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This work developed a self-anticancer nanocarrier based on bioactive poly(p-coumaric acid) for the effective delivery of docetaxel, achieving enhanced therapeutic efficacy against colon cancer.

Foodborne biomaterials, derived from diets, comprise selfassembled collections of many micro- or nanoscale units with abundant nutrients and active substances. In this study, soybean milk (SBM) was selected as a tissue engineering product for simple and feasible wound repair. SBM is a common drink prepared from soybeans and is rich in soy protein, soy isoflavones, and other bioactive components. Thus, SBM has substantial potential for antioxidation and tissue remodeling. Here, the multifunctional effect of SBM as a bioactive coating for promoting wound healing was studied. The results showed that SBM has good biocompatibility and biological activity. It efficiently scavenges intracellular reactive oxygen species, significantly enhances epithelial cell migration, and improves angiogenesis, thereby accelerating tissue remodeling. The results of animal experiments further confirmed that the SBM-bioinspired coating has promising applications for cutaneous wound regeneration.

The last few decades have witnessed the emergence of a very large variety of engineered nanomaterials. However, it is far from to meet the growing clinical demand. Actually, nature itself is an excellent nanotechnologist, and provides us with a range of wonderful materials, from inorganic particles found in non-life bodies to biofilms, like platelets, erythrocyte membranes, produced by many bacteria or cells. These nanomaterials are entirely natural, and not surprisingly, there is a growing interest in the development of natural nanoproducts. Native components-inspired biomaterials have gained considerable attention owing to their safety and functions. In this study, egg white was developed as drug carrier to load PTX by a green and simple one-pot method, and systematic characterization was completed. The results indicated that PTX@EW NPs possess excellent biocompatibility, enhanced tumor targeting capability, effectively reducing the toxic side effects of PTX. The obviously enhanced antitumor effect further confirmed EW was a highly prospective biomaterial in the nano-carrier industry.

Using biocompatible polymers with potential therapeutic activity is an appealing strategy for the development of new functional drug carriers. In this study, we report the synthesis of therapeutic poly(

Effective cancer treatment puts high demands for cancer theranostics. For cancer diagnostics, optical coherence tomography (OCT) technology (including photothermal optical coherence tomography (PT-OCT)) has been widely investigated since it induces changes in optical phase transitions in tissue through environmental changes (such as temperature change for PT-OCT). In this report, redox responsive nanoparticle encapsulating black phosphorus quantum dots was developed as a robust PT-OCT agent. Briefly, black phosphorus quantum dots (BPQDs) are incorporated into cysteine-based poly-(disulfide amide) (Cys-PDSA) to form stable and biodegradable nanoagent. The excellent photothermal feature allows BPQD/Cys-PDSA nanoparticles (NPs) as a novel contrast agent for high-resolution PT-OCT bioimaging. The Cys-PDSA can rapidly respond to glutathione and effectively release BPQDs and drugs in vitro and in vivo. And the obtained NPs exhibit excellent near-infrared (NIR) photothermal transduction efficiency and drug delivery capacity that can serve as novel therapeutic platform, with very low chemo drug dosage and side effects. Both of the polymer and BPQD are degradable, indicating this platform is a rare PT-OCT agent that is completely biodegradable. Overall, our research highlights a biodegradable and biocompatible black phosphorus-based nanoagent for both cancer diagnosis and therapy., Graphical abstract Image 1, Highlights • Black phosphorus based nanoplatform, the first PT-OCT nanoplatform could be completely degraded in vitro and in vivo. • Black phosphorus quantum dots and chemo drugs have been successfully encapsulated into redox responsive nanoparticles. • Very low dose of PTX (such as 1 mg/kg, 1/10 of normal dose) could achieve excellent therapeutic performance for this platform.

Cyclodextrins (CDs) are widely employed in biomedical applications because of their unique structures. Various biomedical applications can be achieved in a spatiotemporally controlled manner by integrating the host-guest chemistry of CDs with stimuli-responsive functions. In this review, we summarize the recent advances in stimuli-responsive supramolecular assemblies based on the host-guest chemistry of CDs. The stimuli considered in this review include endogenous (pH, redox, and enzymes) and exogenous stimuli (light, temperature, and magnetic field). We mainly discuss the mechanisms of the stimuli-responsive ability and present typical designs of the corresponding supramolecular assemblies for drug delivery and other potential biomedical applications. The limitations and perspectives of CD-based stimuli-responsive supramolecular assemblies are discussed to further promote the translation of laboratory products into clinical applications.

In recent years, peptide/protein drugs have attracted considerable attention owing to their superior targeting and therapeutic effect and fewer side effects compared with chemical drugs. Oral administration modality with enhanced patient compliance is increasingly being recognized as an ideal route for peptide/protein delivery. However, the limited permeation efficiency and low oral bioavailability of peptide/protein drugs significantly hinder therapeutic advances. To address these problems, various nano and microscale delivery platforms have been developed, which offer significant advantages in oral peptide/protein delivery. In this review, we briefly introduce the transport mechanisms of oral peptide/protein delivery and the primary barriers to this delivery process. We also highlight the recent advances in various nano and microscale delivery platforms designed for oral peptide/protein delivery. We then summarize the existing strategies used in these delivery platforms to improve the oral bioavailability and permeation efficiency of peptide/protein therapeutics. Finally, we discuss the major challenges faced when nano and microscale systems are used for oral peptide/protein delivery. This review is expected to provide critical insight into the design and development of oral peptide/protein delivery systems with significant therapeutic advances.

The use of cisplatin is restricted by systemic toxicity and drug resistance. Supramolecular nano-drug delivery systems involving drugs as building blocks circumvent these limitations promisingly. Herein, we describe a novel supramolecular system [Pt(IV)-SSNPs] based on poly(β-cyclodextrin), which was synthesized for efficient loading of adamantly-functionalized platinum(IV) prodrug [Pt(IV)-ADA

Chemotherapy drugs have been known as the mainstay of cancer treatment; however, they have inevitable side effects when used in isolation. Drug-loaded nanosystems represent a breakthrough drug delivery platform that enhances the treatment index of chemotherapy in cancer treatment; further, it compensates for the deficiency of body toxicity and significantly enhances antitumor effects. Given that designing biosafe nanodrugs requires nontoxicity of carriers, novel polymers, synthesized from natural products, with good biocompatibility and biodegradation are the preferred drug carriers. Ferulic acid (FA) derived from plants can be chemically modified to form poly(ferulic acid) (PFA) with reassuring biosafety. PFA-loading doxorubicin (DOX) was properly self-assembled into stable PFA@DOX nanoparticles (NPs), which released payloads continuously under slightly acidic conditions in vitro, ensuring effective drug delivery in acidic tumor microenvironments. In vivo antitumor therapy showed that the PFA nanocarriers could promote accumulation and retention at the tumor site for superior tumor suppression, while the PFA@DOX NPs reduced the physical toxicity of free DOX, thereby, improving safety. Therefore, such drug-loaded NPs can exert considerable influence over an antitumor action for potential clinical translation in the future.

Intratumoral delivery of chemotherapeutic agents may permit the localization of drugs in tumors, decrease nonspecific targeting and increase efficacy. The pH-responsive peptide hydrogel is considered a suitable carrier for chemotherapeutics via intratumoral injection. Thus, a study was carried out to develop a paclitaxel (PTX) drug delivery system using a pH-responsive FER-8 peptide hydrogel for tumor targeting. The pH-sensitive hydrogel system was characterized for loading capacity, acid sensitivity, structure, rheology, morphology, drug release, in vitro cytotoxicity and in vivo efficacy in H22 tumor-bearing mice. The stable FER-8 peptide hydrogel with high drug-loading capacity was formed at pH 7.4 by the self-assembly of peptide, whereas higher degradation was observed at an acidic pH. Circular dichroism and rheology confirmed the suitable meshwork structure and enhanced mechanical properties of the hydrogel. The FER-8 peptide hydrogel fibers were found to have an average size less than 500 nm at pH 7.4, which was confirmed by TEM and DLS analysis. Sustained release of PTX at pH 5.5 was observed for the FER-8 peptide hydrogel (HG-PTX) for almost 1 week. In vitro cytotoxicity studies indicated that the FER-8 peptide hydrogel increased the drug accumulation in HepG2 cells and effectively inhibited the growth of HepG2 tumor cells compared with free drugs. Furthermore, in vivo studies using H22-bearing mice indicated that the paclitaxel-loaded FER-8 peptide hydrogel significantly increased the amount of drugs in tumor tissues and showed prolonged retention (96 hours) at the tumor site by intratumoral injection. The in vivo anti-tumor studies confirmed the pH-sensitive properties of HG-PTX, which allowed the drug to be triggered by the acidic pH environment at tumor sites, provided sustained delivery of the drug and enhanced tumor inhibition. In conclusion, HG-PTX provides an attractive strategy and potential vehicle for efficient anti-cancer drug delivery. The carrier can enhance tumor targeting, prolong retention, reduce systemic side effects and increase the accumulation of drugs at the tumor site.

The applications of nanoparticulate drug delivery have received abundant interest in the field of cancer diagnosis and treatment. By virtue of their unique features and design, nanomedicines have made remarkable progress in eliminating dreadful tumors. Research in cancer nanomedicine has spanned multitudes of drug delivery systems that possess high tumor targeting ability, sensitivity towards tumor microenvironments and improved efficacy. Various nanocarriers have been developed and approved for anti-tumor drug targeting. These nanocarriers, i.e., liposomes, micelles, nanotubes, dendrimers and peptides, offer a wide range of advantages, such as high selectivity, multi-functionality, specificity, biocompatibility and precise control of drug release. Nanomedicines based on self-assembled peptide carrier systems have been developed in recent years for cancer targeting. Self-assembled peptides have tremendous properties of forming targeted drug delivery vehicles such as nanohydrogels with unique features and functionality. In this review article, we discuss some developments in cancer nanomedicine. We present a diverse range of nanotargeted drug-delivery systems.

Intracellular delivery of messenger RNA (mRNA)-based cancer vaccine has shown great potential to elicit antitumor immunity. To achieve robust antitumor efficacy, mRNA encoding tumor antigens needs to be efficiently delivered and translated in dendritic cells with concurrent innate immune stimulation to promote antigen presentation. Here, by screening a group of cationic lipid-like materials, we developed a minimalist nanovaccine with C1 lipid nanoparticle (LNP) that could efficiently deliver mRNA in antigen presenting cells with simultaneous Toll-like receptor 4 (TLR4) activation and induced robust T cell activation. The C1 nanovaccine entered cells via phagocytosis and showed efficient mRNA-encoded antigen expression and presentation. Furthermore, the C1 lipid nanoparticle itself induced the expression of inflammatory cytokines such as IL-12 via stimulating TLR4 signal pathway in dendritic cells. Importantly, the C1 mRNA nanovaccine exhibited significant antitumor efficacy in both tumor prevention and therapeutic vaccine settings. Overall, our work presents a C1 LNP-based mRNA cancer nanovaccine with efficient antigen expression as well as self-adjuvant property, which may provide a platform for developing cancer immunotherapy for a wide range of tumor types.

The adaptation of osteosarcoma cells to therapeutic pressure impedes the efficacy of chemotherapy for osteosarcoma. However, the characteristics and cellular organization of therapy-resistant cells in osteosarcoma tumors remain elusive. Here, we utilized single-cell transcriptomics to systematically map the cell-type-specific gene expression in a chemotherapy-resistant osteosarcoma tumor. Our data demonstrated the VEGFR2-JMJD3-abundant subsets as quiescent stem-like cells, thereby establishing the hierarchy of therapy-resistant actively cycling progenitor pools (JMJD3-abundant) in osteosarcoma. VEGFR2 inhibitor and JMJD3 inhibitor synergistically impeded osteosarcoma cell propagation and tumor growth. Although osteosarcoma cells are predisposed to apoptosis induced by the synergistic therapy through activation of the CHOP pro-apoptotic factor via the endoplasmic reticulum (ER) stress, the stem-like/progenitor cells exhibit an adaptive response, leading to their survival. Reduction in cellular glutathione levels in stem-like/progenitor cells caused by the treatment with a glutathione synthesis inhibitor increases ER stress-induced apoptosis. Importantly, the marked therapeutic improvement of synergistic therapy against stem-like/progenitor cells was achieved by using glutathione-scavenging nanoparticles, which can load and release the drug pair effectively. Overall, our study provides a framework for understanding glutathione signaling as one of the therapeutic vulnerabilities of stem-like/progenitor cells. Broadly, these findings revealed a promising arsenal by encapsulating glutathione-scavenging nanoparticles with co-targeting VEGFR2 and JMJD3 to eradicate chemotherapy-resistant osteosarcoma.

An uncontrolled hemorrhage can easily lead to death during surgery and military operations. Despite the significant advances in hemostatic research, there is still an urgent and increasing need for safer and more effective hemostatic materials. Recently, nanotechnologies have been receiving increasing interest owing to their unique advantages and have been propelling the developement of hemostatic materials. This review summarizes the fundamentals of hemostasis and emphasizes the recent developments regarding hemorrhage-related hemostatic nanotechnologies. In terms of external accessible hemorrhage management, natural and synthetic polymers and inorganic components that have been used in traditional hemostats provide novel nanoscale solutions. Regarding internal noncompressible hemorrhage management, current research endeavors are dedicated to the development of substitutes for blood components, and nanoformulated hemostatic drugs. This review also briefly discusses the main and persistent problems of hemostatic nanomaterials, including safety concerns and clinical translation challenges. This review is hoped to provide critical insight into hemostatic nanomaterial development.

In this study, a novel protein–polymer conjugate, D-α-tocopheryl polyethylene glycol succinate modified reduced bovine serum albumin (TPGS–Re-BSA, TRB), was synthesized for lipophilic anticancer drug delivery, and its unique ability to overcome drug resistance was explored. This conjugate was extensively characterized for its chemical structure, average molecular weight, secondary structure, degree of substitution, hydrophobicity, particle size and zeta potential. PTX-loaded nanoparticles (NPs) with diameters of 170–370 nm and drug loading efficiency of up to 13.62% were successfully prepared by the dialysis method. These drug-loaded NPs were found to exhibit a sustained release of PTX at pH 7.4, 6.5 and 5.5. Moreover, great anti-tumor activity in drug sensitive MCF-7 cells was observed in the in vitro anti-tumor studies. In particular, enhanced cytotoxicity and PTX-induced apoptosis were observed in the drug-resistant MCF-7/ADR cells compared to the Taxol and PTX-loaded BSA NPs. This could be attributed to the significant inhibition of P-gp activity and reduced ATP levels due to the presence of TRB NPs. Lastly, in vivo tumor inhibition assay verified the higher efficacy of TRB NPs. Overall, the results suggest that this TRB NPs could provide an effective carrier system for the delivery of anticancer agents.

Colorectal cancer (CRC) is the third-most common malignant tumour and is associated with high morbidity and mortality worldwide. This review summarizes the recent progress in the development of polymeric nanoparticle systems for colon cancer therapy.

Tofu not only is a delicious vegetarian food, but also shows potential biomedical applications for its high protein content and typical porous scaffold structure. Herein, two kinds of porous soybean scaffolds were developed, the first based on the traditional tofu manufacturing processes, the second modified via covalent crosslinking. The morphology, physicochemical properties and biocompatibility in vitro and in vivo were systematically investigated. A similar porous micromorphology was observed in both the tofu scaffolds and crosslinked soybean protein scaffolds. Both scaffolds exhibited good cell proliferation and cellular adherence. No obvious inflammatory response was observed after subcutaneous implantation tests for either material. These results demonstrated that the tofu scaffolds or soybean protein scaffolds fabricated by tofu processing have potential as new food-source biomaterials in tissue engineering applications.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignant cancer with complex genomic variations, and no targetable genomic lesions have been found yet. Super‐enhancers (SEs) have been found to contribute to the continuous and robust oncogenic transcription. Here, histone H3 lysine 27 acetylation (H3K27ac) is profiled in PDAC cell lines to establish SE landscapes. Concurrently, it is also shown that PDAC is vulnerable to the perturbation of the SE complex using bromodomain‐containing protein 4 (BRD4) inhibitor, JQ1, synergized with cyclin‐dependent kinase 7 (CDK7) inhibitor, THZ1. Formulations of hydrophobic l‐phenylalanine‐poly (ester amide) nanoparticles (NPs) with high drug loading of JQ1 and THZ1 (J/T@8P4s) are further designed and developed. J/T@8P4s is assessed for size, encapsulation efficiency, morphology, drug release profiles, and drug uptake in vitro. Compared to conventional free drug formulation, the nanodelivery system dramatically reduces the hepatotoxicity while significantly enhancing the tumor inhibition effects and the bioavailability of incorporated JQ1 and THZ1 at equal doses in a Gemcitabine‐resistant PDAC patient‐derived xenograft (PDX) model. Overall, the present study demonstrates that the J/T@8P4s can be a promising therapeutic treatment against the PDAC via suppression of SE‐associated oncogenic transcription, and provides a strategy utilizing NPs to assist the drug delivery targeting SEs., The H3K27ac profile defines super‐enhancer (SE) landscapes in pancreatic ductal adenocarcinoma (PDAC). PDAC is vulnerable to the perturbation of the SE complex using JQ1 synergized with THZ1. Importantly, the nanodelivery system significantly enhances the tumor inhibition effects of combination therapy on a Gemcitabine‐resistant PDAC patient‐derived xenograft model.

Type 1 diabetes mellitus (T1DM) is a chronic metabolic disease caused by the destruction of pancreatic β-cells in response to autoimmune reactions. Shapiro et al. conducted novel islet transplantation with a glucocorticoid-free immunosuppressive agent in 2000 and achieved great success; since then, islet transplantation has been increasingly regarded as a promising strategy for the curative treatment of T1DM. However, many unavoidable challenges, such as a lack of donors, poor revascularization, blood-mediated inflammatory reactions, hypoxia, and side effects caused by immunosuppression have severely hindered the widespread application of islet transplantation in clinics. Biomaterial-based encapsulation and delivery strategies are proposed for overcoming these obstacles, and have demonstrated remarkable improvements in islet transplantation outcomes. Herein, the major problems faced by islet transplantation are summarized and updated biomaterial-based strategies for islet transplantation, including islet encapsulation across different scales, delivery of stem cell-derived beta cells, co-delivery of islets with accessory cells and immunomodulatory molecules are highlighted.

Xuejun Qiu,1 Xinru You,2 Xing Chen,2 Haolin Chen,1 Arvind Dhinakar,3 Songhao Liu,1 Zhouyi Guo,1 Jun Wu,2,4 Zhiming Liu1 1SATCM Third Grade Laboratory of Chinese Medicine and Photonics Technology, College of Biophotonics, South China Normal University, 2Guangdong Provincial Key Laboratory of Sensor Technology and Biomedical Instrument, School of Engineering, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China; 3Faculty of Engineering, University of Waterloo, Waterloo, ON, Canada; 4Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China Abstract: The rapid development of near-infrared surface-enhanced Raman scattering (NIR SERS) imaging technology has attracted strong interest from scientists and clinicians due to its narrow spectral bandwidth, low background interference, and deep imaging depth. In this report, the graphene oxide (GO)-wrapped gold nanorods (GO@GNRs) were developed as a smart and robust nanoplatform for ultrafast NIR SERS bioimaging. The fabricated GO@GNRs could efficiently load various NIR probes, and the in vitro evaluation indicated that the nanoplatform could exhibit a higher NIR SERS activity in comparison with traditional gold nanostructures. The GOs were prepared by directly pyrolyzing citric acid for greater convenience, and GO@GNRs were fabricated via a facile synthesis strategy. Higher NIR SERS activity, facile synthesis method, excellent biocompatibility, and superb stability make the GO@GNRs/probe complex promising nanoprobes for NIR SERS-based bioimaging applications. Keywords: gold nanorods, graphene oxide, near-infrared bioimaging, surface-enhanced Raman scattering

As a significant part of molecular-targeted therapies, small-molecule agents (SMAs) have been increasingly used for cancer treatment. Nevertheless, most SMAs are currently administered orally due to their poor solubility, resulting in a low bioavailability and unavoidable side effects. Herein, we proposed a promising SMA delivery strategy using a biocompatible and redox-responsive nanoparticle (NP) delivery system to improve their bioavailability, alleviate side effects and enhance therapeutic performance. To demonstrate the feasibility of this strategy, a type of cysteine-based hydrophobic polymer was employed to construct a redox-sensitive nanoplatform for the delivery of various hydrophobic oral SMAs. These SMA-loaded nanoparticles (SMA-NPs) all have a small particle size and good drug-loading capacity. Particularly, lapatinib-loaded nanoparticles (LAP-NPs) with a minimal particle size (79.71 nm) and an optimal drug-loading capacity (12.5%) were utilized as a model to systemically explore the in vitro and in vivo anticancer potential of SMA-NPs. As expected, the LAP-NPs exhibited rapid redox-responsive drug release, enhanced in vitro cytotoxicity and cell apoptosis, and demonstrated notable anti-metastasis ability and desirable intracellular localization. Additionally, the in vivo results demonstrated the preferential accumulation of LAP-NPs in tumor tissues and the significant suppression of tumor growth. Therefore, the generated SMA-NP delivery system shows great SMA delivery potential for advanced molecular-targeted therapies.

Traditional prostate cancer therapy and especially chemotherapy has faced many challenges. Low accumulation levels, rapid clearance or drug resistance at the tumor site have been central to why the effect of chemotherapy drugs has declined. Applications of nanotechnology to biomedicine have enabled the development of nanoparticle therapeutic carriers suited for the delivery of chemotherapeutics in cancer therapy. This review describes the current nature of nanoparticle therapeutic carriers for prostate cancer. It describes typical nanocarriers commonly used for the delivery of chemotherapy or for imaging examination. Targeting strategies and related influencing factors are investigated to find ways of enhancing treatment effects of nanoparticles. The overall purpose of this review is to further understanding and to offer recommendations on the design and development of therapeutic nanoparticles for prostate cancer.

In this study, for effective oral cancer therapy, a new targeted and ROS-triggered drug delivery nanoplatform was developed from the RGD-PEG-TK-PLGA polymer, in which the ROS-responsive TK containing linker was connected with PEG and PLGA. RGD in the drug delivery system (DDS) presented here was used to target cancer cells. This new nanoplatform shows high stability, good targeting ability, excellent ROS sensitivity and excellent biocompatibility. Loaded with DOX and alpha-TOS, the formulated nanoparticles (NPs) demonstrate much better cellular uptake efficiency and higher inhibition performance towards the oral tongue Cal27 cancer cell line. In vivo anticancer evaluation indicates that DOX and alpha-TOS loaded RGD-PEG-TK-PLGA NPs have no toxicity to mice and showed significantly improved therapeutic efficacy against tumors. Therefore, this polymeric NP platform presents great potential as a new DDS for oral cancer chemotherapy.

Ischemia-reperfusion (I/R) is a major cause of acute kidney injury (AKI), which is associated with unacceptably high mortality rates in ICU. This research was designed to explore the therapeutic effect of BAPTA-AM (1,2-Bis(2-aminophenoxy) ethane-N,N,N,N-tetraacetic acid tetrakis(acetoxymethyl ester)) nanoparticle (BA-N) on AKI. BA-N was developed by liposome strategy and characterized by standard methods. The rat model was selected and the rats were randomly allocated into four groups: (1) Normal group; (2) Sham-operated group; (3) Model group (I/R + NS); (4) BA-N treatment group (I/R + BA-N). AKI model was established via clipping the bilateral renal artery with a microvascular clamp for 45 min. After reperfusion, serum cystatin C (Cys C), creatinine (Cr), blood urea nitrogen (BUN), lactate dehydrogenase (LDH) and caspase 3 levels were determined for the assessment of renal function. Kidney samples were then collected for the measurement of renal malondialdehyde (MDA) level and superoxide dismutase (SOD) activity. The assays of histological examination, ELISA, immunohistochemistry, western blot, TUNEL and RT-PCR were utilized for the detection of apoptosis. The results demonstrated that AKI model caused a significant decreasing in SOD activity, accompanied by a remarkable increase in Cys C, Cr, BUN, LDH, MDA, caspase 3 and cytochrome c (Cyt C) level, compared to the control group. BA-N (100 μg/kg i.v.) significantly improved renal function and histopathological appearance, restored MDA level and SOD activity, decreased Bax/Bcl-2 ratio, caspase 3 activity, Cyt C release and TUNEL positive apoptotic cells. Our studies indicated that BA-N plays a renal-protective role, probably through antiapoptotic and antioxidant mechanisms. BA-N may regulate mitochondria pathway via decreasing Bax/Bcl-2 ratio, inhibiting caspase 3 expression and Cyt C release. Overall, BA-N may have potentials as an anti-AKI drug.

Many different types of polycations have been vigorously studied for nucleic acid delivery, but a systematical investigation of the structure–property relationships of polycations for nucleic acid delivery is still lacking. In this study, a new library of biodegradable and biocompatible arginine-based poly(ester amide) (Arg-PEA) biomaterials was designed and synthesized with a tunable structure for such a comprehensive structure–property research. Nanoparticle (NP) complexes were formed through the electrostatic interactions between the polycationic Arg-PEAs and anionic nucleic acids. The following structure effects of the Arg-PEAs on the transfection efficiency of nucleic acids were investigated: 1) the linker/spacer length (length effect and odd–even effect); 2) salt type of arginine; 3) the side chain; 4) chain stiffness; 5) molecular weight (MW). The data obtained revealed that a slight change in the Arg-PEA structure could finely tune its physicochemical property such as hydrophobicity, and this could subsequently affect the nanoparticle size and zeta potential, which, in turn, regulate the transfection efficiency and silencing outcomes. A further study of the Arg-PEA/CpG oligodeoxynucleotide NP complexes indicated that the polymer structure could precisily regulate the immune response of CpG, thus providing a new potential nano-immunotherapy strategy. The in vitro data have further confirmed that the Arg-PEA NPs showed a satisfactory delivery performance for a variety of nucleic acids. Therefore, the data from the current study provide comprehensive information about the Arg-PEA structure–transfection property relationship; the tunable property of the library of Arg-PEA biomaterials can be one of the promising candidates for nucleic acid delivery and other biomedical applications. Statement of Significance Polycations have being intensive utilized for nucleic acid delivery. However, there has not been elucidated about the relationship between polycation’s structure and the physicochemical properties/biological function. In this timely report, an arginine based poly(ester amide) (Arg-PEA) library was prepared with finely tunable structure to systematically investigate the structure–property relationships of polycations for nucleic acid delivery. The results revealed that slight change of Arg-PEA structure could finely tune the physicochemical property (such as hydrophobicity), which subsequently affect the size and zeta potential of Arg-PEA/nucleic acid nanoparticles(NPs), and finally regulate the resulting transfection or silencing outcomes. Further study of Arg-PEA/CpG NPs indicated that the polymer structure could precisely regulate immuno response of CpG, providing new potential nano-immunotherapy strategy. In vitro evaluations confirmed that the NPs showed satisfied delivery performance for a variety types of nucleic acids. Therefore, these studies provide comprehensive information of Arg-PEA structure–property relationship, and the tunable properties of Arg-PEAs make them promising candidates for nucleic acid delivery and other biomedical applications. Overall, we have shown enough significance and novelty in terms of nucleic acid delivery, biomaterials, pharmaceutical science and nanomedicine.