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Quantum dots (QDs) with unique quantum confinement effect and electro-optical properties are attractive for biomedical applications. Toxic effects of traditional semiconductor QDs made of heavy metal ions have serious safety concerns for their undesired environmental or healthy impact. Recent reports on core-shell structure modification of QDs by using biocompatible ligands or polymers is one way to be effectively minimizing toxicity effects of traditional QDs. Furthermore, designs of heave metal-free and metal-free QDs formulations are more promising alternatives, due to the non-toxic and eco-friendly nature of the starting materials. In article, we will review the recent designs of non-toxic or less toxic QDs, including carbon-based, biomolecules-based, silicon-based, and ternary I-III-VI QDs, and their biological applications (bio-imaging, drug delivery, gene therapy and immunoassay). Keywords: Quantum dots, Non-toxic, Bio-imaging, Core-shell, Metal-free

CRISPR/Cas9 (clustered regularly interspaced short palindromic repeat/clustered regularly interspaced short palindromic repeat associated proteins 9) gene editing platform is a promising therapeutic tool for genetic disorders, due to its ability to manipulate the pathogenic gene in genomic level and to easily target specific gene by manipulating single-guide RNA. However, its successful delivery remains a challenge. Up to now, great efforts have been made to explore an effective strategy for CRISPR/Cas9 delivery. But among those delivery methods, physical methods are mainly operated on cultured cells thus limited to laboratorial use; viral vectors are hindered by fetal immunogenic and carcinogenic effects thus dubious in clinical application. Therefore, cationic polymeric vectors, with the ability to interact with CRISPR/Cas9 system to form a nanoformulation as a non-viral approach, are attracting increasing attentions, due to advantages such as well protection of cargos, less limitation in payload size, low immunogenicity or carcinogenicity, potential modifications for further functions, and ease in mass production. In this review, the recent discoveries on polymeric vectors utilized in delivery of CRISPR/Cas9 system will be summarized. With emphasis on advanced features of those polymeric vectors or their nanoformulations to meet the demands of different CRISPR/Cas9 delivery forms (plasmid, mRNA or protein), the detailed illustrations on their disease treatment applications, such as cancer, diabetes or antibiotic-resistant infections, will also be reviewed. Keywords: CRISPR/Cas9, Polymeric vectors, Gene therapy, Gene delivery, Cancer therapy

Alginates of two different chain lengths were alkyne functionalized on the hydroxyl group, leaving all carboxylic groups intact. The two polymers were grafted with poly(oligo ethylene glycol methacrylate) (POEGMA) with terminal azides by copper catalyzed azide–alkyne coupling (CuAAC) yielding well-defined comb copolymers with different POEGMA to alginate ratios. The unfunctionalized carboxylic groups and POEGMA endowed self-assembly characteristics to the copolymer in the presence of CaCl2, which was then further exploited to encapsulate paclitaxel and doxorubicin at encapsulation efficiencies of up to 50%. Release kinetics of the encapsulated drugs were recorded over 7 days showing a higher rate of release for the copolymers with a smaller alginate backbone. HepG2 cells with the overexpression of p-glycoproteins/MDR-1 were established and the drug loaded polymer nanoparticles exhibited significantly higher cytotoxicity as compared to the drug alone, while the polymers alone exhibited non-toxicity. These cells were injected subcutaneously into Balb/C nude mice to establish a solid tumor model, to which intra-tumoral administration of the drug loaded nanoparticles showed a strong anti-tumor performance, particularly for the doxorubicin loaded particles which shrank the tumors almost completely, without any significant effect on the weight of the mice. These new materials demonstrate a conceptual advance in the synthesis of viable drug delivery vectors from natural materials. The low toxicity of the materials, coupled with the encapsulation efficiency and ability to overcome multi-drug resistance, makes them strong candidates for a range of pharmaceutical applications well beyond cancer therapy.

Recently, sustained release vectors, especially cyclodextrin (CD) based supramolecular carriers, have been reported to play an important role and have spurred interesting developments as novel gene delivery systems. This review will summarize the recent designs of CD-based supramolecular structures as sustained gene release systems in terms of CD-based graft copolymers, polyrotaxanes or polypseudorotaxanes, and supramolecular hydrogels; the advantages of these CD-based supramolecular carriers in terms of biocompatibility, gene transfection ability and controllable release rate by tuning the de-threading of CDs; and the applications of these CD-based supramolecular sustained gene release systems in disease treatments by taking advantage of their increase of the therapeutic gene's treatment period, thereby improving the gene transfection efficiency and avoiding repeated administration to increase patient compliance. Last but not least, the further endeavour towards CD-based supramolecular structures as more precise sustained gene release systems will also be discussed.

Pearl powder is a well-known traditional Chinese medicine for a variety of indications from beauty care to healthcare. While used for over a thousand years, there has yet to be an in-depth understanding and review in this area. The use of pearl powder is particularly growing in the biomedical area with various benefits reported due to the active ingredients within the pearl matrix itself. In this review, we focus on the emerging biomedical applications of pearl powder, touching on applications of pearl powder in wound healing, bone repairing, treatment of skin conditions, and other health indications.

A unique platform for combined photothermal and chemotherapy using PLA stereocomplex (PLA SC) micelles-induced hybrid gold nanocarriers is designed. The PLA SC micelles, made from the self-assembly of poly(ethylene glycol)-block-poly(l-lactide) (PEG-PLLA) and poly(2-(dimethylamino) ethyl methacrylate)-block-poly(d-lactide) (PDMAEMA-PDLA), for the first time are used as a template to fabricate the hybrid PLA SC@Au core-shell nanocarriers, in which the anticancer drugs are encapsulated within the core, while the Au nanoparticles are tethered in the shell via the in situ reduction of AuCl4 - by PDMAEMA. The obtained PLA SC@Au hybrid nanocarriers exhibit low toxicity and remarkable photothermal effect. Upon near-infrared laser irradiation, the on-site photothermal therapy can further induce an accelerated drug release from the hybrid nanocarrier reservoir via hyperthermia heating of the nanocarriers, thus leading to a synergistic photothermal and chemotherapy toward a significantly improved efficacy in tumor shrinkage. The as-designed PLA SC@Au hybrid nanocarriers, with their biocompatible compositions, dual-drug delivery characteristics, and combined photothermal/chemotherapy, show high potential as a novel platform for cancer treatment.

Unimolecular micelles, as a class of single-molecular micelles, are structurally stable regardless of their concentrations or alterations of the outer environment such as pH, temperature, ion strength etc. in comparison with conventional polymeric micelles. Polyester unimolecular micelles are extensively applied in bio-medical fields because of their stability, biocompatibility, biodegradability, structural-controllabilty etc. In this review, the most recent developments in polyester unimolecular micelle designs in terms of Boltorn polymer H40 core, cyclodextrin, dendrimer or dendrimer-like polymer, or polyhedral oligomeric silsesquioxane (POSS) based polyester unimolecular micelles are presented. The significance and application in biomedical fields including drug delivery, bio-imaging and theranostics are also classified in this review. Finally, the remaining challenges and future perspectives for further development of unimolecular micelles as therapeutic materials are also discussed.

Bacterial infections remain a leading threat to global health because of the misuse of antibiotics and the rise in drug-resistant pathogens. Although several strategies such as photothermal therapy and magneto-thermal therapy can suppress bacterial infections, excessive heat often damages host cells and lengthens the healing time. Here, a localized thermal managing strategy, thermal-disrupting interface induced mitigation (TRIM), is reported, to minimize intercellular cohesion loss for accurate antibacterial therapy. The TRIM dressing film is composed of alternative microscale arrangement of heat-responsive hydrogel regions and mechanical support regions, which enables the surface microtopography to have a significant effect on disrupting bacterial colonization upon infrared irradiation. The regulation of the interfacial contact to the attached skin confines the produced heat and minimizes the risk of skin damage during thermoablation. Quantitative mechanobiology studies demonstrate the TRIM dressing film with a critical dimension for surface features plays a critical role in maintaining intercellular cohesion of the epidermis during photothermal therapy. Finally, endowing wound dressing with the TRIM effect via in vivo studies in S. aureus infected mice demonstrates a promising strategy for mitigating the side effects of photothermal therapy against a wide spectrum of bacterial infections, promoting future biointerface design for antibacterial therapy. National Research Foundation (NRF) Accepted version This work was financially supported by the NTU-Northwestern Institute for Nanomedicine and the National Research Foundation, Prime Minister’s Office, Singapore, under the NRF Investigatorship (NRF-NRFI2017-07).

Nano-bio interfaces are emerging from the convergence of engineered nanomaterials and biological entities. Despite rapid growth, clinical translation of biomedical nanomaterials is heavily compromised by the lack of comprehensive understanding of biophysicochemical interactions at nano-bio interfaces. In the past decade, a few investigations have adopted a combinatorial approach toward decoding nano-bio interfaces. Combinatorial nano-bio interfaces comprise the design of nanocombinatorial libraries and high-throughput bioevaluation. In this Perspective, we address challenges in combinatorial nano-bio interfaces and call for multiparametric nanocombinatorics (composition, morphology, mechanics, surface chemistry), multiscale bioevaluation (biomolecules, organelles, cells, tissues/organs), and the recruitment of computational modeling and artificial intelligence. Leveraging combinatorial nano-bio interfaces will shed light on precision nanomedicine and its potential applications. NRF (Natl Research Foundation, S’pore) Accepted version

Fourteen new lanthanide coordination complexes based on tetracarboxyl tecton ligands, namely, [Ln(Hbtec)(H2O)2] (Ln = La (1) Ce (2) Pr (3) Nd (4) Sm (5) Gd (6) Dy (7) Ho (8) Er (9) Yb (10) Y (11)), [Yb(Hbtec)(H2O)2] (12), [Na2La2(btec)2(H2O)4]·H2O (13), and [NaPr(btec)(H2O)2] (14) (H4btec = 1,2,3,5-benzenetetracarboxylic acid) have been prepared and characterized by elemental analysis, IR spectra and X-ray diffraction. Complexes 1–11 are iso-structural, crystallizing in monoclinic P21/c space group, the lanthanide atoms are nine coordinated, and the Hbtec3− ligands bridge the Ln(III) metal oxide chain into a two-dimensional double layer structure with SP 2-periodic topology. As for complex 12, it is an isomer of complex 10. The Yb(III) atom is eight coordinated and leading a two-dimensional sheet with kgd topology in 12. The tetracarboxyl ligands are fully deprotonated into btec4− in complexes 13 and 14 with sodium atoms as counter cations. Different from the previous twelve complexes, the two complexes are flu topology three-dimensional framework with the lanthanide atoms ten coordinated. Representative thermal stabilities and photoluminescent properties were also studied.

In this report, a new star-like copolymer β-CD-g-(PNIPAAm-b-POEGA)x, consisting of a β-CD core, grafted with temperature-responsive poly(N-isopropylacrylamide) (PNIPAAm) and biocompatible poly(oligo(ethylene glycol) acrylate) (POEGA) in a block copolymer of the arms, was used to deliver chemotherapeutics to drug resistant cancer cells and tumors. The first step of the self-assembly process involves the encapsulation of chemotherapeutics through host–guest inclusion complexation between the β-cyclodextrin cavity and the anticancer drug. Next, the chain interaction of the PNIPAAm segment at elevated temperature drives the drug-loaded β-CD-g-(PNIPAAm-b-POEGA)x/PTX inclusion complex to hierarchically self-assemble into nanosized supramolecular assemblies at 37 °C, whereas the presence of poly(ethylene glycol) (PEG) chains in the distal end of the star-like copolymer arms impart enhanced stability to the self-assembled structure. More interestingly, this supramolecular host–guest nanocomplex promoted the enhan...

Two dinuclear Fe(III) metal–organic complexes with tetracarboxylate and chelating N-donor ligands, [Fe(Hbtec)(phen)(H2O)]2·2H2O (1) and [Fe(Hbtec)(bpy)(H2O)]2·2H2O (2) (H4btec = 1,2,3,5-benzenetetracarboxylic acid, phen = 1,10-phenanthroline, bpy = 2,2′-bipyridine) have been prepared and characterized by elemental analysis, IR spectroscopic, and X-ray diffraction methods. Both complexes crystallize in the monoclinic space group P21/c with two Fe(III) ions bridged by two Hbtec3− ligands into a dinuclear unit. Hydrogen bonding connects the dinuclear units into a 3-D framework. The dinuclear units are 10-connected nodes that produce a 3-D framework with topology Schläfli symbol as (312·428·55). Thermal stabilities and luminescent properties of the two complexes have also been investigated.

Even though fungal keratitis is a severe corneal disease that can lead to permanent vision loss, its therapeutic management is still problematic. This limitation is in part attributable to the fact that tear film renewal curtails exposure time of drug containing eye drops to the ocular surface. Accordingly, anti-microbial therapy needs to be performed repeatedly. Efforts to resolve this hindrance include developing formulations that prolong drug retention on the ocular surface which can in turn improve therapeutic efficacy as well as reduce administration frequency. To extend drug residence time on the ocular surface, we designed a novel organic-inorganic hybrid consisting of a PEG-PPG copolymer modified with polyhedral oligomeric silsesquioxane (POSS) groups. Its tailored POSS-micelles possess both good biocompatibility and bio-adhesiveness, which improve ocular delivery of poorly soluble drugs. We describe here use of mouse fungal keratitis model to determine the effects of this formulation encapsulating amphotericin B (AMB) on this condition. The results show that POSS-micelles significantly prolonged AMB retention time on the ocular surface, leading to improved resolution of this disease. Moreover, this treatment strategy had no toxic effects during ocular administration either in vitro or in vivo. Therefore, this POSS formulation bearing AMB has the potential to prolong drug retention time and improve its therapeutic efficacy in managing fungal keratitis.

Rational design of new wound dressing materials aims to accelerate wound healing. Traditional hydrophilic wound dressings, however, tend to cause retention of wound exudate retention, which increases the risk of bacterial infection, resulting in slower wound healing. Herein, a multifunctional amphiphilic wound dressing nanofibrous materials with Janus superhydrophilic/ superhydrophobic feature is designed to accelerate wound healing. In this design, the top superhydrophilic polycaprolactone (PCL)-Gelatin (PCL-Gelatin, WCA ~ 0°) fibers function as a pump-like suction layer that can effectively isolate wound exudate from the wound site, thereby providing drier condition which lowers the risk of wound infection. More importantly, the superhydrophobic PCL-poly(perfluorodecyl methacrylate)-block-poly(dimethylsiloxane)-block-poly(perfluorodecyl methacrylate) (PFMA-b-PDMS-b-PFMA) (PCL-PFMA, WCA ~ 140°) in contact with the wound site showed excellent anti-adhesion effect to bacterial, cells and tissues, thereby further lowering the risk of bacterial infection and preventing the secondary injuries caused by dressing changes. Sprague-Dawley (SD) rat skin lesion model demonstrated significant improvement in wound healing of the Janus amphipathic PCL-Gelatin / PCL-PFMA fiber films compared with the conventional hydrophilic- and hydrophobic-only wound dressing materials. After 14 days of treatment, the wound healing area in this group was close to 100%. To the best our acknowledge, this is a pioneer exploration of Janus amphipathic wound dressing with unidirectional drainage function and anti-adhesive ability, which may have great potential for real life usage on clinical patients.

Using 1,2,3,5-benzenetetracarboxylic acid and different pyridyl ligands, three metal-organic coordination compounds, [ $$\hbox {Co(H}_{3}\hbox {btec})(1{,}{10}\hbox {-phen})(\hbox {H}_{2}\hbox {O})_{3}$$ ][OH] $$\cdot 2\hbox {H}_{2}\hbox {O}$$ (1), [ $$\hbox {Co}_{2}$$ (btec)(2,2’-bipy) $$_{2}$$ - ( $$\hbox {H}_{2}\hbox {O}$$ )] $$\cdot \hbox {H}_{2}\hbox {O}$$ (2), {[ $$\hbox {Co}_{1.5}(\hbox {H}_{2}\hbox {btec}$$ )(4,4’-bipy)( $$\hbox {H}_{2}\hbox {O})_{2}$$ ][ $$\hbox {Co}_{0.5}$$ (4,4’-bipy)- ( $$\hbox {H}_{2}\hbox {O})_{4}][\hbox {OH}]_{2}\}\cdot 2\hbox {H}_{2}\hbox {O}$$ (3), ( $$\hbox {H}_{4}\hbox {btec} = 1,2,3,5$$ -benzenetetracarboxylic acid, 1,10-phen = 1,10-phenanthroline, 2,2’-bipy = 2, $$2^{\prime }$$ -bipyridine, 4,4’-bipy = 4, $$4^{\prime }$$ -bipyridine) were synthesized by hydrothermal method and characterized by elemental analysis, infrared spectroscopy, and single-crystal X-ray diffraction analysis. X-ray crystallographic studies reveal that 1 is a discrete 0D coordination compound, while 2 and 3 possess similar 2D network structures, which show a sql network with the point symbol of (4,4). Thermal analysis indicates that compounds 1 and 2 begin to collapse after $$350{^{\circ }}\hbox {C}$$ . Further, the UV-Vis DRS spectra and solid-state luminescent properties of 1–3 have also been studied. SYNOPSIS The reaction of benzene tetracarboxylate $$\hbox {H}_{4}\hbox {btec}$$ and pyridyl ligands (1,10-phen, 2,2’-bipy, and 4,4’-bipy) gave rise to three coordination compounds, $$[\hbox {Co(H}_{3}\hbox {btec)}(1,10\hbox {-phen)(H}_{2}\hbox {O)}_{3}][\hbox {OH}]\cdot 2\hbox {H}_{2}\hbox {O}$$ , [ $$\hbox {Co}_{2}$$ (btec)(2,2’- $$\hbox {bipy})_{2}(\hbox {H}_{2}\hbox {O})]\cdot \hbox {H}_{2}\hbox {O}$$ , $$\{[\hbox {Co}_{1.5}(\hbox {H}_{2}\hbox {btec})$$ (4,4’ $$-\hbox {bipy})(\hbox {H}_{2}\hbox {O})_{2}$$ ][ $$\hbox {Co}_{0.5}$$ (4,4’-bipy)( $$\hbox {H}_{2}\hbox {O})_{4}][\hbox {OH}]_{2}\}\cdot 2\hbox {H}_{2}\hbox {O}$$ , which exhibit discrete and 2D network structures, as shown.

Deregulation of anti-apoptosis Bcl-2 protein expression was a key feature in human cancers with therapeutic resistance. Nuclear receptor Nur77 could induce the conformation change of Bcl-2 protein and converted it into an apoptosis inducer by “enemy to friend” strategy. However, the safe and effective delivery of this gene to combat therapeutic resistant cancer remained largely unexplored. In this report, we designed an amphiphilic cationic MPEG-PCL-PEI-FA copolymer, comprising biocompatible and hydrophilic methoxy-poly(ethylene glycol) (MPEG), biodegradable and hydrophobic poly(e-caprolactone) (PCL), cationic poly(ethylene imine) (PEI) segments, and folic acid (FA) as targeting group, as a high efficient Nur77 gene carrier to folate receptor (FR) highly expressed and therapeutic resistant HeLa/Bcl-2 cancer cells. Interestingly, due to the incorporation of PCL and PEG segments, this MPEG-PCL-PEI-FA copolymer showed less toxicity but better gene transfection efficiency than non-viral gene carrier gold standard PEI (25 kDa). This might be due to the formation of micelles to stabilize polyplex for enhanced gene transfection ability. More importantly, MPEG-PCL-PEI-FA copolymer exhibited excellent growth inhibition ability on therapeutic resistant HeLa/Bcl-2 cancer cells, which was FR overexpressed HeLa cervical cancer cells with high expression of Bcl-2 protein, thanks to its FA induced targeting ability, high gene transfection efficiency, and low cytotoxicity. This work signifies the first time that cationic amphiphilic MPEG-PCL-PEI-FA copolymers could be utilized for the gene delivery to therapeutic resistant cancer cells with high expression of anti-apoptosis Bcl-2 protein and the positive results are encouraging for the further design of polymeric platforms for combating drug resistant tumors.

Two Gadolinium coordination polymers {[Gd·(TTTA)·(H2O)2]·2H2O}n (1) and [Gd·(TTTA)·DMF]n (2) have been synthesized based on Gd(NO3)3·6H2O and the flexible tripodal ligand 2,2′,2″-[1,3,5-triazine-2,4,6-triyltris(thio)]tris-acetic acid (H3TTTA) under hydrothermal conditions. In the structure of 1, the tridentate TTTA3− ligands connect the dimeric metal centers into an infinite one dimensional chain. While 2 shows a two dimensional network with tridentate TTTA3− ligands. The two complexes all quench the emission spectra after coordinated to the Gd3+ ions. The catalytic results indicate that two complexes show excellent activities for the cyanosilylation of benzaldehyde and its derivatives. Besides, 2 is better than 1 in the catalytic reactions due to more possibility of metal open sites.

In this study, a novel amphiphilic star-like CD-PCL-SS-PEG(PNIPAM) copolymer with a disulfide linkage at the junction points of the “Y”-shaped arms is designed and further fabricated into dual temperature and redox-responsive unimolecular micelles for controlled drug delivery in cancer therapy. During the synthesis, the end-alkyne functionalized hydrophobic star-like core CD-PCL-SS-alkyne was first synthesized by ring-opening polymerization (ROP) of e-CL using β-CD as an initiator, followed by a two-step end group transformation reaction. Then, CD-PCL-SS-alkyne was coupled with α,α′-azide, hydroxyl-PEG (PEG-N3(OH)) via “click” chemistry to obtain PCL-SS-(OH)PEG copolymers with reactive –OH at the junction point. Furthermore, esterification between the –OH on PCL-SS-(OH)PEG and S-1-dodecyl-S′-(α,α′-dimethyl-α′′-acetic acid)trithiocarbonate (DDAT) was carried out to afford the CD-PCL-b-(CTA)PEG copolymer, followed by reversible addition–fragmentation chain-transfer polymerization (RAFT) of N-isopropylacrylamide to obtain the desired star-like CD-PCL-SS-PEG(PNIPAM) copolymer. The targeted copolymer and its intermediates were characterized by 1H NMR and gel permeation chromatography (GPC). The unimolecular micelles formed from the CD-PCL-SS-PEG(PNIPAM) copolymer were studied by dynamic light scattering (DLS) and transmission electron microscopy (TEM) techniques. Drug release studies from CD-PCL-SS-PEG(PNIPAM) micelles exhibited sustained release profiles and the rate of release can be tuned by variation of temperature and glutathione (GSH). Cellular uptake and in vitro stimuli-mediated intracellular DOX release were investigated by flow cytometry and confocal laser scanning microscopy (CLSM) measurements, demonstrating high cellular uptake efficiency and significant intracellular drug release from doxorubicin (DOX) loaded CD-PCL-SS-PEG(PNIPAM) micelles via controlling temperature and reduction. Together with the excellent cell biocompatibility, the new star-like CD-PCL-SS-PEG(PNIPAM) copolymer reported in this paper could potentially be used as intelligent nanocarriers for controlled drug delivery.

Star fruit (Averrhoa carambola) juice rich in vitamin C and polyphenolic antioxidants was used to synthesize branched gold nanoflowers. These biocompatible and stable gold nanoflowers show strong near-infrared absorption. They are successfully demonstrated to be highly efficient for both in vitro and in vivo photothermal therapy by using an 808 nm laser.

Transcatheter arterial chemoembolization (TACE), aiming to block the hepatic artery for inhibiting tumor blood supply, became a popular therapy for hepatocellular carcinoma (HCC) patients. Traditional TACE formulation of anticancer drug emulsion in ethiodized oil (i.e., Lipiodol®) and gelatin sponge (i.e., Gelfoam®) had drawbacks on patient tolerance and resulted in undesired systemic toxicity, which were both significantly improved by polymeric beads, microparticles, or hydrogels by taking advantage of the elegant design of biocompatible or biodegradable polymers, especially amphiphilic polymers or polymers with both hydrophilic and hydrophobic chains, which could self-assemble into proposed microspheres or hydrogels. In this review, we aimed to summarize recent advances on polymeric embolization beads or hydrogels as TACE agents, with emphasis on their material basis of polymer architectures, which are important but have not yet been comprehensively summarized.

Rational design of controllable drug release systems is important for tumor treatments due to the nonspecific toxicity of many chemotherapeutics. Herein, laser or light responsive pharmaceutical delivery nanoparticles are designed, by taking the advantages of redox responsive selenium (Se) substituted polymer as shell and photosensitive porphyrin zirconium metal-organic frameworks (MOF) as core. In detail, redox cleavable di-(1-hydroxylundecyl) selenide (DH-Se), biocompatible poly(ethylene glycol) (PEG), and poly(propylene glycol) (PPG) are randomly polymerized to form poly(DH-Se/PEG/PPG urethane), which is used to coat the reactive oxygen species' (ROS) producible porous porphyrin zirconium metal organization formulation (PCN-224 MOF) to form the final poly(DH-Se/PEG/PPG urethane)@MOF shell-core nanoparticle with spherical shape by emulsion approach. Interestingly, poly(DH-Se/PEG/PPG urethane)@MOF nanoparticles with loading of chemotherapeutic doxorubicin (DOX) experience a fast and controllable release, which can realize the combination of chemotherapy and photodynamic therapy upon irradiation with laser light, due to the light-triggered ROS production by MOF which further causes the cleavage of poly(DH-Se/PEG/PPG urethane) polymer chain and the release of encapsulated DOX. To the best of the authors' knowledge, this is the first design of utilizing MOF and selenium substituted polymer as controllable drug release carriers, which might be beneficial for precise chemotherapy and photodynamic therapy combination.

Local mechanical cues can affect crucial fate decisions of living cells. Transepithelial stress has been discussed in the context of epithelial monolayers, but the lack of appropriate experimental systems leads current studies to approximate it simply as an in‐plane stress. To evaluate possible contribution of force vectors acting in other directions, double epithelium in a 3D‐printed “GeminiChip” containing a sessile and a pendant channel is reconstituted. Intriguingly, the sessile epithelia is prone to apoptotic cell extrusion upon crowding, whereas the pendant counterpart favors live cell delamination. Transcriptome analyses show upregulation of RhoA, BMP2, and hypoxia‐signaling genes in the pendant epithelium, consistent with the onset of an epithelial–mesenchymal transition program. HepG2 microtumor spheroids also display differential spreading patterns in the sessile and pendant configuration. Using this multilayered GeminiChip, these results uncover a progressive yet critical role of perpendicular force vectors in collective cell behaviors and point at fundamental importance of these forces in the biology of cancer. NRF (Natl Research Foundation, S’pore) Accepted version

Three new lead(II) metal-organic coordination complexes constructed with tetracarboxyl tecton, namely, [Pb2(btec)] (1), [Pb3(µ4-O)(btec)(H2O)2]·H2O (2), and [Pb(btec)0.5(phen)] (3) (H4btec = 1,2,3,5-benzenetetracarboxylic acid, phen = 1,10-phenanthroline), have been prepared and characterized. A three-dimensional framework containing Pb(II) metal oxide sheet is being obtained in complex 1. Interestingly, a rather rare hexanuclear [Pb6(µ4-O2−)2]8+ octahedral core appeared in 2. The hexanuclear units are further connected by the btec4− ligands into a three-dimensional framework. When phen ligand was used as auxiliary coligand, a three-dimensional framework containing Pb2O2 dimer as building unit was observed in complex 3. Thermal stabilities and photoluminescent properties of complexes 1–3 have also been investigated. Three new lead(III) metal–organic coordination complexes were prepared under hydrothermal methods by the reaction of 1,2,3,5-benzenetrtracarboxylic acid and corresponding Pb(II) salts with or without auxiliary N-donor chelating ligands. Four kinds of coordination number with six different types of coordination sphere demonstrated in the Pb(II) atoms. A three-dimensional framework containing Pb-O metal oxide sheet bridged by btec4− into (4,5,9)-connected (418·618)(45·6)(46·64) topology demonstrated in complex 1. In complex 2, a rather rare hexanuclear [Pb6(µ4-O2−)2]8+ acts as building unit, which bridged by btec4− into a three-dimensional framework with flu topology. While in complex 3, a three-dimensional framework composed with Pb2O2 dimers bridged by btec4− ligands into pts topology demonstrated. The results show both coordination modes of H4btec ligands and center Pb(II) atoms do great influence on the final products and supramolecular structures.

Four new zinc(II) and cadmium(II) metal–organic coordination complexes with tetracarboxyl tecton and N-donor chelating ligands, namely, [Zn2(H2btec)2(bpy)2(H2O)2]·4H2O (1), [Zn4(btec)2(bpy)4(H2O)6]·2H2O (2), [Zn2(btec)(phen)H2O]·2H2O (3), and [Cd3(H2btec)2(phen)4(H2O)2]·2NO3 (4) (H4btec = 1,2,3,5-benzenetetracarboxylic acid, bpy = 2,2′-bipyridyl, phen = 1,10-phenanthroline), have been prepared and characterized by elemental analysis, IR spectra and X-ray diffraction. Bi-nuclear and tetra-nuclear complexes are being observed in complexes 1 and 2, respectively, which attribute to the different deprotonation of H4btec ligands, further leading different coordination modes. Interestingly, both octahedral and triangular prism coordination environments display in complex 2. However, when phen substituted the bpy as auxiliary coligand, a two-dimensional sheet was observed in complex 3. Interestingly, when the transition metal ion was changed into Cd(II) in complex 4, the H4btec ligands are deprotonated into H2btec2− ligand with the help of nitrate group as counter ion, the Cd(II) atoms bridged the H2btec2− ligands into a one-dimensional chain. Thermal stabilities and photoluminescent properties of complexes 1–4 have also been investigated.

Four novel metal–organic coordination polymers constructed from 1,2,3,5-benzenetetracarboxylic acid and bridging dipyridyl ligands, namely, [Zn(H2btec)(bpy)0.5] (1), [Zn(H2btec)(bpyE)0.5] (2), [Zn2(btec)(bpye)H2O]·2H2O (3), and [Zn(Hbtec)(Hbpyp)]·H2O (4) (H4btec = 1,2,3,5-benzenetetracarboxylic acid, bpy = 4,4′-bipyridine, bpyE = 1,2-bis(4-pyridyl)ethylene, bpye = 1,2-bis(4-pyridyl)ethane, bpyp = 1,3-bis(4-pyridyl)propane) have been synthesized with hydrothermal methods and characterized by elemental analysis, IR, TGA, and single crystal X-ray diffraction. All the zinc(II) atoms are four coordinated in the four complexes, the different nitrogen coligands were found to remarkably affect the framework topologies. The zinc(II) atoms are bridged by H2btec2− with adjacent carboxylate groups into a one-dimensional double chain in complexes 1 and 2, the chains are further connected into a two dimensional sheet by the rigid dipyridyl ligands in the two complexes. However, the H4btec ligands are deprotoned into btec4− ligand and act as five-dentated ligands, which connect the zinc(II) atoms into a two-dimensional double layer with the help of flexible bpye ligands in complex 3. Interestingly, the H4btec ligands are deprotoned into Hbtec3− ligand rather than H2btec2− and btec4− in complex 4, and the three adjacent carboxylate groups connected the zinc(II) atoms into another kind of one dimensional double chain. Different from complexes 1, 2, and 3, the bpyp is protonated and acts as a terminal ligand rather than bridging one, the protonated N–H groups form hydrogen bonding interactions with the adjacent chain and thus bridging the chains into a two-dimensional sheet. Besides the coordination mode of the H4btec ligands, the final structures are also influenced greatly by the hydrogen bonding interactions of the H4btec ligands, one-dimensional channel constructed via hydrogen bonding interactions of H4btec ligands in complexes 1, 2, and 4 with dipyridyl ligands as guest molecules. Thermal stabilities and photoluminescent properties of complexes 1–4 were also examined.

A thermogelling poly(ester urethane) comprising poly(ethylene glycol) (PEG), poly(propylene glycol) (PPG) and poly(lactic acid) (PLA) blocks was synthesized. Drug release studies of the thermogel were carried out using paclitaxel (PTX). The release rate of the drug can be achieved by changing the concentration of the gel, greatly prolonging the release and elimination times to afford long-term effects. The thermogels showed very low toxicity on HEK293 cells. A nude mice model of hepatocellular carcinoma was developed and intratumoural injection of drug-loaded thermogel showed that PTX-loaded thermogel effectively inhibited the growth of tumours.

A dual-emission pH-sensitive fluorescent probe was developed, which displays green fluorescence in alkaline after deprotonation, while orange emission in acid at aggregated state. This novel probe allows the specific light-on in acidic lysosomes of cancer cells and tumors in nude mice, which indicates its potential application in cancer diagnosis.

Docetaxel (DTX) is a new semisynthetic chemical in the taxoid family and serves a wide spectrum of chemotherapeutics. Current commercial formulation of DTX is based on the addition of the nonionic surfactants (i.e., ethanol and Tween 80), which are reported to cause severe hemolysis, hypersensitivity reactions, or neurotoxic toxicity and greatly hinders patient tolerance or compliance. In this report, a novel low-toxic, biodegradable, and amphiphilic poly[(R)-3-hydroxybutyrate-(R)-3-hydroxyhexanoate] (PHBHx)-based polyurethane (a copolymer made of hydrophobic PHBHx with biocompatible D-3-hydroxybutyric acid as degradation product, thermosensitive polypropylene glycol (PPG), and hydrophilic polyethylene glycol (PEG) segments) with nanosized micelle formation ability to encapsulate DTX, as a surfactant free formulation, is reported. Interestingly, this DTX-loaded poly(PHBHx/PEG/PPG urethane) micelle formulation with >90% drug loading efficiency shows significantly improved DTX solubility in aqueous medium, reduced hemolysis for better blood compatibility, and increased drug uptake in A375 melanoma cells, which provides the possibility of systematic delivery of DTX. As a proof-of-concept, an A375 melanoma xenograft mouse model is established to verify the therapeutic effect of this DTX-loaded poly(PHBHx/PEG/PPG urethane) micelle formulation, indicating the promising application of PHBHx-based polymeric nanosized micelle as a surfactant free formulation of chemotherapeutics which might greatly be beneficial for controllable delivery of pharmaceutics and cancer therapy.

An amphiphilic star-shaped copolymer β-CD-g-PCL-SS-PEG-FA, consisting of a β-cyclodextrin (β-CD) core as well as grafted with bioreducible disulfide linkage in PCL-SS-PEG multiarms and targeting folic acid (FA) as end moiety, is designed with unimolecular micelles formation ability for targeted transport of chemotherapeutics to drug resistant tumor cells. Firstly, β-CD was utilized as core to growth PCL arms by ring-opening polymerization (ROP) of ε-CL, before disulfide terminal group transformation to render β-CD-g-PCL-SS-COOH. Secondly, α-hydroxy-ω-amine protected PEG (HO-PEG-NHBoc) was connected to β-CD-g-PCL-SS-COOH to obtain amphiphilic β-CD-g-PCL-SS-PEG, where PCL and PEG were connected via bioreducible disulfide bond. After deprotection of -Boc group, FA was introduced onto the distal end of block arms to obtain the desired β-CD-g-PCL-SS-PEG-FA copolymer. Because of highly branched core-shell amphiphilic structures, β-CD-g-PCL-SS-PEG-FA could act as unimolecular micelles. Interestingly, this unimolecular micelle could release the encapsulated drug in a glutathione (GSH) dependent manner due to disulfide linkage. More importantly, this unimolecular micelle could load doxorubicin (DOX) to promote its cellular uptake in multidrug resistance (MDR) protein overexpression tumor cells, by taking the advantage of FA targeting group and intracellular high GSH level in cancer cells. Together with satisfactory biocompatibility, this novel star-like β-CD-g-PCL-SS-PEG-FA unimolecular micelle could potentially be utilized as targeting nanocarriers in drug resistant cancer therapy.

The emergence of drug-resistant microbes has become a threat to global health, and microbial infections severely limit the use of healthcare materials. To achieve efficient antimicrobial therapy, supramolecular hydrogels demonstrate unprecedented advantages in medical applications due to the tunable and reversible nature of their supramolecular interactions and the capability of hydrogels to incorporate various therapeutic agents. Herein, antimicrobial hydrogels are categorized according to their inherent antimicrobial properties or based on their roles in encapsulating antimicrobial materials. Moreover, strategies to further enhance the antimicrobial efficacy of hydrogels are highlighted, such as the incorporation of antifouling agents or the enabling of response towards physiological cues. We envision that supramolecular hydrogels, in combination with modern medical technology and devices, will contribute to the development of efficient and safe systems for antimicrobial therapy. NRF (Natl Research Foundation, S’pore) Accepted version

Stem cell culturing and differentiation is a very important research direction for tissue engineering. Thermogels are well suited for encapsulating cells because of their non-biotoxic nature and mild sol-gel transition as temperature increases. In particular, thermogels provide a 3D growth environment for stem cell growth, which is more similar to the extracellular matrix than flat substrates, so thermogels as a medium can overcome many of the cell abnormalities caused by 2D cell growth. In this review, we summarize the applications of thermogels in cell and stem cell culture in recent years. We also elaborate on the methods to induce stem cell differentiation by using thermogel-based 3D scaffolds. In particular, thermogels, encapsulating specific differentiation-inducing factor and having specific structures and moduli, can induce the differentiation into the desired tissue cells. Three dimensional thermogel scaffolds that control the growth and differentiation of cells will undoubtedly have a bright future in regenerative medicine.

The reciprocal mechanical interaction of engineered materials with biointerfaces have long been observed and exploited in biomedical applications. It contributes to the rise of biomechano-responsive materials and biomechano-stimulatory materials, constituting the biomechano-interactive interfaces. Here, endogenous and exogenous biomechanical stimuli available for mechanoresponsive interfaces are briefed and their mechanistic responses, including deformation and volume change, mechanomanipulation of physical and chemical bonds, dissociation of assemblies, and coupling with thermoresponsiveness are summarized. The mechanostimulatory materials, however, are capable of delivering mechanical cues, including stiffness, viscoelasticity, geometrical constraints, and mechanical loads, to modulate physiological and pathological behaviors of living tissues through the adaptive cellular mechanotransduction. The biomechano-interactive materials and interfaces are widely implemented in such fields as mechanotriggered therapeutics and diagnosis, adaptive biophysical sensors, biointegrated soft actuators, and mechanorobust tissue engineering, which have offered unprecedented opportunities for precision and personalized medicine. Pending challenges are also addressed to shed a light on future advances with respect to translational implementations. NRF (Natl Research Foundation, S’pore) MOE (Min. of Education, S’pore) Accepted version

Tactile sensors capable of perceiving biophysical signals such as force, pressure, or strain have attracted extensive interest for versatile applications in electronic skin, noninvasive healthcare, and biomimetic prostheses. Despite these great achievements, they are still incapable of detecting bio/chemical signals that provide even more meaningful and precise health information due to the lack of efficient transduction principles. Herein, a tactile chemomechanical transduction strategy that enables the tactile sensor to perceive bio/chemical signals is proposed. In this methodology, pyramidal tactile sensors are linked with biomarker‐induced gas‐producing reactions, which transduce biomarker signals to electrical signals in real time. The method is advantageous as it enhances electrical signals by more than tenfold based on a triple‐step signal amplification strategy, as compared to traditional electrical biosensors. It also constitutes a portable and general platform capable of quantifying a wide spectrum of targets including carcinoembryonic antigen, interferon‐γ, and adenosine. Such tactile chemomechanical transduction would greatly broaden the application of tactile sensors toward bio/chemical signals perception which can be used in ultrasensitive portable biosensors and chemical‐responsive chemomechanical systems. NRF (Natl Research Foundation, S’pore) MOE (Min. of Education, S’pore) Accepted version

In this study, we report the synthesis and characterisation of a thermogelling poly(carbonate urethane) system comprising poly(ethylene glycol) (PEG), poly(propylene glycol) (PPG) and poly(polytetrahydrofuran carbonate) (PTHF carbonate). The incorporation of PTHF carbonate allowed for the control of the lower critical solution temperature (LCST) and decreased critical gelation concentration (CGC) of the thermogels significantly. In addition, the as-prepared thermogels displayed low toxicity against HepG2, L02 and HEK293T cells. Drug release studies were carried out using doxorubicin (Dox). Studies conducted using nude mice models with hepatocellular carcinoma revealed that the Dox-loaded poly(PEG/PPG/PTHF carbonate urethane) thermogels showed excellent in vivo anti-tumour performance and effectively inhibited tumour growth in the tested model.

Pump mediated drug efflux is the key reason to result in the failure of chemotherapy. Herein, a novel star polymer β-CD-v-(PEG-β-PNIPAAm)7 consisting of a β-CD core, grafted with thermo-responsive poly(N-isopropylacrylamide) (PNIPAAm) and biocompatible poly(ethylene glycol) (PEG) in the multiple "V"-shaped arms is designed and further fabricated into supramolecular nanocarriers for drug resistant cancer therapy. The star polymer could encapsulate chemotherapeutics between β-cyclodextrin and anti-cancer drug via inclusion complex (IC). Furthermore, the temperature induced chain association of PNIPAAm segments facilitated the IC to form supramolecular nanoparticles at 37 °C, whereas the presence of PEG impart great stability to the self-assemblies. When incubated with MDR-1 membrane pump regulated drug resistant tumor cells, much higher and faster cellular uptake of the supramolecular nanoparticles were detected, and the enhanced intracellular retention of drugs could lead to significant inhibition of cell growth. Further in vivo evaluation showed high therapeutic efficacy in suppressing drug resistant tumor growth without a significant impact on the normal functions of main organs. This work signifies thermo-responsive supramolecular chemotherapy is promising in combating pump mediated drug resistance in both in vitro and in vivo models, which may be encouraging for the advanced drug delivery platform design to overcome drug resistant cancer.

A detailed understanding of chemotherapy is determined by the response of cell to the formation of the drug-target complex and its corresponding sudden or eventual cell death. However, visualization of this early but important process, encompassing the fast dynamics as well as complex network of molecular pathways, remains challenging. Herein, we report that the nanomechanical traction force is sensitive enough to reflect the early cellular response upon the addition of chemotherapeutical molecules in a real-time and noninvasive manner, due to interactions between chemotherapeutic drug and its cytoskeleton targets. This strategy has outperformed the traditional cell viability, cell cycle, cell impendence as well as intracellular protein analyses, in terms of fast response. Furthermore, by using the nanomechanical traction force as a nanoscale biophysical marker, we discover a cellular nanomechanical change upon drug treatment in a fast and sensitive manner. Overall, this approach could help to reveal the hidden mechanistic steps in chemotherapy and provide useful insights in drug screening. NRF (Natl Research Foundation, S’pore) Accepted version

Developing optical tumor imaging probes with minimal background noise is very important for its early detection of small lesions and accurate diagnosis of cancer. To overcome the bottleneck of low signal to noise ratio and sensitivity, it needs further improvement in fluorescent probe design and understanding of tumor development process. Recent reports reveal that lysosome's acidity in cancer cells can be below 4.5 with high Na+ /H+ exchange activity, which makes it an ideal target intracellular organelle for cancer diagnosis based on the variation of pH. Herein, a boron 2-(2'-pyridyl) imidazole complex derivative (BOPIM-N) is developed, with the ability to show a pH-activatable "OFF-ON" fluorescent switch by inhibiting twisted intramolecular charge transfer upon protonation at pH 3.8-4.5, which is studied for its selective viable cancer cell imaging ability in both in vitro and in vivo experiments. Interestingly, BOPIM-N can specifically emit green fluorescence in lysosomes of cancer cells, indicating its promising cancer cell specific imaging ability. More importantly, nanoformulated BOPIM-N probes can be specifically light-ON in tumor bearing site of nude mice with resolution up to cellular level, indicating its potential application in tumor diagnosis and precision medicine.

A tumor active targeting β-cyclodextrin based nanocarrier β-NC-OEI-SS-FA was designed by the modification of star shaped cationic derivatives β-NC-OEI with folic acid through a disulfide bond, to co-deliver chemotherapeutic paclitaxel and the Nur77 gene for overcoming Bcl-2 mediated non-pump resistance by an “enemy to friend” strategy for potential drug resistant cancer therapy.

The synthesis of a multiblock poly(ether ester urethane)s comprising poly(e-caprolactone), poly(ethylene glycol), and poly(propylene glycol) segments is described. We found that this polymer possessed a critical thermo-gelation concentration of 4wt%. Molecular characterization of the polymer was performed in terms of molecular weight determination, chemical composition elucidation and functional group determination using GPC, NMR, and FTIR. We carried out in vitro paclitaxel and doxorubicin release studies and demonstrated that sustained therapeutic release of about 2weeks can be obtained with this system. A nude mice model of tumor was developed and intratumoral injection of therapeutic-loaded thermo-gel demonstrated that PTX-loaded thermo-gel effectively inhibited the growth of tumors.

A large amount of evidence has demonstrated the revolutionary role of nanosystems in the screening and shielding of biological systems. The explosive development of interfacing bioentities with programmable nanomaterials has conveyed the intriguing concept of nano-bio interfaces. Here, recent advances in functional biointegrated devices through the precise programming of nano-bio interactions are outlined, especially with regard to the rational assembly of constituent nanomaterials on multiple dimension scales (e.g., nanoparticles, nanowires, layered nanomaterials, and 3D-architectured nanomaterials), in order to leverage their respective intrinsic merits for different functions. Emerging nanotechnological strategies at nano-bio interfaces are also highlighted, such as multimodal diagnosis or "theragnostics", synergistic and sequential therapeutics delivery, and stretchable and flexible nanoelectronic devices, and their implementation into a broad range of biointegrated devices (e.g., implantable, minimally invasive, and wearable devices). When utilized as functional modules of biointegrated devices, these programmable nano-bio interfaces will open up a new chapter for precision nanomedicine.

Three chelating-amino-functionalized lanthanide metal-organic frameworks, Y-DDQ, Dy-DDQ and Eu-DDQ, were synthesized with a flexible dicarboxylate ligand based on quinoxaline (H2DDQ = N, N′-dibenzoic acid-2,3-diaminoquinoxaline). The three-dimensional framework is constructed by the H2DDQ linkers connecting the zigzag ladders, showing a net of sra topology. In the structures, one kind of Ln(III) ions metal centers are six-coordinated and thus can potentially behave as open metal sites (OMSs), while the free chelating amino groups can act as free functional organic sites (FOSs). The N2 and Ar adsorption behaviors indicate that these Ln-DDQ exhibits stable microporous frameworks with high surface area after remove of the solvents. Owing to presence of OMSs and FOSs, these MOFs show good ability of CO2, dyes captures and Lewis acid catalyst for cyanosilylation reaction. In view of the existing FOSs in the framework, Pd NPs were immobilized onto the MOFs through graft interactions between free chelating amino groups and metal ions precursor using postsynthetic modification. The well dispersed Pd@Ln-DDQs exhibit efficient and recyclable catalytic reduction of 4-nitrophenol to 4-aminophenol and they can also act as an excellent catalyst for Suzuki-Miyaura cross-coupling reactions with the exposed Pd NPs.

Injectable thermogel to deliver chemotherapeutics in a minimally invasive manner and to achieve their long term sustained release at tumor sites to minimize side effects is attractive for chemotherapy and precision medicine, but its rational design remains a challenge. In this work, a copolymer with natural biodegradable poly[(R)-3-hydroxybutyrate] (PHB), hydrophilic poly(ethylene glycol), and temperature sensitive poly(propylene glycol) blocks linked by urethane linkages is designed to show thermogelling characteristics which are beneficial for minimally invasive injection and safe degradation. This thermogelling polymer possesses in vitro biocompatibility with very low cyto-toxicity in HEK293 cells. Furthermore, it is able to form the gel to achieve the controllable release of paclitaxel (PTX) and doxorubicin (DOX) by adjusting polymer concentrations. A rodent model of hepatocarcinoma has been performed to demonstrate the in vivo applications of this PHB-based thermogel. The drug-loaded thermogel has been intratumorally injected and both PTX-loaded and DOX-loaded thermogel have significantly slowed down tumor growth. This work represents the first time that injectable PHB thermogels have possessed good controllable release effect of chemotherapeutics against the in vivo model of tumors and will benefit various applications, including on-demand drug delivery and personalized medicine.

A new drug concentration meter is developed. In vivo drug release can be monitored precisely via a self-indicating drug delivery system consisting of a new aggregation-induced emission thermoresponsive hydrogel. By taking the advantage of a self-indicating system, one can easily detect the depletion of drugs, and reinject to maintain a dosage in the optimal therapeutic window. ASTAR (Agency for Sci., Tech. and Research, S’pore) MOE (Min. of Education, S’pore) Accepted version

Gold nanoparticles (AuNPs), with elegant thermal, optical, or chemical properties due to quantum size effects, may serve as unique species for therapeutic or diagnostic applications. It is worth mentioning that their small size also results in high surface activity, leading to significantly impaired stability, which greatly hinders their biomedical utilizations. To overcome this problem, various types of macromolecular materials are utilized to anchor AuNPs so as to achieve advanced synergistic effect by dispersing, protecting, and stabilizing the AuNPs in polymeric-Au hybrid self-assemblies. In this review, the most recent development of polymer-AuNP hybrid systems, including AuNPs@polymeric nanoparticles, AuNPs@polymeric micelle, AuNPs@polymeric film, and AuNPs@polymeric hydrogel are discussed with respect to their different synthetic strategies. These sophisticated materials with diverse functions, oriented toward biomedical applications, are further summarized into several active domains in the areas of drug delivery, gene delivery, photothermal therapy, antibacterials, bioimaging, etc. Finally, the possible approaches for future design of multifunctional polymer-AuNP hybrids by combining hybrid chemistry with biological interface science are proposed.

Effective delivery of therapeutic genes or small molecular drugs into macrophages is important for cell based immune therapy, but it remains a challenge due to the intracellular reactive oxygen species and endosomal degradation of therapeutics inside immune cells. In this report, the star-like amphiphilic biocompatible β-cyclodextrin-graft-(poly(e-caprolactone)-block-poly(2-(dimethylamino) ethyl methacrylate)x (β-CD-g-(PCL-b-PDMAEMA)x ) copolymer, consisting of a biocompatible cyclodextrin core, hydrophobic poly(e-caprolactone) PCL segments and hydrophilic PDMAEMA blocks with positive charge, is optimized to achieve high efficiency gene transfection with enhanced stability, due to the micelle formation by hydrophobic PCL segments. In comparison with lipofetamine, a currently popular nonviral gene carrier, β-CD-g-(PCL-b-PDMAEMA)x copolymer, shows better transfection efficiency of plasmid desoxyribose nucleic acid in RAW264.7 macrophages. More interestingly, this delivery platform by β-CD-g-(PCL-b-PDMAEMA)x not only shows low toxicity but also better dexamethasone delivery efficiency, which might indicate its great potential in immunotherapy.

Antiapoptotic Bcl-2 protein's upregulated expression is a key reason for drug resistance leading to failure of chemotherapy. In this report, a series of biocompatible amphiphilic cationic poly[(R)-3-hydroxybutyrate] (PHB)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) copolymer, comprising hydrophobic PHB block and cationic PDMAEMA block, is designed to codeliver hydrophobic chemotherapeutic paclitaxel and Bcl-2 converting gene Nur77/ΔDBD with enhanced stability, due to the micelle formation by hydrophobic PHB segment. This copolymer shows less toxicity but similar gene transfection efficiency to polyethyenimine (25k). More importantly, this codelivery approach by PHB-PDMAEMA leads to increased drug resistant HepG2/Bcl-2 cancer cell death, by increased expression of Nur77 proteins in the Bcl-2 present intracellular mitochondria. This work signifies for the first time that cationic amphiphilic PHB-b-PDMAEMA copolymers can be utilized for the drug and gene codelivery to drug resistant cancer cells with high expression of antiapoptosis Bcl-2 protein and the positive results are encouraging for the further design of codelivery platforms for combating drug resistant cancer cells.