targeted cancer therapy with the delivery of paclitaxel.