Materials Strategies to Overcome the Foreign Body Response.

The foreign body response (FBR) is an immune-mediated reaction that can occur with most biomaterials and biomedical devices. The FBR initiates a deterioration in the performance of implantable devices, representing a longstanding challenge that consistently hampers their optimal utilization. Over the last decade, significant strides are achieved based on either hydrogel design or surface modifications to mitigate the FBR. This review delves into recent material strategies aimed at mitigating the FBR. Further, the authors look forward to future novel anti-FBR materials from the perspective of clinical translation needs. Such prospective materials hold the potential to attenuate local immune responses, thereby significantly enhancing the overall performance of implantable devices.

Robust, Sprayable, and Multifunctional Hydrogel Coating through a Polycation Reinforced (PCR) Surface Bridging Strategy.

The sprayable hydrogel coatings that can establish robust adhesion onto diverse materials and devices hold enormous potential; however, a significant challenge persists due to monomer hydration, which impedes even coverage during spraying and induces inadequate adhesion post-gelation. Herein, a polycation-reinforced (PCR) surface bridging strategy is presented to achieve tough and sprayable hydrogel coatings onto diverse materials. The polycations offer superior wettability and instant electrostatic interactions with plasma-treated substrates, facilitating an effective spraying application. This PCR-based hydrogel coatings demonstrate tough adhesion performance to inert PTFE and silicone, including remarkable shear strength (161 ± 49 kPa for PTFE), interfacial toughness (198 ± 27 J m-2 for PTFE), and notable tolerance to cyclic tension (10 000 cycles, 200% strain, silicone). Meanwhile, this method can be applied to various hydrogel formulations, offering diverse functionalities, including underwater adhesion, lubrication, and drug delivery. Furthermore, the PCR concept enables the conformal construction of durable hydrogel coatings onto sophisticated medical devices like cardiovascular stents. Given its simplicity and adaptability, this approach paves an avenue for incorporating hydrogels onto solid surfaces and potentially promotes untapped applications.

Comparison study of surface-initiated hydrogel coatings with distinct side-chains for improving biocompatibility of polymeric heart valves.

Polymeric heart valves (PHVs) present a promising alternative for treating valvular heart diseases with satisfactory hydrodynamics and durability against structural degeneration. However, the cascaded coagulation, inflammatory responses, and calcification in the dynamic blood environment pose significant challenges to the surface design of current PHVs. In this study, we employed a surface-initiated polymerization method to modify polystyrene-block-isobutylene-block-styrene (SIBS) by creating three hydrogel coatings: poly(2-methacryloyloxy ethyl phosphorylcholine) (pMPC), poly(2-acrylamido-2-methylpropanesulfonic acid) (pAMPS), and poly(2-hydroxyethyl methacrylate) (pHEMA). These hydrogel coatings dramatically promoted SIBS's hydrophilicity and blood compatibility at the initial state. Notably, the pMPC and pAMPS coatings maintained a considerable platelet resistance performance after 12 h of sonication and 10 000 cycles of stretching and bending. However, the sonication process induced visible damage to the pHEMA coating and attenuated the anti-coagulation property. Furthermore, the in vivo subcutaneous implantation studies demonstrated that the amphiphilic pMPC coating showed superior anti-inflammatory and anti-calcification properties. Considering the remarkable stability and optimal biocompatibility, the amphiphilic pMPC coating constructed by surface-initiated polymerization holds promising potential for modifying PHVs.

Poly(Glutamic Acid-Lysine) Hydrogels with Alternating Sequence Resist the Foreign Body Response in Rodents and Non-Human Primates.

The foreign body response (FBR) to implanted biomaterials and biomedical devices can severely impede their functionality and even lead to failure. The discovery of effective anti-FBR materials remains a formidable challenge. Inspire by the enrichment of glutamic acid (E) and lysine (K) residues on human protein surfaces, a class of zwitterionic polypeptide (ZIP) hydrogels with alternating E and K sequences to mitigate the FBR is prepared. When subcutaneously implanted, the ZIP hydrogels caused minimal inflammation after 2 weeks and no obvious collagen capsulation after 6 months in mice. Importantly, these hydrogels effectively resisted the FBR in non-human primate models for at least 2 months. In addition, the enzymatic degradability of the gel can be controlled by adjusting the crosslinking degree or the optical isomerism of amino acid monomers. The long-term FBR resistance and controlled degradability of ZIP hydrogels open up new possibilities for a broad range of biomedical applications.

Microneedle patch with "spongy coating" to co-load multiple drugs to treat multidrug-resistant melanoma.

Melanoma is the most aggressive skin malignancy that continues to increase in worldwide. The transferability and multidrug resistance lead to a high fatality rate. Synergistic administration of hydrophilic carboplatin (CBP) and hydrophobic vorinostat (SAHA) can be a reliable way to treat multidrug-resistant melanoma. However, the different physicochemical properties of multiple drugs make it difficult to achieve a convenient co-loading and an ideal synergistic treatment efficacy. To solve the problem, a microneedle patch with a porous "spongy coating" (PF-MNP) was fabricated. Firstly, (polyacrylic acid/polyethyleneimine)10 multilayers were fabricated on polymethyl methacrylate MNP. Then a "spongy coating" was achieved by acid treatment and freeze-drying. Due to the capillary effect, hydrophobic SAHA and hydrophilic CBP could be conveniently adsorbed step-by-step. The two drugs could distribute evenly on the surface, and the morphology of MNP remained good. The loading content of SAHA and CBP was easily regulated by adjusting the concentration of the adsorption solution, and MNP could quickly release most drugs within 30 min. The final in vivo experiments proved that CBP/SAHA co-loaded PF-MNP had the best therapeutic efficiency for multidrug-resistant melanoma. The MNP with a "spongy coating" showed potential to be a safe and efficient transdermal delivery platform for multiple drugs.

Targeted delivery of liver X receptor agonist to inhibit neointimal hyperplasia by differentially regulating cell behaviors.

Restenosis induced by neointimal hyperplasia is one of the key reasons limiting the long-term success of cardiovascular interventional therapy. However, it remains a serious challenge to completely overcome restenosis because of the dilemma of simultaneously activating human umbilical vein endothelial cells (HUVECs) and inhibiting human aortic smooth muscle cells (HASMCs). Herein, we developed a targeted nanomedicine encapsulating the liver X receptor (LXR) agonist, T0901317, for differentially regulating the behaviors of HUVECs and HASMCs. The stimulatory effect on HUVEC proliferation/migration and the inhibitory effect on HASMC proliferation/migration were confirmed in vitro, respectively. In the co-culture system, the competitiveness of HUVECs over HASMCs was notably improved after being treated with T0901317-loaded liposomes. Compared to free T0901317 and non-targeted liposomes, the type IV collagen (Col-IV) targeted liposomes could accumulate in the vascular injured area more effectively and inhibit neointimal hyperplasia in a balloon-induced rat carotid artery injury model. Therefore, targeted delivery of LXR agonist might be a very promising therapeutic strategy for anti-restenosis therapy.

Mir-22-incorporated polyelectrolyte coating prevents intima hyperplasia after balloon-induced vascular injury.

Drug-coated balloons (DCBs) offer potential to deliver drugs to treat coronary lesions but without leaving permanent implants behind. Paclitaxel and sirolimus are anti-proliferation drugs that are commonly used in commercially available DCBs. However, these drugs present significant cytotoxicity concern and low efficacy in vivo. Here, we use microRNA-22 (miR-22) as balloon loaded drugs and polyelectrolyte complexes (PECs) polyethyleneimine/polyacrylic acid (PEI/PAA) as balloon coatings to establish a new DCB system through the ultrasonic spray method. The PEI/PAA forms a stable and thin coating on the balloon, which resulted in a good transfer capacity to the vessel wall both in vitro and in vivo. miR-22 that could modulate smooth muscle cell (SMC) phenotype switching is incorporated into the PEI/PAA coating and shows a sustained release profile. The PEI/PAA/miR-22 coated balloon successfully inhibits intima hyperplasia after balloon-induced vascular injury in a rat model through decreasing proliferative SMCs via the miR-22-methyl-CpG binding protein 2 (MECP2) axis. Our findings indicate that balloons coated with PEI/PAA/miR-22 have great potential to be promising DCBs in the treatment of cardiovascular disease.

A NIR-II emissive polymer AIEgen for imaging-guided photothermal elimination of bacterial infection.

The development of antibiotics resistance has made multidrug-resistant (MDR) bacterial infection one of the most serious global health issues. Photothermal therapy (PTT) is an emerging therapeutic mode which can be applied to bacterial infection without inducing resistance. Moreover, enhanced therapeutic efficacy and less tissue damage can be realized with NIR-II fluorescence imaging (FLI) guided PTT. Herein, a polymeric luminogen with aggregation-induced emission (AIEgens) characteristics, poly(dithieno[3,2-b:2',3'-d]pyrrole-benzo[1,2-c:4,5-c']bis([1,2,5]thiadiazole)) (PDTPTBT), was synthesized and used as a photothermal agent for PTT of bacterial infections. PDTPTBT was encapsulated into liposomes (L-PDTPTBT) for improved water dispersibility. Upon 808 nm NIR irradiation, L-PDTPTBT can eliminate multiple bacteria including the Gram-positive methicillin-resistant Staphylococcus aureus and Enterococcus faecalis, the Gram-negative Escherichia coli and Pseudomonas aeruginosa. Serious damage of bacterial membrane and leakage of cytoplasm is observed after photothermal treatment using L-PDTPTBT. The potential of the formulation has been demonstrated in two infected animal models: (i) a subcutaneous abscess model and (ii) a diabetic skin infection model. In the diabetic skin infection model, the death of mice is largely suppressed and the wounds can heal more quickly with treatment of L-PDTPTBT under NIR irradiation. The excellent photothermal bactericidal ability and low cytotoxicity make L-PDTPTBT potential candidate for treating MDR bacterial infections in the future.

The influence of cyclodextrin modification on cellular uptake and transfection efficiency of polyplexes.

Cyclodextrin-modified polycations have been studied widely due to their low cytotoxicity, low immunogenicity and the ability to form inclusion complexes. However, the influence of CD modification on cellular uptake and transfection efficiency of polyplexes is still unclear. In this research, cyclodextrin-modified polyethylenimines (PEI-CD) with different CD-grafting levels were synthesized, which were named PEI-CD(15) and PEI-CD(41), respectively, according to the CD number per PEI chain. CD modification showed great influence on the DNA condensation ability of the polycation. PEI-CD(15) could protect DNA completely above N/P ratio of 2. The particle sizes of these polyplexes were about 120 nm. However, PEI-CD(41) could not protect DNA below N/P of 6, and PEI-CD(41)/DNA polyplexes were larger than 1 µm, even at N/P ratio of 10. Therefore, this research was mainly focused on PEI-CD(15). It was interesting that the PEI-CD(15)/DNA polyplexes at N/P ratio of 8 and 10 displayed excellent stability in physiological salt conditions, probably due to the hydration shell of CDs. The influence of CD modification on the cellular uptake and transfection efficiency of polyplexes depended on the type of the cells. Uptake inhibition experiments indicated that PEI/DNA polyplexes were internalized by HEK293T cells by both clathrin-mediated endocytosis and caveolae-mediated endocytosis. The route of caveolae-mediated endocytosis was significantly promoted after CD modification. So the cell uptake and transfection efficiency of PEI-CD(15)/DNA polyplexes were significantly improved for HEK293T cells. However, the uptake and transfection efficiency of PEI-CD(15)/DNA polyplexes in HepG2 cells was similar to that of PEI/DNA polyplexes, probably due to the lack of endogenous caveolins.

Polydopamine nanoparticles with different sizes for NIR-promoted gene delivery and synergistic photothermal therapy.

The combination of photothermal therapy and gene therapy has received increasing attention in tumor treatment. However, how to improve synergistic efficacy has become a new challenge. NIR light has a great potential in tumor treatment because of its considerable penetration depth and spatiotemporal controllability. Polydopamine is a popular photothermal conversion agent, which has desirable photothermal conversion ability and good biocompatibility. In this research, polydopamine-polyethyleneimine nanoparticles with diameters of 13 nm (SPPNPs) and 236 nm (LPPNPs) were prepared as gene carriers. The size of polydopamine nanoparticles had great effect on the complexes formation, photothermal conversion ability and gene transfection efficiency. After loading gene, the SPPNPs/gene and LPPNPs/gene complexes were about 60-80 nm and 240 nm respectively, indicating different styles of complexes formation. Both SPPNPs/gene and LPPNPs/gene complexes without NIR irradiation could achieve similar gene transfection efficiency as commercial lipofectamine 2000, while with lower cytotoxicity. Due to better photothermal conversion ability, the transfection level of LPPNPs/pGL-3 complexes increased to 4.5 times after NIR irradiation (2.6 W/cm2, 15 min), which ascribed to the quick escape of gene complexes from the endosome. The produced heat under NIR irradiation could also ablate tumor cells. So LPPNPs were chosen to deliver tumor suppressor gene p53 DNA to investigate the synergistic efficacy of gene/photothermal therapy. The tumor in KB tumor-bearing mice was almost eliminated after intratumoral injection, and the tumor inhibition efficacy of gene/photothermal synergistic therapy achieved to 99%. By combining NIR-promoted gene transfection and gene/photothermal synergistic therapy, the LPPNPs hold great promise in practical tumor treatment.

A gene-coated microneedle patch based on industrialized ultrasonic spraying technology with a polycation vector to improve antitumor efficacy.

A coated microneedle patch is a reliable way to load gene on a surface as a transdermal gene delivery platform. But there are many limitations to the traditional methods to fabricate a coated microneedle patch, such as the fact that they are time consuming or the difficulty in controlling the loading content. In this research, ultrasonic spraying technology, as an industrialized production method, was first used to fabricate a gene-coated microneedle patch. First, the p53 expression plasmid (p53 DNA) was ultrasonically sprayed on a polycaprolactone (PCL) microneedle patch (D@MNP). To promote the transfection efficiency, polycation polyethylenimine (PEI), as a vector, was then ultrasonically sprayed on D@MNP (P@D@MNP). From the experimental results, although two layers were sprayed step by step, no obvious stratification could be observed. The vector PEI interweaved with genes and inhibited the gene release profile, but it changed the released naked genes to positively charged complexes, which would promote gene transfection efficiency. In subsequent in vivo experiments, the anti-tumor efficacy of the "P@D@MNP treated group" could reach 84.7%, although it had the lowest gene release profile. In contrast, the anti-tumor efficacy of the "intravenous injection group" and "D@MNP treated group" was only 24.3% and 59.3%, respectively. Overall, P@D@MNP was a safe and efficient device to treat the subdermal tumor. Ultrasonic spraying technology provided an industrialized method to fabricate the coated microneedle patch as a transdermal gene/drug delivery platform.

The Relationship Between Osteoporosis and Intestinal Microbes in the Henan Province of China.

Osteoporosis (OP) is a chronic disease in the elderly, and China is entering an aging demographic trend. In recent years, increasing evidence has demonstrated that probiotics can treat osteoporosis. This study aimed to explore the relevant mechanisms and to validate the beneficial effect on osteoporosis by high-throughput metagenome-wide gene sequencing in humans. In this study, compared with controls, several species had altered abundances, and specific functional pathways were found in the OP group. At the species level, the species that had increased in OP individuals were positively correlated to bone resorption markers and negatively correlated to 25-OH-D3 and bone formation markers, with Streptococcus sanguinis showing the strongest relevance, followed by Streptococcus gordonii, Actinomyces odontolyticus, and Olsenella unclassified. Additionally, Actinomyces graevenitzii, enriched in the OP group, was positively correlated to inflammation indicators that included white blood cell (WBC), neutrophil count (NEC), and the neutrophil-to-lymphocyte ratio (NLR) (p < 0.05). Conversely, the levels of Akkermansia muciniphila, Bacteroides eggerthii, Bacteroides fragilis, Bacteroides uniformis, and Butyricimonas synergistic were increased in the control group, which had a negative correlation with bone resorption markers and positive correlation with bone formation markers and 25-OH-D3. Additionally, Bacteroides fragilis had a negative correlation with inflammation indicators (WBC, NEC, and NLR) and the above pathways (p < 0.05). Functional prediction revealed that 106 metabolic pathways, enriched in the OP group, were significantly higher than in the control group (p < 0.05). In particular, pathways related to LPS biosynthesis, phytate degradation, lactate acid, and ethanol fermentation were more abundant in the OP group than in the control and were positively related to WBC and NEC. Taken together, several species with altered abundances and specific functional pathways were found in OP individuals. The role of phytases in OP provides novel epidemiological evidence to elucidate the underlying microbiota-relevant mechanisms in bone mineralization and should be explored further.

A miRNA stabilizing polydopamine nano-platform for intraocular delivery of miR-21-5p in glaucoma therapy.

The elevation of intraocular pressure (IOP) is an important risk factor in the development of primary open angle glaucoma (POAG), which is the main cause of irreversible vision loss. miRNAs are promising new anti-glaucoma therapeutic agents. However, the low stability and cellular transfection of miRNA in vivo hinder its further application. This study aims to investigate the use of polydopamine-polyethylenimine nanoparticles (PDA/PEI NPs) as miRNA carriers in the treatment of ocular hypertension and glaucoma. The in vitro study proves that the carrier preserves the activity of nucleic acid for a long period. Besides, it has comparable transfection efficiency with commercially available vehicles, while having lower cytotoxicity. It has been demonstrated in the animal model that PDA/PEI NPs successfully reach the target tissues without an obvious inflammatory response. PDA/PEI NPs/miR-21-5p increases the permeability of porcine angular aqueous plexus cells, thereby reducing IOP by facilitating the conventional outflow pathway at least partially through the pathway involving endothelial nitric oxide synthase. Our results indicate that PDA/PEI NPs/miR-21-5p is a promising anti-glaucoma drug for treating POAG. And the delivery strategy may be extended to other gene therapy in treating intraocular diseases.

pH-responsive polydopamine nanoparticles for photothermally promoted gene delivery.

Recently, stimuli-responsive gene carriers have been widely studied to overcome the extra- and intracellular barriers in cancer treatment. In this study, we modified polydopamine nanoparticles with low-molecular weight polyethylenimine (PEI1.8k) and polyethylene glycol-phenylboronic acid (PEG-PBA) to prepare pH-responsive gene carrier PDANP-PEI-rPEG. PBA and polydopamine could form pH-responsive boronate ester bonds. Non-responsive PDANP-PEI-nPEG and non-PEGylated PDANP-PEI were also studied as control. Both PDANP-PEI-rPEG/DNA and PDANP-PEI-nPEG/DNA complexes remained stable in the pH environment of blood circulation or extracellular delivery (pH 7.4) owing to the PEG modification. And after being internalized into endosomes, the boronate ester bonds could be cleaved. The pH responsive ability of PDANP-PEI-rPEG might facilitate complexes dissociation and gene release inside cells. The transfection level of PDANP-PEI-rPEG/DNA complexes was about 100 times higher than that of PDANP-PEI-nPEG/DNA complexes with the same mass ratios. Moreover, after NIR light irradiation at the power density of 2.6 W/cm2 for 20 min, the good photothermal conversion ability of PDANP resulted in quick endosomal escape. The transfection level of PDANP-PEI-rPEG/DNA complexes doubled, even higher than that of lipofectamine 2000/DNA complexes. This was also confirmed by Bafilomycin A1 inhibition test and CLSM observation. In response to the acidic pH within cancer cells and the NIR light irradiation, the PDANP-PEI-rPEG carrier could overcome multiple obstacles in gene delivery, which was promising for further application in gene therapy.

Performance of AmpFire HPV assay on neck cervical lymph node aspirate and oropharyngeal samples.

Early determination of high-risk human papillomaviruses causing oropharyngeal squamous cell carcinomas (OPSCC) may influence treatment. The objectives were to evaluate the performance of a new rapid isothermal nucleic acid amplification point of care HPV test (AmpFire HPV) on fine needle neck aspirates (FNA) of cervical lymph nodes and oropharyngeal swabs and saliva (OPS) which had been previously tested by the cobas HPV assay. The comparison was performed on 56 FNA and 81 OPS. The two assays showed strong agreement (94.6 %, K = 0.88) on FNA and fair agreement (65.4 %, K = 0.34) on OPS. AmpFire HPV performed on FNA demonstrated a sensitivity of 76.7 % and specificity of 81.8 % for the prediction of p16 antigens in OPSCC with results available in 1.5 h.

Biodegradable phosphorylcholine copolymer for cardiovascular stent coating.

Phosphorylcholine (PC) based polymer coatings with excellent biocompatibility have shown successful commercialization in drug-eluting stents. However, poor degradability represents a challenge in the application of biodegradable stents. Herein, a biodegradable phosphorylcholine copolymer is developed based on one-step radical ring-opening polymerization (RROP). This copolymer was synthesized by copolymerization of a PC unit, degradable ester (2-methylene-1,3-dioxepane, MDO) unit and non-degradable butyl methacrylate (BMA) unit, which showed ratio controllability by changing the monomer ratio during polymerization. We demonstrated that the copolymer with the ratio of 34% MDO, 19% MPC and 47% BMA could form a stable coating by ultrasonic spray, and showed good blood compatibility, anti-adhesion properties, biodegradability, and rapamycin eluting capacity. In vivo study revealed its promising application as a biodegradable stent coating. This work provides a facile path to add biodegradability into PC based polymers for further bio-applications.

Cutaneous microenvironment responsive microneedle patch for rapid gene release to treat subdermal tumor.

Transdermal gene therapy is a useful treatment for many skin lesions. By penetrating stratum corneum directly, microneedle patch (MNP) has been widely investigated to improve transdermal gene delivery. However, considering the operability and patience compliance, quick gene release was required after insertion. In this research, by utilizing acidic cutaneous environment, pH-responsive polyelectrolyte multilayers (PEM) were coated on the surface of polycaprolactone (PCL) microneedles by layer-by-layer assembly to realize rapid gene release. Dimethylmaleic anhydride-modified polylysine (PLL-DMA), a charge reversible polymer, was introduced to PEM. The PEM composed of two parts: the transition layers of (PLL-DMA/polyethyleneimine)12 and the gene-loaded layers of (p53 expression plasmid/polyethyleneimine)16. Microneedle patch modified with such PEM was marked as tr-MNP. In following experiment, Hoechst 33258 dyed model DNA was used to track modification process, fluorescent intensity of tr-MNP was obviously strengthened while the number of bilayers increased and the morphology could be maintained. Each tr-MNP could load 31µg model DNA and improve gene release. To prove this character, MNP without transition layers (ntr-MNP) was fabricated as control. Tr-MNP could release 33% of model DNA in simulative cutaneous environment (phosphate buffer saline; pH=5.5) while ntr-MNP could only release 4%. That was because PLL-DMA could achieve charge reversal in acidic cutaneous environment, leading to the collapse of transition layers and promoted the gene release. In vivo experiment showed tumor inhibit efficacy of tr-MNP treated mice could reach 90.1% while that of ntr-MNP treated mice and intravenous administration mice was only 46.4% and 30.5%. Overall, the pH-responsive gene loaded MNP could treat subcutaneous tumor efficiently and showed potential to be a platform to load many biomacromolecule.

Construction of caged polyplexes with a reversible intracellular unpacking property to improve stability and transfection.

Cross-linking of protein macromonomers accompanies the assembly of viral particles, which provides the virus with high stability in the host. Following inspiration, caged polyplexes were fabricated via a biomimetic cross-linker. Thiolated polyethylenimine was synthesized and showed sufficient DNA condensation ability. Spherical particles with a diameter of about 150nm were formed at an N/P ratio of 10. Shell-cross-linked polyplexes were then constructed by the oxidation of thiol groups in air. All the results indicate that the cross-linking shell via disulfide bonds could improve the stability of polyplexes in the physiological condition and showed a reversible unpacking property at the intracellular GSH concentration. By selecting the proper preparation conditions, polyplexes caged via a biomimetic cross-linker could efficiently release DNA for transfection.

A facile entrapment approach to construct PEGylated polyplexes for improving stability in physiological condition.

PEGylated polyplexes had been proved to improve the stability of DNA complexes. However, the conjugation reaction might reduce the capacity of efficient DNA complexation. Herein we described an easy and favorable approach to construct PEGylated polyplexes via entrapping poly(ethylene glycol) cholesterol ether (CPEG) into polyplexes. It was of interest to find the addition sequence of CPEG had great effect on the stability of polyplexes in physiological salt concentration. The addition of CPEG into the formed PEI(25k)/DNA polyplexes had no effect to improve the stability. Whereas by the "CPEG first" method of adding CPEG and PEI(25k) mixture into the DNA solution, the PEI(25k)/CPEG/DNA polyplexes showed excellent anti-aggregation effect and enhanced transfection efficiency in physiological condition. The difference performance might be explained by the possibility of CPEG entrapment. By the "CPEG first" method, PEGylated polyplexes was constructed due to the hydrophobic interaction between the cholesterol group of CPEG and hydrophobic charged-compensated core. The PEG coating significantly improved the stability of polyplexes in physiological condition. This facile entrapment approach to prepare PEGylated polyplexes might have great potential in non-viral gene delivery research and application.

Regulation the morphology of cationized gold nanoparticles for effective gene delivery.

Recent research indicated that the morphology of nanoparticles could result in distinct biological behaviors, thus played an important role in designing efficient gene delivery systems. Among them, gold nanoparticles (AuNPs) with various shapes were widely studied due to the good biocompatibility and easy modification ability. Our recent research indicated that polyethyleneimine-g-bovine serum albumin (BSA-PEI) as non-viral gene vector showed good colloid stability and high transfection efficiency. In this work, BSA-PEI was utilized to modify gold nanospheres (AuNSs) and gold nanorods (AuNRs) to investigate the influence of the morphology on gene delivery. Both AuNS@BSA-PEI and AuNR@BSA-PEI nanoparticles condensed DNA effectively at N/P ratio above 5 and maintained spherical or rod-like morphology respectively. Due to the higher surface charge density at the tips, the rod-like gene complexes were prone to use the tips to contact with cell membrane, which facilitated to be uptaked by HepG2 cells. The endocytosis inhibition experiments showed some differences in the endocytic pathway. Gene transfection experiment showed that the rod-like complexes had almost 100-fold higher of transfection level than that of spherical complexes at the N/P ratio of 20. This work provided a potential strategy for further design of gene vectors with improved transfection results by adjusting the morphology of gene vectors.