Cationic Polymer Research Articles

Engineered Bacteriophage-Polymer Nanoassemblies for Treatment of Wound Biofilm Infections.

The antibacterial efficacy and specificity of lytic bacteriophages (phages) make them promising therapeutics for treatment of multidrug-resistant bacterial infections. Restricted penetration of phages through the protective matrix of biofilms, however, may limit their efficacy against biofilm infections. Here, engineered polymers were used to generate noncovalent phage-polymer nanoassemblies (PPNs) that penetrate bacterial biofilms and kill resident bacteria. Phage K, active against multiple strains of Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), was assembled with cationic poly(oxanorbornene) polymers into PPNs. The PPNs retained phage infectivity, while demonstrating enhanced biofilm penetration and killing relative to free phages. PPNs achieved 3-log10 bacterial reduction (∼99.9%) against MRSA biofilms in vitro. PPNs were then incorporated into Poloxamer 407 (P407) hydrogels and applied onto in vivo wound biofilms, demonstrating controlled and sustained release. Hydrogel-incorporated PPNs were effective in a murine MRSA wound biofilm model, showing a 1.5-log10 reduction in bacterial load compared to a 0.5 log reduction with phage K in P407 hydrogel. Overall, this work showcases the therapeutic potential of phage K engineered with cationic polymers for treating wound biofilm infections.

Novel Electrospun Zwitterionic Nanofibers for Point‐Of‐Care Nucleic Acid Isolation Strategies Under Mild Conditions

AbstractNucleic acid (NA) testing at the point‐of‐care requires efficient NA extraction followed by post‐NA amplification to achieve necessary detection sensitivity. Nanofibers (NFs) are demonstrated to be an ideal solid surface in an NA extraction process but necessitate harsh conditions that interfere with the subsequent NA amplification process. It is demonstrated that novel, pH tunable, zwitterionic NFs composed of uncharged nylon doped with the weakly basic, cationic polyallylamine hydrochloride and the weakly acidic anionic polycarboxylic acid to address the issue. Unlike the other cationic polymers investigated, e.g. polybrene and polyaniline, these polymers allow efficient NA extraction in Tris‐ethylenediamine tetra‐acetic acid buffer under mild conditions (pH 4.5 containing 0.1% Tween 20 for adsorption, and pH 10 with 50 mM NaCl for elution). Adsorption and elution yields over 95% and 70%, respectively, are achieved. It also discovered a correlation between material morphologies and the NA extraction suggests that the combination of polymer chemistries and nanofiber morphologies facilitates efficient NA extraction at low concentrations (ng range) within a short time period (<10 min). Considering the simple protocols and instrument‐free operation the as‐developed NFs are highly attractive for use in sample‐to‐answer NA testing in point‐of‐care settings.

Synthesis and structural characterization of new chitosan-thiamine hydrochloride molecular complexes

Chitosan is one of the natural cationic polymers used for drug delivery due to its unique properties as an antimicrobial and antioxidant agent. In this work, three new molecular complexes were obtained by mechanically grinding a mixture of chitosan and thiamine hydrochloride in weight ratios of 4:1, 3:2, and 1:1, with a few drops of acetic acid and sodium citrate solutions. Complementary analyses, including X-ray powder diffraction, differential thermal analyses, thermogravimetric analyses, Fourier transform infrared spectroscopy, and CP/MAS 13C NMR, were performed to characterize the new molecular complexes. X-ray diffraction revealed the transformation of chitosan from a semi-crystalline to an amorphous state after mechanochemical grinding. Infrared spectroscopy showed changes in the vibrations of the functional groups CO, OH, and NH in the structure of the developed compounds, indicating the interconnection of the components. Solid-state nuclear magnetic resonance spectroscopy recorded shifts of the resonance lines present in the ball-milled samples, compared to the initial compounds, along with the appearance of new lines, supporting the formation of chitosan-thiamine hydrochloride complexes. Thermal analyses confirmed the successful development of new molecular complexes by the appearance of two new exothermic signals at lower temperatures than those observed for chitosan.

Cationic Amphiphilic Comb-Shaped Polymer Emulsifier for Fabricating Avermectin Nanoemulsion with Exceptional Leaf Behaviors and Multidimensional Controlled Release.

The development of intelligent multifunctional nanopesticides featuring enhanced foliage affinity and hierarchical target release is increasingly pivotal in modern agriculture. In this study, a novel cationic amphiphilic comb-shaped polymer, termed PEI-TA, was prepared via a one-step Michael addition between low-molecular-weight biodegradable polyethylenimine (PEI) and tetradecyl acrylate (TA), followed by neutralization with acetic acid. Using the emulsifier PEI-TA, a positively charged avermectin (AVM) nanoemulsion was prepared via a phase inversion emulsification process. Under optimal formulation, the obtained AVM nanoemulsion (defined as AVM@PEI-TA) demonstrated exceptional properties, including small size (as low as 67.6 nm), high encapsulation efficiency (up to 87.96%), and high stability toward shearing, storage, dilution, and UV irradiation. The emulsifier endowed AVM@PEI-TA with a pronounced thixotropy, so that the droplets exhibited no splash and bounce when they were sprayed on the cabbage leaf. Owing to the electrostatic attraction between the emulsifier and the leaf, AVM@PEI-TA showed improved leaf adhesion, better deposition, and higher washing resistance in contrast to both its negatively charged counterpart and AVM emulsifiable concentrate (AVM-EC). Compared to the large-sized particles, the small-sized particles of the AVM nanoemulsion more effectively traveled long distances through the vascular system of veins after entering the leaf apoplast. Moreover, the nanoparticles lost stability when exposed to multidimensional stimuli, including pH, temperature, esterase, and ursolic acid individually or simultaneously, thereby promoting the release of AVM. The release mechanisms were discussed for understanding the important role of the emulsifier in nanopesticides.

Perhalogenated Anions as Structure Directing Agents of Cationic Coordination Polymers

Perhalogenated Anions as Structure Directing Agents of Cationic Coordination Polymers

Scalable fabrication of hypercrosslinked imidazole cationic polymer membranes for the efficient removal of 99TcO4−/ReO4−

Developing efficient and low-cost materials and technologies for the radioactive pertechnetate anion (99TcO4−) removal from contaminated groundwater is highly desired but remains a challenge. Herein, hypercrosslinked imidazole cationic polymers (HIPs), HIPs-1 and HIPs-2, were prepared. Benefiting from high density imidazole cationic groups, HIPs-2 exhibited rapid removal kinetics (with ∼100 % removal efficiency within 30 s) and considerable adsorption capacity (632.5 mg/g) in perrhenate anion (ReO4−, nonradioactive surrogate of 99TcO4−) spiked aqueous solution. HIPs-2 also showed excellent capture for ReO4− in groundwater (with dynamic adsorption capacities of 136.4 mg/g in ReO4−-spiked groundwater). Theoretical calculation revealed the adsorption mechanism of ion exchange. Encouraged by the excellent adsorption properties, HIPs-2 were fabricated into membranes M-HIPs-2/PAN using electrospinning. Dynamic adsorption experiments showed that ∼0.0934 g M-HIPs-2/PAN could continuously purify 1110 mL of ∼5.66 ppm ReO4−-spiked tap water to 0 ppm, with dynamic adsorption capacity of 87.3 mg/g. And still the dynamic adsorption capacity was 32.4 mg/g in ReO4−-spiked groundwater. M-HIPs-2/PAN exhibited satisfactory cycling stability, removing more than 97.5 % of the ReO4− after six cycles. More importantly, M-HIPs-2/PAN, derived from inexpensive raw materials with simple synthesis process, provides an efficient and economical approach for the large-scale treatment of groundwater contaminated with 99TcO4−.

DPA-Zn enables targeting and bypassing endosomal trapping delivery of a genome-editing system into cancer cells via phosphatidylserine-mediated endocytic pathway

Conventionally, cationic polymers can deliver genome-editing macromolecules into target cells via endocytosis. However, these vectors have low targeting ability and highly undesirable endosome trapping, and hence, only a very small fraction of delivered molecules can enter the cytosol of target cells, while most of them are degraded in lysosomes. Up to date, both targeting and bypassing endosomal trapping delivery are still challenging. It is very intersting to find that dipicolylamine-zinc (DPA-Zn) structures on polyplex surfaces can enable polyplexes to directly transport genome editing molecules into the cytosol without severe endosomal trapping not via classical endocytic pathways but via a new phosphatidylserine-mediated endocytic pathway. Moreover, DPA-Zn can highly target tumors, which highly enhances gene editing efficiency. This method provides an innovative method for successful targeting and bypassing endosomal trapping delivery of different biomacromolecules into cancer cells, bypassing the major obstacle of endosomal trapping.

Cyano-functionalized porous hyper-crosslinked cationic polymers for efficient preconcentration and detection of phenolic endocrine disruptors in fresh water and fish

Sensitively analyzing phenolic endocrine-disrupting chemicals (EDCs) in environmental substrates and aquatic organisms provides a significant challenge. Here, we developed a novel porous hyper-crosslinked ionic polymer bearing cyano groups (CN-HIP) as adsorbent for the highly efficient solid phase extraction (SPE) of phenolic EDCs in water and fish. The CN-HIP gave an excellent adsorption capability for targeted EDCs over a wide pH range, and the adsorption capacity was superior to that of several common commercial SPE adsorbents. The coexistence of electrostatic forces, hydrogen bond, and π-π interactions was confirmed as the main adsorption mechanism. A sensitive quantitative method was established by coupling CN-HIP based SPE method with high-performance liquid chromatography for the simultaneously determining trace bisphenol A, bisphenol F, bisphenol B and 4-tert-butylphenol in fresh water and fish. The method afforded lower detection limits (S/N = 3) (at 0.03–0.10 ng mL−1 for water and 0.8–4.0 ng g−1 for fish), high accuracy (the recovery of spiked sample at 88.0%–112 %) and high precision (the relative standard deviation < 8.5 %). This work provides a feasible method for detecting phenolic EDCs, and also opens a new perspective in developing functionalized cationic adsorbent.

Real-time detection of Tau-381 protein using liquid crystal-based sensors for Alzheimer's disease diagnosis

Tau is a protein found in the central nervous system (CNS) and is involved in stabilizing microtubules in axons. Given the link between Tau levels in the body and Alzheimer's disease (AD), there is a demand for straightforward and precise strategies to detect Tau in body fluids. In this study, we report liquid crystal (LC)-based sensors for the real-time detection of Tau protein, a well-known AD biomarker. The sensor uses a detection method based on the orientation change of the LC because of the competitive biomolecular interaction between Tau and Tau aptamers with the cationic polymer poly-L-lysine (PLL). Tau and its aptamers form stable complexes through electrostatic interactions. Owing to the consumption of the aptamer, the positively charged PLL fails to interact with the aptamer but binds to the negatively charged 1.2-dioleoyl-sn-glycero-3-phospho-(1′-rac-glycerol) sodium salt (DOPG). The PLL and DOPG complex alters the orientation of the LC to ensure a planar anchoring of the 4-cyano-4′-pentylbiphenyl (5CB)/aqueous interface; this anchoring intensifies with increasing Tau concentration, thus enabling the observation of a bright optical image. Our LC-based sensor demonstrated a low detection limit of 2.77 pg/mL in phosphate buffered saline (PBS) and 10.86 pg/mL and 19.31 pg/mL in human serum and plasma, respectively. Moreover, it is anticipated to be suitable for point-of-care diagnosis of AD because it does not require specialized analytical equipment and only requires microliters of sample.

New Antibacterial and Antioxidant Chitin Derivatives: Ultrasonic Preparation and Biological Effects.

This work focuses on the first use of ultrasonic phenol-ene coupling as a polymer analogous transformation. The ultrasonic reaction was introduced into chitin chemistry, resulting in the fast and convenient preparation of new water-soluble cationic chitin derivatives. Since water-soluble derivatives of fully deacetylated chitin are poorly described in the literature, the synthesis of each new type of these derivatives is a significant event in polysaccharide chemistry. Polycations, or cationic polymers, are of particular interest as antibacterial agents. Consequently, the resulting polymers were tested for their antibacterial activity and toxicity. We found that the highly substituted polymer of medium molecular weight exhibited the most pronounced in vitro antibacterial effect. We prepared nanoparticles using the ionic gelation technique. The most effective in vitro antibacterial chitin-based systems were tested in vivo in rats. These tests demonstrated outstanding antibacterial effects combined with an absence of toxicity. Additionally, we found that the resulting polymers, unlike their nanoparticle counterparts, also exhibited strong antioxidant effects. In summary, we demonstrated the effectiveness of ultrasound in polymer chemistry and highlighted the importance of the sonochemical approach in the chemical modification of polysaccharides. This approach enables the synthesis of derivatives with improved physicochemical and biological properties.

SDSSD peptide modified polyvinylamine − A novel bone-targeting RNA delivery system

Bone-related disorders have become a prevailing concern in older men and postmenopausal women. Traditional methods of treatment, though have benefits, their inability to target specific cells or tissues increases their ineffectiveness and side effects. RNA therapy has emerged as an alternative to conventional therapy owing to its specific targeting ability. However, the lack of appropriate RNA vectors remains a major problem for successful RNA therapy. Here, we designed a delivery system, (SDSSD-PVAm (PS)) based on a cationic polymer, polyvinylamine (PVAm), and a bone-targeting peptide, SDSSD (Serine-Aspartate-Serine-Serine-Aspartate), to deliver a therapeutic RNA, anti-miR-138-5p, to the bone tissue. The results showed that the SDSSD modification not only had no negative effect on the RNA-carrying or protection abilities of PVAm but also improved targeting and RNA delivery to osteoblasts and improve osteogenic potential of the cells by improving the expression of osteogenic genes both at RNA and protein level. Recombinant anti-miR-138-5p delivered through PS was highly enriched in the bone tissue, and the resultant nanoparticles could circulate for a longer time in the blood with negligible toxicity. The results showed that improved RNA delivery through PS significantly increased the rate of bone formation and improved trabecular and cortical bone microarchitecture, resulting in enhanced bone mass in ovariectomy (OVX) and hind limb unloading (HLU) model mice. These results demonstrate that SDSSD-PVAm is a novel RNA delivery system for bone-related disorders, such as osteoporosis.

Effects of Dye Addition on the Rheological Properties of Aqueous Polymer Solutions.

In many commercial applications, polymer-dye interactions are frequently encountered from food to wastewater treatment, and while shear rheology has been well characterized, the extensional properties are not well known. The extensional viscosity ηE and relaxation time λE are the extensional rheological parameters that provide valuable insights into how aqueous polymers respond during deformation, and this study investigated the effect of dyes on the extensional rheology of three different aqueous polymer solutions (e.g., anionic, cationic, and neutral) paired with two different dye salts (e.g., anionic and cationic) using drop pinch-off experiments. We have found that the influence of dyes on the pinch-off dynamics is complex but generally leads to a decrease in, for example, the apparent extensional relaxation time. We have utilized the dripping-onto-substrate method to probe the uniaxial deformation of widely used polymers such as xanthan gum (XG), poly(diallyldimethylammonium chloride) (PDADMAC), and poly(ethylene oxide) (PEO) as the anionic, cationic, and neutral polymers, respectively, paired with either fluorescein (Fl) or methylene blue (MB) as the anionic and cationic dyes, respectively. Polymer-dye pairs with opposite charges (e.g., XG-MB and PDADMAC-Fl) displayed a pronounced decrease in pinch-off times, but even PEO, which is a neutral polymer, resulted in decreased pinch-off times, which was restored by the addition of NaCl. The pinch-off times for the Boger fluid (mixture of poly(ethylene glycol) and PEO), however, were surprisingly uninfluenced by dyes. These results showed that not only did the small addition of dyes strongly decrease the polymer relaxation times, but the relative importance of the dye salts on the polymer pinch-off dynamics was also different from that of pure salts such as NaCl.

Continuously producible aztreonam-loaded inhalable lipid nanoparticles for cystic fibrosis-associated Pseudomonas aeruginosa infections – Development and in-vitro characterization

Cystic fibrosis (CF) is a genetic disorder affecting nearly 105,000 patients worldwide and is characterized by poor respiratory function due to accumulation of thick mucus in the lungs, which not just acts as a physical barrier, but also provides a breeding ground for bacterial infections. These infections can be controlled with the help of antibiotics which can be delivered directly into the lungs for amplifying the local anti-bacterial effect. More than 50 % of CF patients are associated with Pseudomonas aeruginosa infection in their lungs which requires antibiotics such as Aztreonam (AZT). In this study, we prepared inhalable AZT-loaded lipid nanoparticles using Hot-melt extrusion (HME) coupled with probe sonication to target Pseudomonas aeruginosa infection in the lungs. The optimized nanoparticles were tested for physicochemical properties, stability profile, in-vitro aerosolization, and antimicrobial activity against Pseudomonas aeruginosa. The optimized nanoparticles with a PEI concentration of 0.1 % demonstrated a uniform particle size of <50 nm, a spherical shape observed under a transmission electron microscope, and >70 % drug entrapment. Incorporating cationic polymer, PEI, resulted in sustained drug release from the lipid nanoparticles. The in-vitro aerosolization studies exhibited a mass median aerodynamic diameter (MMAD) of <4.3 μm, suggesting deposition of the nanoparticles in the respirable airway. The antimicrobial activity against Pseudomonas aeruginosa showed the minimum inhibitory concentration of the formulation is 2-fold lower than plain AZT. Stability profile showed the formulations are stable after exposure to accelerated conditions. In conclusion, hot-melt extrusion in combination with probe sonication can be used as a potential method for the continuous production of AZT-loaded lipid nanoparticles with enhanced anti-bacterial activity.

Cell membrane-coated mRNA nanoparticles for enhanced delivery to dendritic cells and immunotherapy

Cationic polymers such as polyethylenimine have been considered promising carriers for mRNA vaccines. However, their application is hindered by their inherent toxicity and a lack of targeted delivery capability. These issues need to be addressed to develop effective cancer vaccines. In this study, we investigated whether dendritic cell membrane-coated polyethylenimine/mRNA nanoparticles (DPN) could effectively deliver mRNA to dendritic cells and induce immune responses. For comparison, we employed red blood cell membrane-coated polyethylenimine/mRNA (RPN) and plain polyethylenimine/mRNA polyplex (PN). The dendritic cell membrane coating altered the zeta potential values and surface protein patterns of PN. DPN demonstrated significantly higher uptake in dendritic cells compared to PN and RPN, and it also showed greater mRNA expression within these cells. DPN, carrying mRNA encoding luciferase, enhanced green fluorescent protein, or ovalbumin (OVA), exhibited higher protein expression in dendritic cells than the other groups. Additionally, DPN exhibited favorable mRNA escape from lysosomes post-internalization into dendritic cells. In mice, subcutaneous administration of DPN containing ovalbumin mRNA (DPNOVA) elicited higher titers of anti-OVA IgG antibodies and a greater population of OVA-specific CD8+ T cells than the other groups. In a B16F10-OVA tumor model, DPNOVA treatment resulted in the lowest tumor growth among the treated groups. Moreover, the population of OVA-specific CD8+ T cells was the highest in the DPNOVA-treated group. While we demonstrated DPN's feasibility as an mRNA delivery system in a tumor model, the potential of DPN can be broadly extended for immunotherapeutic treatments of various diseases through mRNA delivery to antigen-presenting cells.

Co-delivery of PROTAC and siRNA via novel liposomes for the treatment of malignant tumors

Targeted elimination of damaged or overexpressed proteins within the tumor serves a pivotal role in regulating cellular function and restraining tumor cell growth. Researchers have been striving to identify safer and more effective methods for protein removal. Here, we propose the synergistic employment of a small molecule degrading agent (PROTAC) and siRNA to attain enhanced protein clearance efficiency and tumor therapeutic effects. Co-delivery liposomes were prepared to facilitate the efficient encapsulation of PROTAC and siRNA. Specifically, the cationic liposome significantly improved the solubility of the insoluble PROTAC (DT2216). The cationic polymer (F-PEI) achieved efficient encapsulation of the nucleic acid drug, thereby promoting endocytosis and enhancing the therapeutic impact of the drug. Both in vivo and in vitro experiments demonstrated remarkable degradation of target proteins and inhibition of tumor cells by the co-delivery system. In conclusion, the co-delivery liposomes furnished a nano-delivery system proficient in effectively encapsulating both hydrophilic and hydrophobic drugs, thereby presenting a novel strategy for targeted combination therapy in treating tumors.

Fluoroamphiphilic polymers exterminate multidrug-resistant Gram-negative ESKAPE pathogens while attenuating drug resistance.

ESKAPE pathogens are a panel of most recalcitrant bacteria that could "escape" the treatment of antibiotics and exhibit high incidence of drug resistance. The emergence of multidrug-resistant (MDR) ESKAPE pathogens (particularly Gram-negative bacteria) accounts for high risk of mortality and increased resource utilization in health care. Worse still, there has been no new class of antibiotics approved for exterminating the Gram-negative bacteria for more than 50 years. Therefore, it is urgent to develop novel antibacterial agents with low resistance and potent killing efficacy against Gram-negative ESKAPE pathogens. Herein, we present a class of fluoropolymers by mimicking the amphiphilicity of cationic antimicrobial peptides. Our optimal fluoroamphiphilic polymer (PD45HF5) displayed selective antimicrobial ability for all MDR Gram-negative ESAKPE pathogens, low resistance, high in vitro cell selectivity, and in vivo curative efficacy. These findings implied great potential of fluoroamphiphilic cationic polymers as promising antibacterial agents against MDR Gram-negative ESKAPE bacteria and alleviating antibiotic resistance.

PH selective fluorometric detection of E. coli using water soluble polyphenothiazine

This work has investigated the use of a novel cationic conjugated polymer, Poly 10-(6-(3-methylimidazolidin-l-yl)hexyl)−9-Phenothiazine (PMP), as a sensing platform for a polymer-based fluorescence sensor for the detection of E. Coli O157:H7. Fourier Transform Infrared Spectroscopy (FTIR), ultraviolet radiation (UV), proton nuclear magnetic resonance (1HNMR), and photoluminescence (PL) analysis were used to characterise the synthesised polymer. The electrostatic interaction between single strand genomic DNA of E.coli (tDNA) and cationic polymer resulted in photoinduced charge transfer (PET) mediated quenching of the fluorescence intensity of PMP, which has been utilized as a tool for the detection DNA of E. coli (tDNA), since the decrease in photoluminescence intensity of cationic polymer was found to be proportional to the concentration of tDNA. The biosensor developed using PMP exhibits sensitive detection of tDNAin the range of 10−18 to 10−21 M concentration with a lowest detection limit of tDNA is 1 × 10−21 M.

Layer-by-layer nanocomposite based on zein and hyaluronic acid for tumor-targeted gene delivery

Gene vectors provide a viable approach to ensuring that therapeutic genes reach the target cells. Polyethyleneimine (PEI), a cationic polymer, was brought into focus on high transfection efficiency as a gene carrier. However, the high cytotoxicity and lack of targeting ability during loading genes remain confusing topics. Herein, Fe3O4 served as the magnetic source, plant extract Zein served as the structural unit loaded with PEI and hyaluronic acid (HA) served as the targeted switch, the Fe3O4/Zein/PEI25k-HA (FeZP25k-HA) was synthesized through an antisolvent approach, and its cytotoxicity, targeting ability and transfection efficiency in HEK 293 T and HeLa cells were further investigated. The FeZP25k-HA exhibited low toxicity at the cellular level, and under external magnetic fields, it revealed a significant enrichment effect, which contributed to enhancing cellular uptake. The FeZP25k (Fe3O4/Zein/PEI25k) modified with HA displayed higher uptake and transfection efficiency in HeLa cells, and excellent tumor targeting ability. This work was expected to offer an innovative strategy to design a safe, efficient magnetic targeted gene delivery system with low toxicity and high transfection efficiency.

Development of fucoidan/polyethyleneimine based sorafenib-loaded self-assembled nanoparticles with machine learning and DoE-ANN implementation: Optimization, characterization, and in-vitro assessment for the anticancer drug delivery

This study aims to develop sorafenib-loaded self-assembled nanoparticles (SFB-SANPs) using the combined approach of artificial neural network and design of experiments (ANN-DoE) and to compare it with other machine learning (ML) models. The central composite design (CCD) and ML algorithms were used to screen the effects of concentrations of both the polymers (polyethyleneimine and fucoidan) on the outcome responses, i.e., particle size and entrapment efficiency with defined constraints. The prediction from different ML models (bootstrap forest, K-nearest neighbors, artificial neural network, generalized regression-lasso and support vector machines) were compared with ANN-DoE model. The ANN-DoE model showed better accuracy and predictability and outperformed all the other models. This depicted that the concept of using ANN and DoE combination approach provided the best, uncomplicated and cost-effective way to optimized the nanoformulations. The optimized formulation generated from the ANN-DoE combined model was further evaluated for characterization and anticancer activity. The optimized SFB-SANPs were prepared using the polyelectrolyte complexation method with Polyethyleneimine (PEI) as a cationic polymer and fucoidan (FCD) as an anionic. The SFB-SANPs were nanometric in size (280.4 ± 0.089 nm) and slightly anionic in nature (zeta potential = −6.03 ± 0.92 mV) with an encapsulation efficiency of 95.56 ± 0.30 %. The drug release from SFB-SANPs was controlled and sustained in the cancer microenvironment (pH 5.0). The SFB-SANPs were compatible with red blood cells (RBCs), and the % hemolysis was found to be <5.0 %. The anticancer activity of the SFB-SANPs exhibited an IC50 at 2.017 ± 0.516 μM against MDMB-231 cells, showing a significantly high inhibitory effect on breast cancer cell lines. Therefore, the nanocarriers developed using various ML tools inherit a huge promise in anticancer drug delivery.

Modifying MSCs-derived EVs with esterase-responsive and charge-reversal cationic polymers enhances bone regeneration

Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) for the treatment of bone defects have been widely reported as a cell-free therapy because of their appropriate stability and biocompatibility. However, EV isolation is expensive and time-consuming. We developed a method of modifying EVs derived from bone marrow MSCs (BMSCs) via the cationic polymer (ERP) with characteristics of charge reversal and esterase response (ERP-EVs). When simply mixing BMSCs-EVs with ERP at a 1:1 ratio, ERP-EVs significantly enhanced the osteogenesis of BMSCs. More EVs were released by ERP in BMSCs than in fibroblasts, realizing the selective release. Last, ERP-EVs were loaded on an nHA/CS-MS scaffold and showed enhanced bone regeneration on rat calvarial bone defects invivo. In general, this study provided an effective strategy to improve cellular uptake and selective release of BMSCs-EVs in bone-related cells, which had great potential to accelerate the clinical practice of BMSCs-EVs-based bone defect repair.