Bacterial-infections are mostly due to bacteria in their biofilm-mode of growth. Nanotechnology-based antimicrobials possess excellent potential in biofilm-infection control, overcoming the biological barriers of biofilms.

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.

drugs, antimicrobials, proteins delivery, and tissue repair. PBAEs are synthesized via a one-pot Michael addition of amines to acrylates (Scheme 1) without the production of any byproducts. The hydrolytically degradable ester bonds provide PBAEs with excellent biodegradability, thus reducing the cytotoxicity caused by necrosis and apoptosis. [5] The tertiary amine groups can electrostatically interact with negatively charged gene [6] or therapeutics [7] to form nanocomposites. Besides, the amino groups undergo phase transition upon the charge of surrounding pH, possessing pH-responsive and charge reversible properties, [8,9] and those properties make the PBAEs promising candidates for controlled and programmable release. [10] The key factor of PBAEs is their potential for structural diversity due to the combination of different monomers. [4] In addition, PBAEs are compatible with a wide range of polymers, for instance, poly(ethylene glycol) (PEG), [11] poly (lactic acid) (PLA), [12] and poly(ε-caprolactone) (PCL) [13] to form block copolymers. Taken together, these cases demonstrated the versatility of the PBAEs in the modification of their physical, chemical, and mechanical properties. In this review, we emphasize all types of PBAE-based formulations, namely, nanocomposites, micelles, hydrogels, and films for therapeutics delivery and tissue repair applications. MonomersDiverse acrylates (A) were employed in PBAE synthesis, as shown and classified in Figure 1. The functional groups like alkyl, aryl, and ester groups (A1-A14) are hydrophobic, which Poly(β-amino ester) (abbreviated as PBAE or PAE) refers to a polymer synthesized from an acrylate and an amine by Michael addition and has properties inherent to tertiary amines and esters, such as pH responsiveness and biodegradability. The versatility of building blocks provides a library of polymers with miscellaneous physicochemical and mechanical properties. When used alone or together with other materials, PBAEs can be fabricated into different formulations in order to fulfill various requirements in drug delivery (for instance, gene, anticancer drugs, and antimicrobials delivery) and natural complex mimicry (nanochaperones). This progress report discusses the recent developments in design, synthesis, formulations, and applications of PBAEs in biomedical fields and provides a perspective view for the future of the PBAEs.

Strong Mn−Mn coupling interactions (dipole− dipole and spin−exchange), predominantly determined by statistically and apparently short Mn•••Mn distances in traditional heavily Mn 2+ -doped semiconductors, can promote energy transfer within randomly positioned and close-knit Mn 2+ pairs. However, the intrinsic mechanism on controlling Mn 2+ emission efficiency is still elusive due to the lack of precise structure information on local tetrahedrally coordinated Mn 2+ ions. Herein, a group of Mn 2+containing metal−chalcogenide open frameworks (MCOFs), built from [Mn 4 In 16 S 35 ] nanoclusters (denoted T4-MnInS) with a precise [Mn 4 S] configuration and length-variable linkers, were prepared and selected as unique models to address the abovementioned issues. MCOF-5 and MCOF-6 that contained a symmetrical [Mn 4 S] core with a D 2d point group and relatively long Mn•••Mn distance (∼3.9645 Å) exhibited obvious red emission, while no room-temperature PL emission was observed in MCOF-7 that contained an asymmetric [Mn 4 S] configuration with a C 1 point group and relatively short Mn•••Mn distance (∼3.9204 Å). The differences of Mn−Mn dipole−dipole and spin−exchange interactions were verified through transient photoluminescent spectroscopy, electron spin resonance (ESR), and magnetic measurements. Compared to MCOF-5 and MCOF-6 showing a narrower/stronger ESR signal and longer decay lifetime of microseconds, MCOF-7 displayed a much broader/weaker ESR signal and shorter decay lifetime of nanoseconds. The results demonstrated the dominant role of distance-directed Mn−Mn dipole−dipole interactions over symmetry-directed spin−exchange interactions in modulating PL quenching behavior of Mn 2+ emission. More importantly, the reported work offers a new pathway to elucidate Mn 2+ -site-dependent photoluminescence regulation mechanism from the perspective of atomically precise nanoclusters.

Stimuli-sensitive hydrogels are ideal candidates for biomedical and bioengineering purposes, although applications of hydrogels may be limited, due in part to the limited choice of suitable materials for constructing hydrogels, the complexity in the synthesis of the source materials, and the undesired fast-then-slow drug-release behaviors of usual hydrogels. Herein, we describe the fabrication of a new supramolecular guanosine (G)-quadruplex hydrogel by multicomponent self-assembly of endogenous guanosine (G), 2-formylboronic acid (2-FPBA), and tris(2-aminoethyl)amine (TAEA) in the presence of KCl in an easy and convenient way. The features of the G-quadruplex hydrogel include (1) versatility and commercial availability of building blocks with different functions, (2) dynamic iminoboronate bonds with pH and glucose responsiveness, and (3) zero-order drug-release behavior because of the superficial peel-off of the hydrogel in response to stimuli. The structure, morphology, and properties of the G-quadruplex hydrogel were well-characterized, and satisfactory zero-order drug release was successfully achieved. This kind of supramolecular G-quadruplex hydrogels may find applications in biological fields.

The mucus layer and cell membrane are two major barriers against pulmonary siRNA delivery. Commonly used polycationic gene vectors can hardly penetrate the mucus layer due to the adsorption of mucin glycoproteins that trap and destabilize the polyplexes. Herein, guanidinated and fluorinated bifunctional helical polypeptides were developed to synchronizingly overcome these two barriers. The guanidine domain and α-helix facilitated trans-membrane siRNA delivery into macrophages, whereas fluorination of the polypeptides dramatically enhanced the mucus permeation capability by ∼240 folds, because incorporated fluorocarbon segments prevented adsorption of mucin glycoproteins onto polyplexes surfaces. Thus, when delivering TNF-α siRNA intratracheally, the top-performing polypeptide P7F7 provoked highly efficient gene knockdown by ∼96% at 200 μg/kg siRNA and exerted pronounced anti-inflammatory effect against acute lung injury. This study thus provides an effective strategy for transmucosal gene delivery, and it also renders promising utilities for the noninvasive, localized treatment of inflammatory pulmonary diseases.

Black phosphorus (BP) as a novel class of two-dimension (2D) materials has recently attracted enormous attention as a result of its unique physical and chemical features. The remarkably strong light-matter interaction and tunable direct band-gap at a wide range make it an ideal candidate especially in the mid-infrared wavelength region as the saturable absorber (SA). In this paper, the simple and effective liquid phase exfoliation (LPE) method was used to fabricate BP. By introducing the same BP SA into two specifically designed rare earth ions doped fluoride fiber lasers at mid-infrared wavebands, Q-switching with the pulse energy of 4.93 μJ and mode-locking with the pulse duration of 8.6 ps were obtained, respectively. The operation wavelength of ~2970 nm for generated pulse is the reported longest wavelength for BP SA based fiber lasers.

Bacterial infections are mostly due to bacteria in their biofilm mode-ofgrowth, 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 proto porphyrin 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 lightactivatable antimicrobials constitute a much-needed alternative to current antibiotic therapies.