Biomimetic Nanoparticles Research Articles

Biomimetic Boron Nitride Nanoparticles for Targeted Drug Delivery and Enhanced Antitumor Activity.

Boron nitride nanomaterials are being increasingly recognized as vehicles for cancer drug delivery that increase drug loading and control drug release because of their excellent physicochemical properties and biocompatibility. However, these nanoparticles are often cleared rapidly by the immune system and have poor tumor targeting effects. As a result, biomimetic nanotechnology has emerged to address these challenges in recent times. Cell-derived biomimetic carriers have the characteristics of good biocompatibility, long circulation time, and strong targeting ability. Here, we report a biomimetic nanoplatform (CM@BN/DOX) prepared by encapsulating boron nitride nanoparticles (BN) and doxorubicin (DOX) together using cancer cell membrane (CCM) for targeted drug delivery and tumor therapy. The CM@BN/DOX nanoparticles (NPs) were able to target cancer cells of the same type on its own initiative through homologous targeting of cancer cell membranes. This led to a remarkable increase in cellular uptake. In vitro simulation of an acidic tumor microenvironment could effectively promote drug release from CM@BN/DOX. Furthermore, the CM@BN/DOX complex exhibited an excellent inhibitory effect against homotypic cancer cells. These findings suggest that CM@BN/DOX are promising in targeted drug delivery and potentially personalized therapy against their homologous tumor.

Biomimetic Nanoparticle-Mediated Target Delivery of Hypoxia-Responsive Plasmid of Angiotensin-Converting Enzyme 2 to Reverse Hypoxic Pulmonary Hypertension.

Hypoxic pulmonary hypertension (HPH) is characterized by pulmonary vascular sustained constriction and progressive remodeling, which are initiated by hypoxia then with hypoxia-induced additive factors including pulmonary vascular endothelium injury, intrapulmonary angiotension system imbalance, and inflammation. Now HPH is still an intractable disease lacking effective treatments. Gene therapy has a massive potential for HPH but is hindered by a lack of efficient targeted delivery and hypoxia-responsive regulation systems for transgenes. Herein, we constructed the hypoxia-responsive plasmid of angiotensin-converting enzyme 2 (ACE2) with endothelial-specific promoter Tie2 and a hypoxia response element and next prepared its biomimetic nanoparticle delivery system, named ACE2-CS-PRT@PM, by encapsulating the plasmid of ACE2 with protamine and chondroitin sulfate as the core then coated it with a platelet membrane as a shell for targeting the injured pulmonary vascular endothelium. ACE2-CS-PRT@PM has a 194.3 nm diameter with a platelet membrane-coating core-shell structure and a negatively charged surface, and it exhibits higher delivery efficiency targeting to pulmonary vascular endothelium and hypoxia-responsive overexpression of ACE2 in endothelial cells in a hypoxia environment. In vitro, ACE2-CS-PRT@PM significantly inhibited the hypoxia-induced proliferation of pulmonary smooth muscle cells. In vivo, ACE2-CS-PRT@PM potently ameliorated the hemodynamic dysfunction and morphological abnormality and largely reversed HPH via inhibiting the hypoxic proliferation of pulmonary artery smooth muscle cells, reducing pulmonary vascular remodeling, restoring balance to the intrapulmonary angiotension system, and improving the inflammatory microenvironment without any detectable toxicity. Therefore, ACE2-CS-PRT@PM is promising for the targeted gene therapy of HPH.

ROS-Scavenging Hydrogels Synergize with Neural Stem Cells to Enhance Spinal Cord Injury Repair via Regulating Microenvironment and Facilitating Nerve Regeneration.

Although stem cell-based therapy is recognized as a promising therapeutic strategy for spinal cord injury (SCI), its efficacy is greatly limited by local reactive oxygen species (ROS)-abundant and hyper-inflammatory microenvironments. It is still a challenge to develop bioactive scaffolds with outstanding antioxidant capacity for neural stem cells (NSCs) transplantation. In this study, albumin biomimetic cerium oxide nanoparticles (CeO2 @BSA nanoparticles, CeNPs) are prepared in a simple and efficient manner and dispersed in gelatin methacryloyl to obtain the ROS-scavenging hydrogel (CeNP-Gel). CeNP-Gel synergistically promotes neurogenesis via alleviating oxidative stress microenvironments and improving the viability of encapsulated NSCs. More interestingly, in the presence of CeNP-Gel, microglial polarization to anti-inflammatory M2subtype are obviously facilitated, which is further verified to be associated with phosphoinositide 3-kinase/protein kinase B pathway activation. Additionally, the injectable ROS-scavenging hydrogel is confirmed to induce the integration and neural differentiation of transplanted NSCs. Compared with the blank-gel group, the survival rate of NSCs in CeNP-Gel group is about 3.5times higher, and the neural differentiation efficiency is about 2.1times higher. Therefore, the NSCs-laden ROS-scavenging hydrogel represents a comprehensive strategy with great application prospect for the treatment of SCI through comprehensively modulating the adverse microenvironment.

RGD peptide modified RBC membrane functionalized biomimetic nanoparticles for thrombolytic therapy

In recent years, the fabrication of nano-drug delivery systems for targeted treatment of thrombus has become a research hotspot. In this study, we intend to construct a biomimetic nanomedicine for targeted thrombus treatment. The poly lactic-co-glycolic acid (PLGA) was selected as the nanocarrier material. Then, urokinase and perfluoro-n-pentane (PFP) were co-loaded into PLGA by the double emulsification solvent evaporation method to prepare phase change nanoparticles PPUNPs. Subsequently, the RGD peptide-modified red blood cell membrane (RBCM) was coated on the surface of PPUNPs to prepare a biomimetic nano-drug carrier (RGD-RBCM@PPUNPs). The as-prepared RGD-RBCM@PPUNPs possessed a “core-shell” structure, have good dispersibility, and inherited the membrane protein composition of RBCs. Under ultrasound stimulation, the loaded urokinase could be rapidly released. In vitro cell experiments showed that RGD-RBCM@PPUNPs had good hemocompatibility and cytocompatibility. Due to the coated RGD-RBC membrane, RGD-RBCM@PPUNPs could effectively inhibit the uptake of macrophages. In addition, RGD-RBCM@PPUNPs showed better thrombolytic function in vitro. Overall, the results suggested that this biomimetic nanomedicine provided a promising therapeutic strategy for the targeted therapy of thrombosis.Graphical

Doxorubicin Detoxification in Healthy Organs Improves Tolerability to High Drug Doses for Enhanced Antitumor Therapy.

With its well-documented toxicity, the use of doxorubicin (Dox) for cancer treatment requires trade-offs between safety and effectiveness. This limited use of Dox also hinders its functionality as an immunogenic cell death inducer, thus impeding its usefulness for immunotherapeutic applications. Here, we develop a biomimetic pseudonucleus nanoparticle (BPN-KP) by enclosing GC-rich DNA within erythrocyte membrane modified with a peptide to selectively target healthy tissue. By localizing treatment to organs susceptible to Dox-mediated toxicity, BPN-KP acts as a decoy that prevents the drug from intercalating into the nuclei of healthy cells. This results in significantly increased tolerance to Dox, thereby enabling the delivery of high drug doses into tumor tissue without detectable toxicity. By lessening the leukodepletive effects normally associated with chemotherapy, dramatic immune activation within the tumor microenvironment was also observed after treatment. In three different murine tumor models, high-dose Dox with BPN-KP pretreatment resulted in significantly prolonged survival, particularly when combined with immune checkpoint blockade therapy. Overall, this study demonstrates how targeted detoxification using biomimetic nanotechnology can help to unlock the full potential of traditional chemotherapeutics.

Ultrasound-Responsive Biomimetic Superhydrophobic Drug-Loaded Mesoporous Silica Nanoparticles for Treating Prostate Tumor.

Interfacial nanobubbles on a superhydrophobic surface can serve as ultrasound cavitation nuclei for continuously promoting sonodynamic therapy, but their poor dispersibility in blood has limited their biomedical application. In this study, we proposed ultrasound-responsive biomimetic superhydrophobic mesoporous silica nanoparticles, modified with red blood cell membrane and loaded with doxorubicin (DOX) (F-MSN-DOX@RBC), for RM-1 tumor sonodynamic therapy. Their mean size and zeta potentials were 232 ± 78.8 nm and -35.57 ± 0.74 mV, respectively. The F-MSN-DOX@RBC accumulation in a tumor was significantly higher than in the control group, and the spleen uptake of F-MSN-DOX@RBC was significantly reduced in comparison to that of the F-MSN-DOX group. Moreover, the cavitation caused by a single dose of F-MSN-DOX@RBC combined with multiple ultrasounds provided continuous sonodynamic therapy. The tumor inhibition rates in the experimental group were 71.5 8 ± 9.54%, which is significantly better than the control group. DHE and CD31 fluorescence staining was used to assess the reactive oxygen species (ROS) generated and the broken tumor vascular system induced by ultrasound. Finally, we can conclude that the combination of anti-vascular therapy, sonodynamic therapy by ROS, and chemotherapy promoted tumor treatment efficacy. The use of red blood cell membrane-modified superhydrophobic silica nanoparticles is a promising strategy in designing ultrasound-responsive nanoparticles to promote drug-release.

Cancer cell membrane camouflaging mesoporous nanoplatform interfering with cellular redox homeostasis to amplify photodynamic therapy on oral carcinoma

The efficacy of photodynamic therapy (PDT) is still limited by the inefficient utilisation of generated ROS in tumours due to cellular redox homeostasis. To improve the therapeutic efficacy for oral carcinoma, biomimetic cell membrane-coated mesoporous nanoplatform was tailored to interfere with cellular redox homeostasis for amplified PDT. In this study, CAL-27 cancer cell membrane (CM) was encapsulated onto the mesoporous silica NPs (MSN), which were preloaded with Chlorin e6 (Ce6) and Curcumin (Cur). The biomimetic nanoparticles displayed a size of around 120 nm, which had excellent cytotoxicity under a laser and increased uptake ability to tumour cell. After internalised by cancer cells, the released Cur could effectively disturb ROS-defence system by suppressing TrxR activity, and decreasing TrxR-2 expression (p < 0.05), leading to enhanced cancer cell killing ability of PDT. The biomimetic system was found to selectively accumulate in the tumour due to its homologous targeting capability and inhibit tumour growth significantly. In a word, the biomimetic nanoplatform apparently enhanced the therapeutic effect of PDT on tumours by Cur disturbing the ROS-defence system, which exhibited a new way to enhance PDT.

Abstract 2709: Leukosome-based siRNA strategy for targeting ribosomal protein L39 (RPL39) in metaplastic breast cancer

Abstract Metaplastic breast cancer (MpBC) is a rare and highly aggressive subset accounting for &amp;lt;5% of all BCs. Clinically, MpBCs exhibit the most dismal prognosis of all BC subtypes, with a median survival rate of 8 months in patients with metastatic disease. The main therapeutic option for MpBC remains standard chemotherapy, despite known resistance to most cytotoxic drugs. We recently reported that ~40% of MpBC patient samples display a gain-of-function oncogenic mutation (A14V) in ribosomal protein RPL39, which is responsible for treatment resistance, cancer stem cell self-renewal, and lung metastases. We also showed that high RPL39 levels were associated with worse survival in patients with MpBC. Collectively, these findings support the rationale of targeting this ubiquitous genetic marker in MpBC. This study was aimed to design an innovative targeted therapy against RPL39 by combining a small interfering RNA (siRNA) strategy (siRPL39) with biomimetic lipid nanoparticle (LNP) technology for in vivo delivery to MpBC cells. These LNPs referred to as “leukosomes” incorporate membrane proteins from circulating leukocytes to facilitate evasion of immune clearance, enhance tropism towards inflamed endothelium such as the tumor-associated one, and improve siRNA internalization into the tumor mass. For leukosomes synthesis, we adapted a microfluidic device to incorporate membrane proteins from leukocytes within lipid bilayers. This technique retained all the physical and biological features of leukosomes, combined with high siRNA loading efficiency. We evaluated in vitro uptake and efficacy of siRPL39-loaded leukosomes in MpBC cell lines. We found that fluorescently labeled siRPL39 was rapidly internalized by leukosomes into MpBC cells demonstrating efficient and uniform uptake without inducing cytotoxicity. Treatment of MpBC cells with siRPL39-loaded leukosomes exhibited significantly knockdown of RPL39 mRNA, further supporting that the observed siRNA internalization results in potent and specific gene silencing. Notably, siRPL39-loaded leukosomes inhibited in vitro cell proliferation as compared with control siRNA leukosomes, indicating a key role of RPL39 in MpBC growth. Next, we sought to evaluate functional gene silencing of siRPL39-loaded leukosomes in vivo. We established MpBC patient-derived xenografts (PDXs) in the mammary fat pad of humanized NSG mice. We revealed that leukosomes formulation enables siRPL39 accumulation and functional gene silencing in MpBC tumors after local administration, without causing overt toxicity. Overall, our findings highlight RPL39 as a novel therapeutic target in MpBC and provide proof of principle for the development of leukosome-based siRNA drugs to improve delivery to cancer cells. Ongoing studies are directed to evaluate biodistribution, in vivo silencing and therapeutic effects of siRPL39-leukosomes after systemic administration. Citation Format: Maria Florencia Chervo, Chiara Mancino, Federica Giordano, Tejaswini P. Reddy, Wei Qian, Jianying Zhou, Liliana Guzman-Rojas, Roberto R. Rosato, Francesca Taraballi, Jenny C. Chang. Leukosome-based siRNA strategy for targeting ribosomal protein L39 (RPL39) in metaplastic breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2709.

Nanovaccines for cancer immunotherapy: Focusing on complex formation between adjuvant and antigen.

As an interesting cancer immunotherapy approach, cancer vaccines have been developed to deliver tumor antigens and adjuvants to antigen-presenting cells (APCs). Although the safety and easy production shifted the vaccine designing platforms toward the subunit vaccines, their efficacy is limited due to inefficient vaccine delivery. Nanotechnology-based vaccines, called nanovaccines, address the delivery limitations through co-delivery of antigens and adjuvants into lymphoid organs and APCs and their intracellular release, leading to cross-presentation of antigens and induction of potent anti-tumor immune responses. Although the nanovaccines, either as encapsulating agents or biomimetic nanoparticles, exert the desired anti-tumor activities, there is evidence that the mixing formulation to form nanocomplexes between antigens and adjuvants based on the electrostatic interactions provokes high levels of immune responses owing to Ags' availability and faster release. Here, we summarized the various platforms for developing cancer vaccines and the advantages of using delivery systems. The cancer nanovaccines, including nanoparticle-based and biomimetic-based nanovaccines, are discussed in detail. Finally, we focused on the nanocomplexes formation between antigens and adjuvants as promising cancer nanovaccine platforms.

Biomimetic nanoparticles drive the mechanism understanding of shear-wave elasticity stiffness in triple negative breast cancers to predict clinical treatment

In clinical practice, we noticed that triple negative breast cancer (TNBC) patients had higher shear-wave elasticity (SWE) stiffness than non-TNBC patients and a higher α-SMA expression was found in TNBC tissues than the non-TNBC tissues. Moreover, SWE stiffness also shows a clear correlation to neoadjuvant response efficiency. To elaborate this phenomenon, TNBC cell membrane-modified polylactide acid-glycolic acid (PLGA) nanoparticle was fabricated to specifically deliver artesunate to regulate SWE stiffness through inhibiting CAFs functional status. As tested in MDA-MB-231 and E0771 orthotopic tumor models, CAFs functional status inhibited by 231M-ARS@PLGA nanoparticles (231M-AP NPs) had reduced the SWE stiffness as well as attenuated hypoxia of tumor as tumor soil loosening agent which amplified the antitumor effects of paclitaxel and PD1 inhibitor. Single-cell sequencing indicated that the two main CAFs (extracellular matrix and wound healing CAFs) that produces extracellular matrix could influence the tumor SWE stiffness as well as the antitumor effect of drugs. Further, biomimetic nanoparticles inhibited CAFs function could attenuate tumor hypoxia by increasing proportion of inflammatory blood vessels and oxygen transport capacity. Therefore, our finding is fundamental for understanding the role of CAFs on affecting SWE stiffness and drugs antitumor effects, which can be further implied in the potential clinical theranostic predicting in neoadjuvant therapy efficacy through non-invasive analyzing of SWE imaging.

ROS Scavenging and inflammation-directed polydopamine nanoparticles regulate gut immunity and flora therapy in inflammatory bowel disease.

Dysfunction of the intestinal mucosal immune system and dysbiosis of the intestinal microflora can induce inflammatory bowel disease. However, drug-mediated clinical treatment remains a challenge due to its poor therapeutic efficacy and severe side effects. Herein, a ROS scavenging and inflammation-directed nanomedicine is designed and fabricated by coupling polydopamine nanoparticles with mCRAMP, an antimicrobial peptide, while wrapping macrophage membrane in the outer layer. The designed nanomedicine reduced the secretion of pro-inflammatory cytokines and elevate the expression of anti-inflammatory cytokine in vivo and in vitro inflammation models, demonstrating its significant ability of improving inflammatory responses. Importantly, the macrophage membrane encapsulated nanoparticles exhibit the obviously enhanced targeting performance in local inflamed tissues. Furthermore, the 16S rRNA sequencing of fecal microorganisms showed that probiotics increased and pathogenic bacteria were inhibited after oral delivery the nanomedicine, indicating that the designed nano platform played a significant role in optimizing intestinal microbiome. Taken together, the designed nanomedicine are not only easy to prepare and exhibit high biocompatibility, but also show the inflammatory targeting property, anti-inflammatory function and positive regulation of intestinal flora, thus providing a new idea for the intervention and treatment of colitis. STATEMENT OF SIGNIFICANCE: Inflammatory bowel disease (IBD), a chronic and intractable disease, may lead to colon cancer in severe cases without effective treatment. However, clinical drugs are largely ineffective owing to insufficient therapeutic efficacies and side effects. Herein, we constructed a biomimetic polydopamine nanoparticle for oral administration to treat the IBD by modulating mucosal immune homeostasis and optimizing intestinal microorganisms. In vitro and in vivo experiments showed that the designed nanomedicine not only exhibits the anti-inflammatory function and inflammatory targeting property but also positively regulate the gut microflora. Taken together, the designed nanomedicine combined immunoregulation and intestinal microecology modulation to significantly enhance the therapeutic effect on colitis in mice, thus providing a new approach for the clinical treatment of colitis.

Biofilm Biomimetic miR-29a Nanoparticles Inhibit Prostate Cancer Progression via Tristetraprolin/HuR-AR

Prostate cancer (PCa) occupies the second place among all male malignancies worldwide. Our study explored therapeutic mechanism of biofilm biomimetic nanoparticles encapsulating miR-29a on PCa. The expression and location of HuR and Androgen Receptor (AR) were detected by immunohistochemistry, Western blot and Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) along with analysis of cell apoptosis. After repeated extrusion of nanoparticles, cell membrane fragments were extruded into hollow spherical vesicles of 100–200 nm, which consisted of micron-scale concave disks. In prostate tissue, HuR protein was expressed in both nucleus and cytoplasm, while AR protein was mostly expressed in nucleus. miR-29a and Tristetraprolin (TTP) expressions decreased in LNCaP and DU145 (P &lt; 0.05) while the HuR level increased (P &lt; 0.05) miR-29a targeted TTP. Overexpression of miR-29a upregulated TTP and downregulated HuR (P &lt;0.05), inhibiting miR-29a expression, which decreased TTP and increased the HuR level (P &lt; 0.05). Overexpression of miR-29a inhibited cancer cell activities (P &lt; 0.05) and its inhibition inhibited apoptosis (P &lt;0.05). Biofilm biomimetic nanoparticles encapsulated miR-29a regulated TTP and HuR expression and significantly affected activities of prostate cancer cells, indicating that encapsulation of miR-29a by biofilm biomimetic nanoparticles may become a new way for prostate cancer treatment.

Application of Biomimetic Nanoparticles based on the Cell Membrane in Tumor Therapy.

Due to their unique biological functionality, nanocarriers can be designed to deliver various anti-tumor drugs in vivo, which has a wide and important application prospect in the field of tumor therapy. However, poor biosafety, short blood circulation time, and weak targeting ability still limit the application of nanoparticles in tumor therapy. In recent years, with the development of biomedicine, the biomimetic technology-based biomembrane-mediated drug delivery system is expected to achieve a breakthrough in tumor-targeted therapy due to low immunogenicity, tumor targeting, the adjustability and versatility of intelligent nanocarrier design. This paper mainly reviews the research process of different types of the cell membrane (erythrocyte membrane, cancer cell membrane, bacterial membrane, stem cell membrane, and hybrid membrane)-camouflaged nanoparticles in tumor therapy, as well as the challenges and development prospects in clinical application.

Targeted therapy for peri-prosthetic osteolysis using macrophage membrane-encapsulated human urine-derived stem cell extracellular vesicles.

Aseptic loosening of the prosthesis is a severe complication after joint replacement. It is of great practical significance and social value to discover the prevention and treatment strategies for this condition. Exosomes from urine-derived stem cells (Exos) have great potential in promoting bone repair, reconstruction, and regulating bone metabolism. However, they are easily eliminated by macrophages and incapable of targeting the osteolysis zone. In this study, based on macrophage "homing" into periprosthetic osteolysis region and cell membrane encapsulating nanotechnology, exosomes from urine-derived stem cells were encapsulated with macrophage membrane (MM) to prevent periprosthetic osteolysis. We found that macrophage membrane encapsulated urine-derived stem cell-derived exosomes (MM-Exos) can be targeted delivery to the osteolysis zone and enhance the therapeutic effectiveness of Exos, which alleviated wear particles-induced calvarial osteolysis. Furthermore, MM-Exos could provide immunological camouflage and allow the Exos to avoid phagocytosis by macrophages and stimulate cellular uptake by bone marrow-derived stem cells (BMSCs). Therefore, we demonstrated the unique ability of the macrophage membrane as a targeted transport of exosomes from urine-derived stem cells for the prevention and treatment of periprosthetic osteolysis. These biomimetic nanoparticles provided a new therapeutic exosome delivery system for preventing wear particles-induced osteolysis. STATEMENT OF SIGNIFICANCE: Macrophage membrane encapsulated urine-derived stem cell-derived exosomes (MM-Exos) can be targeted delivery to the osteolysis zone and enhance the therapeutic effect of Exos on peri‑prosthetic osteolysis prevention. MM-Exos could allow the Exos to avoid phagocytosis by macrophages and promote the uptake of Exos by BMSCs.

Biomimetic SARS-CoV-2 Spike Protein Nanoparticles.

COVID-19 is an infectious respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus contains a crucial coat protein that engages with target cells via a receptor binding domain (RBD) on its spike protein. To better study the RBD and its therapeutic opportunities, we genetically engineered a simple fusion with a thermo-responsive elastin-like polypeptide (ELP). These fusions express in Escherichia coli at a high yield in the soluble fraction and were easily purified using ELP-mediated phase separation (79 mg/L culture). Interestingly, they assembled peptide-based nanoparticles (Rh = 71.4 nm), which was attributed to oligomerization of RBDs (25.3 kDa) counterbalanced by steric stabilization by a soluble ELP (73.4 kDa). To investigate their biophysical properties, we explored the size, shape, and binding affinity for the human angiotensin-converting enzyme 2 (hACE2) and cellular uptake. Biomimetic nanoparticles such as these may enable future strategies to target the same cells, tissues, and cell-surface receptors as those harnessed by SARS-CoV-2.

Performance optimization of biomimetic ant-nest silver nanoparticle coatings for antibacterial and osseointegration of implant surfaces

Infection prevention and bone-implant integration remain major clinical challenges. Silver nanoparticle (AgNPs) bone-implant coatings have received extensive attention. Balancing the toxicity and antibacterial properties of AgNP coatings has become a significant problem. In this study, inspired by the structure of the ant-nest, a polyetherimide (PEI) coating with ant-nest structure was prepared, aiming to realize the structural modification of the AgNPs coating. AgNPs were loaded in the inner porous area of the PEI ant-nest coating, avoiding direct contact between AgNPs and cells. The nanopores on the surface of the coating ensured the orderly release of silver ions. SEM, FTIR, XPS, and XRD experiments confirmed that the PEI ant-nest coating was successfully prepared. Interestingly, in the PEI ant-nest coating, Ag+ showed a steady increase in the release trend within 28 days, and there was no early burst release phenomenon. In -vivo experiments showed a good control effect for local infection. In order to improve the osteogenic properties of the materials, 45S5 bioactive glasses (BG) were loaded to achieve further osseointegration. In general, this natural ant-nest-inspired surface modification coating for orthopedic prostheses provides a new strategy for balancing the antibacterial and toxic effects of AgNP coatings.

Rational design of peptides for biomimetic palladium nanoparticle catalysis with Suzuki and Heck coupling in ethanol

Peptide-mediated nanoparticle synthesis has been shown as an environmentally friendly way to synthesize highly reactive nanocatalysts. Previous studies have shown that peptides are capable of controlling the size and shape of metal nanoparticles made from Pd, Au, Pt, and Ag. These studies revealed that the sequence of the amino acids is critically important to optimize the performance as nanocatalysts. However, these peptide-mediated formations of nanoparticles are limited to aqueous solvents. There is a need for such optimized catalysts in organic solvents. For this, a palladium-binding peptide was modified to contain hydrophobic sequences to improve the stability and reactivity in organic solvents. Palladium nanoparticles were synthesized using the modified peptides in ethanol and used as catalysts in Suzuki and Heck coupling at a catalytic loading of 0.05 mol% at room temperature or 80 °C. The location of the hydrophobic region was found to be pivotal for increased reactivity.

Cancer cell membrane–encapsulated biomimetic nanoparticles for tumor immuno-photothermal therapy

Immune checkpoint blockade is one of the most promising approaches in cancer immunotherapy, but patient response rates are low due to low tumor immunogenicity. Herein, we proposed a biomimetic nanoparticle loaded with indocyanine green (ICG) and NLG919 (an effective IDO-1 enzyme inhibitor), which can enhance the immunogenicity of tumor through photothermal and increase the infiltration of cytotoxic T lymphocytes in tumor, thus enhancing the immunotherapy response. In a 4T1 bilateral tumor model, CFIN targeted to the tumor site, which mediated the superior photothermal effect and eliminated the primary tumor. More importantly, high temperature improved the immunogenicity of tumors and created a favorable niche for tumor-infiltrating lymphocytes (TILs) recruitment. At the same time, NLG919 was released to inhibit the activity of IDO-1 and prevented the degradation of tryptophan, thus reversing the microenvironment of immunosuppressed tumors and producing strong prevention of distant metastasis of tumors. Therefore, CFIN combines the advantages of photothermal therapy and immunotherapy to activate mature dendritic cells, initiate cytotoxic T lymphocytes, trigger the body’s innate and adaptive immune responses, eliminate primary tumors, and inhibit distal tumor growth. More importantly, CFIN can be used as a nanovaccine to provide long-term immune memory effect immunity and prevent tumor recurrence. This strategy provides a simple but promising approach for treating metastatic cancer and preventing tumors.

Membrane-camouflaged biomimetic nanoparticles as potential immunomodulatory solutions for sepsis: An overview.

Sepsis is a life-threatening organ dysfunction due to dysregulated host responses induced by infection. The presence of immune disturbance is key to the onset and development of sepsis but has remarkably limited therapeutic options. Advances in biomedical nanotechnology have provided innovative approaches to rebalancing the host immunity. In particular, the technique of membrane-coating has demonstrated remarkable improvements to therapeutic nanoparticles (NPs) in terms of tolerance and stability while also improving their biomimetic performance for immunomodulatory purposes. This development has led to the emergence of using cell-membrane-based biomimetic NPs in treating sepsis-associated immunologic derangements. In this minireview, we present an overview of the recent advances in membrane-camouflaged biomimetic NPs, highlighting their multifaceted immunomodulatory effects in sepsis such as anti-infection, vaccination, inflammation control, reversing of immunosuppression, and targeted delivery of immunomodulatory agents.

A Novel Ultrasound‐Responsive Biomimetic Nanoparticle for Targeted Delivery and Controlled Release of Nitric Oxide to Attenuate Myocardial Ischemia Reperfusion Injury

Targeted and controlled nitric oxide (NO) release is critical due to an extremely short half life and low bioavailability for treating cardiovascular diseases. To address this challenge, various sustained‐release precursors and NO donors activated by light, enzyme, or pH are developed. However, their efficacy is limited by the deep location and rapid blood flow of the heart. Herein, a platelet membrane‐coated nanoparticle (B‐P@PLT) is designed with a polymeric core loaded with BNN6, an ultrasound‐responsive NO donor, for the targeted treatment of myocardial ischemia reperfusion injury (MIRI). B‐P@PLT can specifically target the ischemic myocardium and release NO during ultrasound (US) irradiation, thereby increasing the local concentration of NO. B‐P@PLT + US shows promising results in promoting angiogenesis, reducing reactive oxygen species production, protecting cardiomyocytes both in vitro and in vivo, and ultimately decreasing cardiac injury and improving heart function in MIRI mice. These findings demonstrate a simple and noninvasive strategy for targeted delivery and controlled release of NO, highlighting its potential therapeutic application in MIRI.