Search

Nanoparticle-based cancer immunotherapy has shown promising therapeutic potential in clinical settings. However, current research mainly uses nanoparticles as delivery vehicles but overlooks their potential to directly modulate immune responses. Inspired by the endogenous endoplasmic reticulum (ER) stress caused by unfolded/misfolded proteins, we present a rationally designed immunogenic cell death (ICD) inducer named NanoICD, which is a nanoparticle engineered for ER targeting and retention. By carefully controlling surface composition and properties, we have obtained NanoICD that can effectively accumulate in the ER, induce ER stress, and activate ICD-associated immune responses. In addition, NanoICD is generally applicable to various proteins and enzymes to further enhance the immunomodulatory capacity, exemplified by encapsulating catalase (CAT) to obtain NanoICD/CAT, effectively alleviated immunosuppressive tumor microenvironment and induced robust antitumor immune responses in 4T1-bearing mice. This work demonstrates engineered nanostructures' potential to autonomously regulate biological processes and provides insights into the development of advanced nanomedicines for cancer treatment.

Bacterial sepsis is a life-threatening condition caused by bacteria entering the bloodstream and triggering an immune response, underscoring the importance of early recognition and prompt treatment. Nanomedicine holds promise for addressing sepsis through improved diagnostics, nanoparticle biosensors for detection and imaging, enhanced antibiotic delivery, combating resistance, and immune modulation. However, challenges remain in ensuring safety, regulatory compliance, scalability, and cost-effectiveness before clinical implementation. Further research is needed to optimize design, efficacy, safety, and regulatory strategies for effective utilization of nanomedicines in bacterial sepsis diagnosis and treatment. This review highlights the significant potential of nanomedicines, including improved drug delivery, enhanced diagnostics, and immunomodulation for bacterial sepsis. It also emphasizes the need for further research to optimize design, efficacy, safety profiles, and address regulatory challenges to facilitate clinical translation.

The vagina has been regarded as a crucial route for drug delivery. Despite the wide range of available vaginal dosage forms for vaginal infection control, poor drug absorptivity remains a significant challenge due to various biological barriers in the vagina, such as mucus, epithelium, immune systems, and others. To overcome these barriers, different types of vaginal drug delivery systems (VDDSs), with outstanding mucoadhesive, mucus-penetrating properties, have been designed to enhance the absorptivity of vagina-administered agents in the past decades. In this Review, we introduce a general understanding of vaginal administration, its biological barriers, the commonly used VDDSs, such as nanoparticles and hydrogels, and their applications in controlling microbe-associated vaginal infections. Additionally, further challenges and concerns regarding the design of VDDSs will be discussed.

Drug combination provides an efficient pathway to combat drug resistance in bacteria and bacterial biofilms. However, the facile methodology to construct the drug combinations and their applications in nanocomposites is still lacking. Here the two-tailed antimicrobial amphiphiles (T 2 A 2 ) composed of nitric oxide (NO)-donor (diethylenetriamine NONOate, DN) and various natural aldehydes are reported. T 2 A 2 self-assemble into nanoparticles due to their amphiphilic nature, with remarkably low critical aggregation concentration. The representative cinnamaldehyde (Cin)-derived T 2 A 2 (Cin-T 2 A 2 ) assemblies demonstrate excellent bactericidal efficacy, notably higher than free Cin and free DN. Cin-T 2 A 2 assemblies kill multidrug-resistant staphylococci and eradicate their biofilms via multiple mechanisms, as proved by mechanism studies, molecular dynamics simulations, proteomics, and metabolomics. Furthermore, Cin-T 2 A 2 assemblies rapidly eradicate bacteria and alleviate inflammation in the subsequent murine infection models. Together, the Cin-T 2 A 2 assemblies may provide an efficient, non-antibiotic alternative in combating the ever-increasing threat of drug-resistant bacteria and their biofilms., (© 2023 Wiley-VCH GmbH.)

Prodrug nanoassemblies combine the advantages of prodrug and nanomedicines, offering great potential in targeting the lesion sites and specific on-demand drug release, maximizing the therapeutic performance while minimizing their side effects. However, there is still lacking a facile pathway to prepare the lipid prodrug nanoassemblies (LPNAs). Herein, we report the LPNAs via the dynamic covalent boronate between catechol and boronic acid. The resulting LPNAs possess properties like drug loading in a dynamic covalent manner, charge reversal in an acidic microenvironment, and specific drug release at an acidic and/or oxidative microenvironment. Our methodology enables the encapsulation and delivery of three model drugs: ciprofloxacin, bortezomib, and miconazole. Moreover, the LPNAs are often more efficient in eradicating pathogens or cancer cells than their free counterparts, both in vitro and in vivo . Together, our LPNAs with intriguing properties may boost the development of drug delivery and facilitate their clinical applications.

Therapeutic cancer vaccines, which are designed to amplify tumor-specific T cell responses, have been envisioned as one of the most powerful tools for effective cancer immunotherapy. However, increasing the potency, quality and durability of the vaccine response remains a big challenge. In recent years, materials-based delivery systems focusing on the co-delivery of antigens and adjuvants to enhance cancer vaccination therapy have attracted increasing interest. Among various materials, polymeric nanoparticles (NPs) with different physicochemical properties which can incorporate multiple immunological cues are of great interest. In this review, the recent progress in the design and construction of both ex vivo subunit and in situ cancer vaccines using polymeric NPs is summarized. Especially, we will focus on how these NPs improve the adjuvanticity of vaccines. The design principles of polymeric NPs for ex vivo subunit cancer vaccines and in situ cancer vaccination are also discussed. Finally, we want to briefly discuss molecular chaperones in cancer immunity and the applications of our unique self-assembly mixed shell polymeric micelle-based nanochaperones for cancer vaccines.

Biological barriers significantly limit the delivery efficiency of drug delivery systems, resulting in undesired therapeutic effects. When designing a delivery system with optimized penetration behavior across the biological barriers, mechanical properties, such as deformability, are emerging as important parameters that need to be considered, although they are usually neglected in current research. Herein, a liquid core nanoparticle (LCN) composed of a polymer-encapsulated edible oil droplet is demonstrated. Owing to the unique structure in which the liquid oil core is encapsulated by a layer of highly hydrophilic and cross-linked polymer, the LCN exhibits high mechanical softness, making it deformable under external forces. With high deformability, LCNs can effectively penetrate through several important biological barriers including deep tumor tissue, blood-brain barriers, mucus layers, and bacterial biofilms. Moreover, the potential of the LCN as a drug delivery system is also demonstrated by the loading and release of several clinical drugs. With the capability of penetrating biological barriers and delivering drugs, LCN provides a potential platform for disease treatments, particularly for those suffering from inadequate drug penetration., (© 2022 Wiley-VCH GmbH.)

Photothermal therapy (PTT) has attracted extensive attention in disease treatments. However, conventional photothermal systems do not possess a temperature-control mechanism, which poses a serious risk to healthy tissues and/or organs due to inevitable thermal damage. Herein, a smart photothermal nanosystem with an intrinsic temperature-control mechanism for thermostatic treatment of bacterial infections is reported. The smart photothermal nanosystem is constructed by loading a thermochromic material into a hollow-structured silica nanocarrier, in which the thermochromic material is composed of naturally occurring phase-change materials (PCMs), a proton-responsive spirolactone, and a proton source. The resulting nanosystem shows strong near-infrared (NIR) absorption and efficient photothermal conversion in solid PCMs but becomes NIR-transparent when PCMs are melted upon NIR irradiation. Such an attractive feature can precisely regulate the photothermal equilibrium temperature to the melting point of PCMs, regardless of the variation in external experimental parameters. In contrast to conventional PTT with severe thermal damage, the reported smart photothermal nanosystem provides an internal protection mechanism on healthy tissues and/or organs, which remarkably accelerates the recovery of bacteria-infected wounds. The smart photothermal nanosystem is a versatile PTT platform, holding great promise in the safe and efficient treatment of bacterial infections and multimodality synergistic therapy., (© 2022 Wiley-VCH GmbH.)

Rationale: In combination chemotherapy, the molar ratio of drugs is a critical parameter that determines the synergistic effects. However, most co-delivery vectors are incapable of maintaining the optimal molar ratio of drugs throughout the delivery process. Herein, a calixarene-modified albumin (CaMA), which can co-deliver multiple drugs with precise control of the drug ratio, is presented. Methods: CaMA was prepared by chemically conjugating multiple sulfonate azocalix[4]arenes (SAC4A) onto the surface of bovine serum albumin (BSA). The precise drug loading and synchronous drug release were measured using fluorescence spectroscopy. Mouse tumor cell 4T1 and 4T1-bearing mice were used to evaluate the combined effects of mitomycin C (MMC) and doxorubicin (DOX) in vitro and in vivo . Results: With multiple hypoxia-responsive calixarenes conjugated onto a single albumin molecule, CaMA achieved precise drug loading and synchronous release of multiple drugs into the tumor microenvironment. This unique drug loading and release mechanism ensures that CaMA maintains the drug ratio from the initial drug loading to the release site, providing a solid foundation for multi-drug combination therapy with the goal of achieving predictable therapeutic outcomes in vivo . The delivery of the model drug combination MMC and DOX at a prescreened ratio via CaMA achieved significantly enhanced tumor suppression and reduced systemic toxicity. Conclusions: This stoichiometric delivery feature makes CaMA a powerful tool for the development of combination chemotherapy and personalized medications for cancer treatment., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Drug delivery systems (DDS) are extensively studied to improve the solubility, stability, pharmacokinetic, and biodistribution of chemotherapeutics. However, the drug delivery efficiency of traditional DDS is often limited by the complicated biological barriers in vivo. Herein, a multistage adaptive nanoparticle (MAN) that simultaneously overcomes multiple biological barriers to achieve tumor-targeted drug delivery with high efficiency is presented. MAN has a core-shell structure, in which both the core and the shell are made of responsive polymers. This structure allows MAN to present different surface properties to adapt to its surrounding biological microenvironment, thereby achieving enhanced stability in blood circulation, improved tumor accumulation and cellular internalization in tumor tissues, and effective release of drug in cells. With these unique characteristics, the MAN loaded with docetaxel achieves effective tumor suppression with reduced systemic toxicity. Furthermore, MAN can load almost any hydrophobic drugs, providing a general strategy for the tumor-targeted delivery of hydrophobic drugs to overcome the multiple biological barriers and improve the efficacy of chemotherapy., (© 2021 Wiley-VCH GmbH.)

With the failure of various amyloid-β-targeted drugs for Alzheimer's disease (AD) in clinical trials, tau protein has gained growing attention as an alternative therapeutic target in recent years. The aggregation of tau exerts neurotoxicity, and its spreading in the brain is associated with increasing severity of clinical symptoms for AD patients; thus tau-targeting therapies hold great potential against AD. Here, a tau-targeted multifunctional nanoinhibitor based on self-assembled polymeric micelles decorated with tau-binding peptide is devised for AD treatment. Through the multivalent binding effect with the aggregating protein, this nanoinhibitor is capable of efficiently inhibiting tau protein aggregation, recognizing tau aggregates, and blocking their seeding in neural cells, thus remarkably mitigating tau-mediated cytotoxicity. Moreover, the formed nanoinhibitor-tau complex after binding is more easily degraded than mature tau aggregates, which will be conducive to enhance the therapeutic effect. We believe that this multifunctional nanoinhibitor will promote the development of new antitau strategies for AD treatment.

Antibodies have shown potential to deplete immunosuppressive factors in tumor tissues. However, intrinsic drawbacks, including time-consuming processes in preparation, high cost, and short half-life time, greatly restrict their applications. In this work, we report an antibody-like polymeric nanoparticle (APN) that is capable of specifically capturing and removing galectin-1 in tumor tissues, thereby enhancing the antitumor T-cell responses. The APN is composed of an albumin-polymer hybrid nanoparticle (core) and an acid-responsive PEG shell. The core of the APN contains multiple recognition units and Tuftsin peptides to capture target factors and activate macrophage-mediated phagocytosis, respectively. By employing galactose as recognition units, the APN facilitated the phagocytosis of galectin-1 in tumor tissues, thereby improving the antitumor responses of tumor-infiltrating T cells. Since the recognition units in the APN can be further replaced to capture and remove other peptides/proteins, the APN provides a feasible approach for the development of synthetic nanoformulations to regulate biological systems and treat diseases.

Combination chemotherapy refers to the use of multiple drugs to treat cancer. In this therapy, the optimal ratio of the drugs is essential to achieve drug synergism and the desired therapeutic effects. However, most delivery strategies are unable to precisely control the ratio of the drugs during the drug loading and delivery processes, resulting in inefficient synergy and unpredictable efficacy. Herein, a macrocyclic-amphiphile-based self-assembled nanoparticle (MASN) that achieves precise loading and ratiometric delivery of therapeutic combinations is presented. By integrating multiple macrocyclic cavities within a single nanoparticle, the MASN can load multiple drug molecules via the host-guest interaction, and the ratio of the drugs loaded can be predicted with their initial concentrations and characteristic binding affinity. Moreover, MASNs are readily degraded under a hypoxic microenvironment, allowing spontaneous release of the drugs upon reaching tumor tissues. With precise drug loading and controlled release mechanisms, MASNs achieve ratiometric delivery of multiple commercial drugs to tumors, thereby achieving optimal anti-tumor effects. Since the optimal drug ratio of a therapeutic combination can be quickly determined in vitro, MASNs can translate this optimal ratio to the therapeutic benefits in vivo, providing a potential platform for the rapid development of effective combination cancer therapies involving multiple drugs., (© 2021 Wiley-VCH GmbH.)

Combination therapy based on molecular drugs and therapeutic genes provides an effective strategy for malignant tumor treatment. However, effective gene and drug combinations for cancer treatment are limited by the widespread antagonism between therapeutic genes and molecular drugs. Herein, a calixarene-embedded nanoparticle (CENP) is developed to co-deliver molecular drugs and therapeutic genes without compromising their biological functions, thereby achieving interference-free gene-drug combination cancer therapy. CENP is composed of a cationic polyplex core and an acid-responsive polymer shell, allowing CENP loading and delivering therapeutic genes with improved circulation stability and enhanced tumor accumulation. Moreover, the introduction of carboxylated azocalix[4]arene, which is a hypoxia-responsive calixarene derivatives, in the polyplex core endows CENP with the capability to load molecular drugs through the host-guest complexation as well as inhibit the interference between the drugs and genes by encapsulating the drugs into its cavity. By loading doxorubicin and a plasmid DNA-based CRISPR interference system that targets miR-21, CENP exhibits the significantly enhanced anti-tumor effects in mice. Considering the wide variety of calixarene derivatives, CENP can be adapted to deliver almost any combination of drugs and genes, providing the potential as a universal platform for the development of interference-free gene-drug combination cancer therapy., (© 2021 Wiley-VCH GmbH.)

The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated protein 9 (Cas9) system holds great promise for the cancer gene therapy. However, due to complicated signal networks and various compensatory mechanisms in tumors, adjusting a single molecular pathway has limited effects on cancer treatments. Herein, a virus-like nanoparticle (VLN) was reported as a versatile nanoplatform to co-deliver CRISPR/Cas9 system and small molecule drugs for effective malignant cancer treatment. VLN has a core-shell structure, in which small molecule drugs and CRISPR/Cas9 system are loaded in the mesoporous silica nanoparticle (MSN)-based core, which is further encapsulated with a lipid shell. This structure allows VLN maintaining stable during blood circulation. As reaching tumors, VLN releases the CRISPR/Cas9 system and small molecule drugs in response to the reductive microenvironment, resulting in the synergistic regulation of multiple cancer-associated pathways. By loading a single guide RNA (sgRNA) targeting programmed death-ligand 1 and axitinib, VLN achieved to disrupt multiple immunosuppressive pathways and suppress the growth of melanoma in vivo. More importantly, VLN can co-deliver almost any combination of sgRNAs and small molecule drugs to tumors, suggesting the great potential of VLN as a general platform for the development of advanced combination therapies against malignant tumors., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) enzyme, Cas13a, holds great promise in cancer treatment due to its potential for selective destruction of tumor cells via collateral effects after target recognition. However, these collateral effects do not specifically target tumor cells and may cause safety issues when administered systemically. Herein, a dual-locking nanoparticle (DLNP) that can restrict CRISPR/Cas13a activation to tumor tissues is described. DLNP has a core-shell structure, in which the CRISPR/Cas13a system (plasmid DNA, pDNA) is encapsulated inside the core with a dual-responsive polymer layer. This polymer layer endows the DLNP with enhanced stability during blood circulation or in normal tissues and facilitates cellular internalization of the CRISPR/Cas13a system and activation of gene editing upon entry into tumor tissue. After carefully screening and optimizing the CRISPR RNA (crRNA) sequence that targets programmed death-ligand 1 (PD-L1), DLNP demonstrates the effective activation of T-cell-mediated antitumor immunity and the reshaping of immunosuppressive tumor microenvironment (TME) in B16F10-bearing mice, resulting in significantly enhanced antitumor effect and improved survival rate. Further development by replacing the specific crRNA of target genes can potentially make DLNP a universal platform for the rapid development of safe and efficient cancer immunotherapies., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Current cancer immunotherapies including chimeric antigen receptor (CAR)-based therapies and checkpoint immune inhibitors have demonstrated significant clinical success, but always suffer from immunotoxicity and autoimmune disease. Recently, nanomaterial-based immunotherapies are developed to precisely control in vivo immune activation in tumor tissues for reducing immune-related adverse events. However, little consideration has been put on the spatial modulation of interactions between immune cells and cancer cells to optimize the efficacy of cancer immunotherapies. Herein, a rational design of immunomodulating nanoparticles is demonstrated that can in situ modify the tumor cell surface with natural killer cell (NK cell)-activating signals to achieve in situ activation of tumor-infiltrating NK cells, as well as direction of their antitumor immunity toward tumor cells. Using these immunomodulating nanoparticles, the remarkable inhibition of tumor growth is observed in mice without noticeable side effects. This study provides an accurate immunomodulation strategy that achieves safe and effective antitumor immunity through in situ NK cell activation in tumors. Further development by constructing interactions with various immune cells can potentially make this nanotechnology become a general platform for the design of advanced immunotherapies for cancer treatments., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Because of their abnormal vasculature and the dense tumor extra-cellular matrix, solid tumors prevent the deep and uniform penetration of nanocarriers. Numerous studies have shown that nanocarriers with a positively charged surface exhibit enhanced tumor penetration. Therefore, a hypoxia responsive nanocarrier [responsive micelles (RMs)] was developed, which can gradually increase the positive surface charge by responding to hypoxia gradients, and eventually achieve deep penetration in tumors. The nanocarrier was composed of a poly(caprolactone) core and a mixed shell of poly(ethylene glycol) (PEG) and 4-nitrobenzyl chloroformate (NBCF)-modified polylysine (PLL). During the blood circulation, the NBCF-modified PLL was shielded by the PEG, which gave it the ability to inhibit its rapid removal by the immune system. After reaching the tumor, the hypoxia microenvironment triggered partial NBCF degradation that recovered the amine groups of PLL, leading to a remarkable change in the surface to a positively charged one that enabled the penetration of the nanocarrier into the tumor. As the nanocarrier penetrated into the interior of the tumor, the decrease in oxygen concentration led to the further degradation of the NBCF-modified PLL, resulting in the increase of the positive surface charge which further facilitated the deep penetration. The subsequent in vitro and in vivo experiments certified that RM/doxorubicin had a better penetration ability and improved inhibition efficacy on tumor tissues, which demonstrated its potential application in cancer therapy.

Novel artificial enzymes are highly desired to overcome the shortcomings of natural enzymes during industrial or biological applications. Here we designed and prepared nanogel-based artificial enzymes (NAEs) to mimic natural horseradish peroxidase (HRP) using a facile one-pot, scalable method. The poly(N-isopropylacrylamide) (PNIPAM) matrix provided a temperature-responsive and size-controllable scaffold for the NAEs, and 1-vinylimidazole (Vim) moieties stabilized the enzymatic centers (Hemin) through coordination interaction. The feeding ratios of the components to prepare NAEs were subsequently studied and optimized to ensure the NAEs possess the highest catalytic activity and stability. The optimized NAEs were quite stable and can maintain their catalytic activities over a broad range of heat or pH treatments, and a long storage period as well. The NAEs are active to catalytic oxidation of several azo compounds and their activities can easily be switched on/off by changing the surrounding temperature. Taken together, these easily made, highly stable, efficient and activity-switchable NAEs could mimic natural HRP while overcoming their shortcomings and have a potential in wastewater treatment and controllable catalysis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Conventional antimicrobials are becoming increasingly ineffective for treating bacterial infection due to the emergence of multi-drug resistant (MDR) pathogens. In addition, the biofilm-mode-of-growth of infecting bacteria impedes antimicrobial penetration in biofilms. Here, we report on poly(ethylene)glycol-poly(β-amino esters) (PEG-PAE) micelles with conjugated antimicrobials, that can uniquely penetrate biofilms, target themselves to bacterial cell surfaces once inside the low-pH environment of a biofilm and release conjugated antimicrobials through degradation of their ester-linkage with PAE by bacterial lipases. In vitro, PEG-PAE micelles with conjugated Triclosan (PEG-PAE-Triclosan) yielded no inadvertent leakage of their antimicrobial cargo and better killing of MDR Staphylococcus aureus, Escherichia coli and oral streptococcal biofilms than Triclosan in solution. In mice, PEG-PAE-Triclosan micelles with conjugated Triclosan yielded better eradication efficacy towards a MDR S. aureus-infection compared with Triclosan in solution and Triclosan-loaded micelles at equal Triclosan-equivalent concentrations. Ex vivo exposure of multi-species oral biofilms collected from orthodontic patients to PEG-PAE-Triclosan micelles, demonstrated effective bacterial killing at 30-40 fold lower Triclosan-equivalent concentrations than achieved by Triclosan in solution. Importantly, Streptococcus mutans, the main causative organism of dental caries, was preferentially killed by PEG-PAE-Triclosan micelles. Thus PEG-PAE-Triclosan micelles present a promising addendum to the decreasing armamentarium available to combat infection in diverse sites of the body. STATEMENT OF SIGNIFICANCE: pH-adaptive polymeric micelles with conjugated antimicrobials can efficiently eradicate infectious biofilms from diverse body sites in mice and men. An antimicrobial was conjugated through an ester-linkage to a poly(ethylene glycol) (PEG)/poly(β-amino ester) block copolymer to create micellar nanocarriers. Stable micelle structures were formed by the hydrophobic poly(β-amino ester) inner core and a hydrophilic PEG outer shell. Thus formed PEG-PAE-Triclosan micelles do not lose their antimicrobial cargo underway to an infection site through the blood circulation, but penetrate and accumulate in biofilms to release antimicrobials once inside a biofilm through degradation of its ester-linkage by bacterial lipases, to kill biofilm-embedded bacteria at lower antimicrobial concentrations than when applied in solution. PEG-PAE-Triclosan micelles effectively eradicate biofilms of multi-drug-resistant pathogens and oral bacteria, most notably highly cariogenic Streptococcus mutans, in mice and men respectively, and possess excellent clinical translation possibilities., (Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Recently, zwitterionic materials have been developed as alternatives to PEG for prolonging the circulation time of nanoparticles without triggering immune responses. However, zwitterionic coatings also hindered the interactions between nanoparticles and tumor cells, leading to less efficient uptake of nanoparticles by cancer cells. Such effect significantly limited the applications of zwitterionic materials for the purposes of drug delivery and the development to novel therapeutic agents. To overcome these issues, surface-adaptive mixed-shell micelles (MSMs) with poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC)/poly(β-amino ester) (PAE) heterogeneous surfaces were constructed. Owing to the synergistic effect of zwitterionic coatings and micro-phase-separated surfaces, PMPC mixed-shell micelles exhibited the improved blood circulation time compared to single-PEG-shell micelles (PEGSMs) and single-PMPC-shell micelles (PMPCSMs). Moreover, such MSMs can convert their surface to positively charged ones in response to the acidic tumor microenvironment, leading to a significant enhancement in cellular uptake of MSMs by tumor cells. This strategy demonstrated a general approach to enhance the cellular uptake of zwitterionic nanoparticles without compromising their long circulating capability, providing a practical method for improving the tumor-targeting efficiency of particulate drug delivery systems., Statement of Significance: Herein we demonstrate a general strategy to integrate non-fouling zwitterionic surface on the nanoparticles without compromising their capability of tumor accumulation, by constructing a surface-adaptive mixed-shell micelles (MSMs) with poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC)/poly(β-amino ester) (PAE) heterogeneous surfaces. At the blood pH (7.4), PAE chains collapsed to the inner of the shell due to the deprotonation, and the forming micro-phase separation structure was synergistic with zwitterionic surface to prolong the circulation time of MSMs in the blood. While at the tumor sites, PAE was protonated, and the positively charged surface of MSMs enhanced cellular uptake. This self-assembly-based strategy is compatible to other zwitterionic materials, endowing a great flexibility for the construction of responsive drug delivery systems particularly to the novel chemotherapeutic agents., (Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The folding process of a protein is inherently error-prone, owing to the large number of possible conformations that a protein chain can adopt. Partially folded or misfolded proteins typically expose hydrophobic surfaces and tend to form dysfunctional protein aggregates. Therefore, materials that can stabilize unfolded proteins and then efficiently assist them refolding to its bioactive form are of significant interest. Inspired by natural chaperonins, we have synthesized a series of polymeric nanochaperones that can facilitate the refolding of denatured proteins with a high recovery efficiency (up to 97%). Such nanochaperones possess phase-separated structure with hydrophobic microdomains on the surface. This structure allows nanochaperones to stabilize denatured proteins by binding them to the hydrophobic microdomains. We have also investigated the mechanism by which nanochaperones assist the protein refolding and established the design principles of nanochaperones in order to achieve effective recovery of a certain protein from their denatured forms. With a carefully designed composition of the microdomains according to the surface properties of the client proteins, the binding affinity between the hydrophobic microdomain and the denatured protein molecules can be tuned precisely, which enables the self-sorting of the polypeptides and the refolding of the proteins into their bioactive states. This work provides a feasible and effective strategy to recover inclusion bodies to their bioactive forms, which has potential to reduce the cost of the manufacture of recombinant proteins significantly.

Biofilms cause persistent bacterial infections and are extremely recalcitrant to antimicrobials, due in part to reduced penetration of antimicrobials into biofilms that allows bacteria residing in the depth of a biofilm to survive antimicrobial treatment. Here, we describe the preparation of surface-adaptive, Triclosan-loaded micellar nanocarriers showing (1) enhanced biofilm penetration and accumulation, (2) electrostatic targeting at acidic pH toward negatively charged bacterial cell surfaces in a biofilm, and (3) antimicrobial release due to degradation of the micelle core by bacterial lipases. First, it was established that mixed-shell-polymeric-micelles (MSPM) consisting of a hydrophilic poly(ethylene glycol) (PEG)-shell and pH-responsive poly(β-amino ester) become positively charged at pH 5.0, while being negatively charged at physiological pH. This is opposite to single-shell-polymeric-micelles (SSPM) possessing only a PEG-shell and remaining negatively charged at pH 5.0. The stealth properties of the PEG-shell combined with its surface-adaptive charge allow MSPMs to penetrate and accumulate in staphylococcal biofilms, as demonstrated for fluorescent Nile red loaded micelles using confocal-laser-scanning-microscopy. SSPMs, not adapting a positive charge at pH 5.0, could not be demonstrated to penetrate and accumulate in a biofilm. Once micellar nanocarriers are bound to a staphylococcal cell surface, bacterial enzymes degrade the MSPM core to release its antimicrobial content and kill bacteria over the depth of a biofilm. This constitutes a highly effective pathway to control blood-accessible staphylococcal biofilms using antimicrobials, bypassing biofilm recalcitrance to antimicrobial penetration.

Simultaneous delivery of multiple genes and proteins (e.g., transcription factors; TFs) is an emerging issue surrounding therapeutic research due to their ability to regulate cellular circuitry. Current gene and protein delivery strategies, however, are based on slow batch synthesis, which is ineffective, poorly controlled, and incapable of simultaneous delivery of both genes and proteins with synergistic functions. Consequently, advances in this field have been limited to in vitro studies. Here, by integrating microfluidic technologies with a supramolecular synthetic strategy, we present a high-throughput approach for formulating and screening multifunctional supramolecular nanoparticles (MFSNPs) self-assembled from a collection of functional modules to achieve simultaneous delivery of one gene and TF with unprecedented efficiency both in vitro and in vivo. We envision that this new approach could open a new avenue for immunotherapy, stem cell reprogramming, and other therapeutic applications., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Polymeric nanoparticles with glucose-responsiveness are of great interest in developing a self-regulated drug delivery system. In this work, glucose-responsive polymer vesicles were fabricated based on the complexation between a glucosamine (GA)-containing block copolymer PEG45-b-P(Asp-co-AspGA) and a phenylboronic acid (PBA)-containing block copolymer PEG114-b-P(Asp-co-AspPBA) with α-CD/PEG45 inclusion complex as the sacrificial template. The obtained polymer vesicles composed of cross-linked P(Asp-co-AspGA)/P(Asp-co-AspPBA) layer as wall and PEG chains as both inner and outer coronas. The vesicular morphology was observed by transmission electron microscopy (TEM), and the glucose-responsiveness was investigated by monitoring the variations of hydrodynamic diameter (Dh) and light scattering intensity (LSI) in the polymer vesicle solution with glucose using dynamic light scattering (DLS). Vancomycin as a model drug was encapsulated in the polymer vesicles and sugar-triggered drug release was carried out. This kind of polymer vesicle may be a promising candidate for glucose-responsive drug delivery.

Exploring ideal nanocarriers for drug delivery systems has encountered unavoidable hurdles, especially the conflict between enhanced cellular uptake and prolonged blood circulation, which have determined the final efficacy of cancer therapy. Here, based on controlled self-assembly, surface structure variation in response to external environment was constructed toward overcoming the conflict. A novel micelle with mixed shell of hydrophilic poly(ethylene glycol) PEG and pH responsive hydrophobic poly(β-amino ester) (PAE) was designed through the self-assembly of diblock amphiphilic copolymers. To avoid the accelerated clearance from blood circulation caused by the surface exposed targeting group c(RGDfK), here c(RGDfK) was conjugated to the hydrophobic PAE and hidden in the shell of PEG at pH 7.4. At tumor pH, charge conversion occurred, and c(RGDfK) stretched out of the shell, leading to facilitated cellular internalization according to the HepG2 cell uptake experiments. Meanwhile, the heterogeneous surface structure endowed the micelle with prolonged blood circulation. With the self-regulated multifunctional collaborated properties of enhanced cellular uptake and prolonged blood circulation, successful inhibition of tumor growth was achieved from the demonstration in a tumor-bearing mice model. This novel nanocarrier could be a promising candidate in future clinical experiments.

In the past decades, polymer based nanoscale polymeric assemblies have attracted continuous interest due to their potential applications in many fields, such as nanomedicine. Many efforts have been dedicated to tailoring the three-dimensional architecture and the placement of functional groups at well-defined positions within the polymeric assemblies, aiming to augment their function. To achieve such goals, in one way, novel polymeric building blocks can be designed by controlled living polymerization methodology and advanced chemical modifications. In contrast, by focusing on the end function, others and we have been practicing strategies of cooperative self-assembly of multiple polymeric building blocks chosen from the vast library of conventional block polymers which are easily available. The advantages of such strategies lie in the simplicity of the preparation process and versatile choice of the constituent polymers in terms of their chemical structure and functionality as well as the fact that cooperative self-assembly based on supramolecular interactions offers elegant and energy-efficient bottom-up strategies. Combination of these principles has been exploited to optimize the architecture of polymeric assemblies with improved function, to impart new functionality into micelles and to realize polymeric nanocomplexes exhibiting functional integration, similar to some natural systems like artificial viruses, molecular chaperones, multiple enzyme systems, and so forth. In this Account, we shall first summarize several straightforward designing principles with which cooperative assembly of multiple polymeric building blocks can be implemented, aiming to construct polymeric nanoassemblies with hierarchal structure and enhanced functionalities. Next, examples will be discussed to demonstrate the possibility to create multifunctional nanoparticles by combination of the designing principles and judiciously choosing of the building blocks. We focus on multifunctional nanoparticles which can partially address challenges widely existing in nanomedicine such as long blood circulation, efficient cellular uptake, and controllable release of payloads. Finally, bioactive polymeric assemblies, which have certain functions closely mimicking those of some natural systems, will be used to conceive the concept of functional integration.

The miserable targeting performance of nanocarriers for cancer therapy arises largely from the rapid clearance from blood circulation and the major accumulation in the organs of the reticuloendothelial system (RES), leading to inefficient enhanced permeability and retention (EPR) effect after intravenous injection (i.v.). Herein, we reported an efficient method to prolong the blood circulation of nanoparticles and decrease their deposition in liver and spleen. In this work, we fabricated a series of mixed shell micelles (MSMs) with approximately the same size, charge and core composition but with varied hydrophilic/hydrophobic ratios in the shell through spontaneously self-assembly of block copolymers poly(ethylene glycol)-block-poly(l-lysine) (PEG-b-PLys) and poly(N-isopropylacrylamide)-block-poly(aspartic acid) (PNIPAM-b-PAsp) in aqueous medium. The effect of the surface heterogeneity on the in vivo biodistribution was systematically investigated through in vivo tracking of the (125)I-labeled MSMs determined by Gamma counter. Compared with single PEGylated micelles, some MSMs were proved to be significantly efficient with more than 3 times lower accumulation in liver and spleen and about 6 times higher concentration in blood at 1 h after i.v.. The results provide us a novel strategy for future development of long-circulating nanocarriers for efficient cancer therapy.

A multifunctional drug delivery system based on MCM-41-type mesoporous silica nanoparticles is described that behaves as if nanogates were covalently attached to the outlets of the mesopores through a highly acid-sensitive benzoic-imine linker. Tumor-specific uptake and intracellular delivery results from the pH-dependent progressive hydrolysis of the benzoic-imine linkage that starts at tumor extracellular pH = 6.8 and increases with decreasing pH. The cleavage of the benzoic-imine bond leads to the removal of the polypseudorotaxane caps and subsequent release of the payload drugs at tumor sites. At the same time, the carrier surface becomes positively charged, which further facilitates cellular uptake of the nanocarriers, thus offering a tremendous potential for targeted tumor therapy., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The silica/polymer hybrid hollow nanoparticles with channels and gatekeepers were successfully fabricated with a facile strategy by using thermoresponsive complex micelles of poly(ethylene glycol)-b-poly(N-isopropylacrylamide) (PEG-b-PNIPAM) and poly(N-isopropylacrylamide)-b-poly(4-vinylpyridine) (PNIPAM-b-P4VP) as the template. In aqueous solution, the complex micelles (PEG-b-PNIPAM/PNIPAM-b-P4VP) formed with the PNIPAM block as the core and the PEG/P4VP blocks as the mixed shell at 45 °C and pH 4.0. After shell cross-linking by 1,2-bis(2-iodoethoxyl)ethane (BIEE), tetraethylorthosilicate (TEOS) selectively well-deposited on the P4VP block and processed the sol-gel reaction. When the temperature was decreased to 4 °C, the PNIPAM block became swollen and further soluble, and the PEG-b-PNIPAM block copolymer escaped from the hybrid nanoparticles as a result of swelled PNIPAM and weak interaction between PEG and silica at pH 4.0. Therefore, the hybrid hollow silica nanoparticles with inner thermoresponsive PNIPAM as gatekeepers and channels in the silica shell were successfully obtained, which could be used for switchable controlled drug release. In the system, the complex micelles, as a template, could avoid the formation of larger aggregates during the preparation of the hybrid hollow silica nanoparticles. The thermoresponsive core (PNIPAM) could conveniently control the hollow space through the stimuli-responsive phase transition instead of calcination or chemical etching. In the meantime, the channel in the hybrid silica shell could be achieved because of the escape of PEG chains from the hybrid nanoparticles.

Thermosensitive nanoparticles with a core-shell structure were prepared by self-assembly of PCL-b-PEO-b-PNIPAAm triblock copolymers, which were synthesized by anionic ring-opening polymerization and reversible addition fragmentation chain transfer (RAFT) polymerization. At temperatures above the lower critical solution temperature (LCST), the collapse of PNIPAAm chains in the outer shell and in the core of nanoparticle caused a decrease in size, while the constantly hydrophilic PEO chains in the shell endowed nanoparticles with excellent stability in water. The release of doxorubicin from these nanoparticles showed that both the length of PNIPAAm chains and temperature have great influence on drug release, which indicates the great potential of thermosensitive nanoparticles as drug carriers.

Intra‐tumor bacteria promote tumor growth and inactivate cancer‐chemotherapeutics, causing poor treatment prognoses. Combined administration of cancer‐chemotherapeutics and antibiotics may disturb the oral and intestinal microflora in critically‐ill patients. To establish intra‐tumor co‐delivery of cancer‐chemotherapeutics and antibiotics, gemcitabine and ciprofloxacin are loaded in so‐called "self‐targeting", highly blood‐compatible, synthetic DCPA‐H2O liposomes equipped with complexed water for pH‐responsiveness. Liposomal pH‐responsiveness can be maintained by in‐shell loading of gemcitabine and in‐core loading of ciprofloxacin. These dual‐loaded liposomes are stealthily transported in the blood circulation to accumulate in the acidic environment of an infected tumor. Upon tumor self‐targeting, liposomes are fused with tumor cells and infecting bacteria and are disassembled to simultaneously release gemcitabine and ciprofloxacin. Treatment of mice with these self‐targeting liposomes yields significantly higher responses of Escherichia coli infected tumors with respect to both infection and tumor volume than gemcitabine and ciprofloxacin co‐delivered from non‐self‐targeting liposomes or free gemcitabine with or without ciprofloxacin in solution. [ABSTRACT FROM AUTHOR]

While poly(acyclic orthoester)s (PAOEs) have many appealing features for drug delivery, their application is significantly hindered by a lack of facile synthetic methods. Reported here is a simple method for synthesizing acyclic diketene acetal monomers from diols and vinyl ether, and their polymerization with a diol to first synthesize PAOEs. The PAOEs rapidly hydrolyze at lysosomal pH. With the help of a cationic lipid, ovalbumin, a model vaccine antigen was efficiently loaded into PAOEs nanoparticles using a double emulsion method. These nanoparticles efficiently delivered ovalbumin into the cytosol of dendritic cells and demonstrated enhanced antigen presentation over poly(lactic‐co‐glycolic acid) (PLGA) nanoparticles. PAOEs are promising vehicles for intracellular delivery of biopharmaceuticals and could increase the utility of poly(orthoesters) in biomedical research. [ABSTRACT FROM AUTHOR]

Bacterial infections are mostly due to bacteria in their biofilm mode-of-growth, making them recalcitrant to antibiotic penetration. In addition, the number of bacterial strains intrinsically resistant to available antibiotics is alarmingly growing. This study reports that micellar nanocarriers with a poly(ethylene glycol) shell fully penetrate staphylococcal biofilms due to their biological invisibility. However, when the shell is complemented with poly(β-amino ester), these mixed-shell micelles become positively charged in the low pH environment of a biofilm, allowing not only their penetration but also their accumulation in biofilms without being washed out, as do single-shell micelles lacking the pH-adaptive feature. Accordingly, bacterial killing of multidrug resistant staphylococcal biofilms exposed to protoporphyrin IX-loaded mixed-shell micelles and after light-activation is superior compared with single-shell micelles. Subcutaneous infections in mice, induced with vancomycin-resistant, bioluminescent staphylococci can be eradicated by daily injection of photoactivatable protoporphyrin IX-loaded, mixed-shell micelles in the bloodstream and light-activation at the infected site. Micelles, which are not degraded by bacterial enzymes in the biofilm, are degraded in the liver and spleen and cleared from the body through the kidneys. Thus, adaptive micellar nanocarriers loaded with light-activatable antimicrobials constitute a much-needed alternative to current antibiotic therapies. [ABSTRACT FROM AUTHOR]

Simultaneous delivery of multiple genes and proteins (e.g., transcription factors; TFs) is an emerging issue surrounding therapeutic research due to their ability to regulate cellular circuitry. Current gene and protein delivery strategies, however, are based on slow batch synthesis, which is ineffective, poorly controlled, and incapable of simultaneous delivery of both genes and proteins with synergistic functions. Consequently, advances in this field have been limited to in vitro studies. Here, by integrating microfluidic technologies with a supramolecular synthetic strategy, we present a high-throughput approach for formulating and screening multifunctional supramolecular nanoparticles (MFSNPs) self-assembled from a collection of functional modules to achieve simultaneous delivery of one gene and TF with unprecedented efficiency both in vitro and in vivo. We envision that this new approach could open a new avenue for immunotherapy, stem cell reprogramming, and other therapeutic applications. [ABSTRACT FROM AUTHOR]

Photothermal nanoparticles can be used for non-antibiotic-based eradication of infectious biofilms, but this may cause collateral damage to tissue surrounding an infection site. In order to prevent collateral tissue damage, we encapsulated photothermal polydopamine-nanoparticles (PDA-NPs) in mixed shell polymeric micelles, composed of stealth polyethylene glycol (PEG) and pH-sensitive poly(β-amino ester) (PAE). To achieve encapsulation, PDA-NPs were made hydrophobic by electrostatic binding of indocyanine green (ICG). Coupling of ICG enhanced the photothermal conversion efficacy of PDA-NPs from 33% to 47%. Photothermal conversion was not affected by micellar encapsulation. No cytotoxicity or hemolytic effects of PEG-PAE encapsulated PDA-ICG-NPs were observed. PEG-PAE encapsulated PDA-ICG-NPs showed good penetration and accumulation in a Staphylococcus aureus biofilm. Penetration and accumulation were absent when nanoparticles were encapsulated in PEG-micelles without a pH-responsive moiety. PDA-ICG-NPs encapsulated in PEG-PAE-micelles found their way through the blood circulation to a sub-cutaneous infection site after tail-vein injection in mice, yielding faster eradication of infections upon near-infrared (NIR) irradiation than could be achieved after encapsulation in PEG-micelles. Moreover, staphylococcal counts in surrounding tissue were reduced facilitating faster wound healing. Thus, the combined effect of targeting and localized NIR irradiation prevented collateral tissue damage while eradicating an infectious biofilm. [ABSTRACT FROM AUTHOR]

[Display omitted] • IMNP precisely delivers bindarit and alendronate to their sites of action. • IMNP's spatial control of drug release promotes the synergistic effect of drugs. • IMNP effectively depletes tumor-associated macrophages. • IMNP improves the therapeutic effects of anti-PD-1 therapy. Targeting the tumor-associated macrophages (TAMs) with combinational drugs is a promising strategy to improve immune checkpoint blocking therapies. To optimize the synergetic effect of TAM-depletion, it is required for the delivery system to deliver multiple therapeutic drugs to their corresponding action-sites. Herein, we design an immune modulating nanoparticle (IMNP) that can achieve a spatial control of the release sites of the drugs to synergistically deplete TAMs. IMNP has a core–shell structure in which the shell disassembles in acidic tumor microenvironment, resulting in the release of bindarit into the intercellular space to inhibit the recruitment of monocytes and exposing the core nCS(ALN)-Man to trigger the apoptosis of TAMs. With this unique feature, systemic administration of IMNP to tumor-bearing mice effectively eliminated TAMs and altered the immunosuppressing tumor environment, which significantly improved the anti-tumor efficacy of anti-PD-1. Considering the antitumor efficacy of chemotherapy, irradiation and vascular-targeted therapies is also counteracted by TAMs, IMNP could be further developed in combination with these therapies for cancer treatment, implying the potential as a general application to improve the efficacy of cancer therapies. [ABSTRACT FROM AUTHOR]

Polymeric nanoparticles with glucose-responsiveness underphysiologicalconditions are of great interests in developing drug delivery systemfor the treatment of diabetes. Herein, glucose-responsive complexmicelles were prepared by self-assembly of a phenylboronic acid-containedblock copolymer PEG-b-P(AA-co-APBA)and a glycopolymer P(AA-co-AGA) based on the covalentcomplexation between phenylboronic acid and glycosyl. The formationof the complex micelles with a P(AA-co-APBA)/P(AA-co-AGA) core and a PEG shell was confirmed by HNMR analysis.The glucose-responsiveness of the complex micelles was investigatedby monitoring the light scattering intensity and the fluorescence(ARS) of the micelle solutions. The complex micelles displayed anenhanced glucose-responsiveness compared to the simple PEG-b-P(AA-co-APBA) micelles and the sensitivityof the complex micelles to glucose increased with the decrease ofthe amount of P(AA-co-AGA) in the compositions. Thecytotoxicity of the polymers and the complex micelles was also evaluatedby MTT assay. This kind of complex micelles may be an excellent candidatefor insulin delivery and may find application in the treatment ofdiabetes. [ABSTRACT FROM AUTHOR]

Abstract: Micelle-supported gold composites with a polystyrene core and a poly(4-vinyl pyridine)/Au shell are synthesized using NaBH4 to reduce a mixture of micelle and HAuCl4 in acidic aqueous solution (pH ∼2). The template micelle with a polystyrene core and a poly(4-vinyl pyridine) shell is formed by self-assembly of block copolymer polystyrene-block-poly(4-vinyl pyridine). The gold nanoparticles coated onto the surfaces of the composites possess an average diameter of about 15 nm. The composites are applied to catalyze the reduction of p-nitrophenol in the presence of NaBH4, and the results indicate that the kinetic constant of the reaction increases when the composite concentration and the reaction temperature increase. In addition, research results also indicate that composites with high content of gold show higher catalytic activity and higher catalytic efficiency. [Copyright &y& Elsevier]

Abstract: In this paper, a new method to prepare polymer colloid particles stabilized by triblock copolymer with CdS nanoparticles was described. Poly(ethylene glycol-block-styrene-block-2-(dimethylamino) ethyl methacrylate) (PEG-b-PS-b-PDMAEMA) triblock copolymer was synthesized by sequential ATRP method. Micelles with CdS nanoparticles in the corona were prepared by “in situ” reaction of hydrogen sulfide with cadmium ion clusters in the corona of the micelles. The size of the CdS nanoparticles is affected by molar ratio of DMAEMA to cadmium ions and polymer concentration in the solution. When introduced into o/w emulsion the micelles reassemble on the surface of styrene oil droplets. PS colloid particles stabilized by triblock copolymer with CdS nanoparticles were achieved by suspension polymerization. TEM image indicates that CdS nanoparticles locate at the surface of the PS colloid particles. [Copyright &y& Elsevier]

Abstract: The copolymer of poly(N-isopropylacrylamide)-co-poly(4-vinylpyridine) was synthesized by free radical copolymerization of 4-vinylpyridine and N-isopropylacrylamide. The copolymer synthesized with the feed monomer ratio of 4-vinylpyridine/N-isopropylacrylamide equal to 1/3 was associated to form thermoresponsive colloid in neutral water at room temperature, the average size and the cloud-point temperature of which were 40nm and 32°C, respectively. The thermoresponsive colloid was used as scaffold to load 2-nm Au nanoparticles to form the responsive catalyst of colloid-stabilizing gold nanoparticles. The catalysis in the model reduction of 4-nitrophenol with NaBH4 suggested that the catalytic reduction could be modulated due to the thermoresponsive phase-transition of the colloid-stabilizing gold nanoparticles. That was, the catalytic reduction firstly accelerated with the increase in temperature below the cloud-point temperature and then decelerated with the increase in temperature above the cloud-point temperature of the thermoresponsive colloid-stabilizing Au nanoparticles. [Copyright &y& Elsevier]

Abstract: Amphiphilic colloids of CdS and noble metal nanoparticles, which can be dispersed both in water and organic solvents such as ethanol, -dimethylformamide, chloroform, and toluene, are studied. The amphiphilic colloidal nanoparticles are synthesized by grafting the amphiphilic and thermoresponsive polymer of thiol-terminated poly(N-isopropylacrylamide) to CdS and noble metal nanoparticles. The size and morphology of the PNIPAM-grafted colloidal nanoparticles of CdS@PNIPAM can be tuned by changing the molar ratio of PNIPAM/CdS. The size of CdS@PNIPAM nanoparticles slightly decreases first from 5.5 to 4.4 nm then slightly increases from 4.4 to 6.1 nm with the decrease in the molar ratio from 1/1 to 1/10. Spherical nanoparticles of CdS@PNIPAM are synthesized at a higher molar ratio and worm-like nanoparticles are obtained at a lower molar ratio. The resultant PNIPAM-grafted colloidal nanoparticles of CdS@PNIPAM, Au@PNIPAM, Pd@PNIPAM, and Ag@PNIPAM are thermoresponsive in water and show a cloud-point temperature at about 32.5 °C. [Copyright &y& Elsevier]

Abstract: The block copolymer poly(N-isopropylacrylamide)-b-poly(4-vinyl pyridine) (PNIPAM-b-P4VP) self-assembled into core-corona micelles with the P4VP block as core and the thermoresponsive PNIPAM block as corona in water. The diameter of the micelles was about 40nm and the lower critical solution temperature (LCST) was about 32°C. Gold nanoparticles of size ranging from 2 to 4nm were loaded in the micelles to form a responsive catalyst, the activity of which could be modulated due to the thermoresponsive PNIPAM. Below LCST, the PNIPAM chains were hydrophilic and the reactants could easily diffuse through the PNIPAM corona to reach the surface of the gold nanoparticles. Within this temperature range, the catalytic activity of the micelle-supported gold nanoparticles increased with the increase in temperature. Above LCST, the PNIPAM chains collapsed to form a hydrophobic barrier on the gold nanoparticles, which decelerated diffusion of the reactants. Within this temperature range, the activity of the micelle-supported gold nanoparticles decreased with the increase in temperature until to a minimum constant at about 38°C. [Copyright &y& Elsevier]