Noncovalently particle-anchored cytokines with prolonged tumor retention safely elicit potent antitumor immunity.

Preclinical studies have shown that immunostimulatory cytokines elicit antitumor immune responses but their clinical use is limited by severe immune-related adverse events upon systemic administration. Here, we report a facile and versatile strategy for noncovalently anchoring potent Fc-fused cytokine molecules to the surface of size-discrete particles decorated with Fc-binding peptide for local administration. Following intratumoral injection, particle-anchored Fc cytokines exhibit size-dependent intratumoral retention.

Recent advances in enantioselective ring-opening polymerization and copolymerization.

Precisely controlling macromolecular stereochemistry and sequences is a powerful strategy for manipulating polymer properties. Controlled synthetic routes to prepare degradable polyester, polycarbonate, and polyether are of recent interest due to the need for sustainable materials as alternatives to petrochemical-based polyolefins. Enantioselective ring-opening polymerization and ring-opening copolymerization of racemic monomers offer access to stereoregular polymers, specifically enantiopure polymers that form stereocomplexes with improved physicochemical and mechanical properties.

Bayesian-optimization-assisted discovery of stereoselective aluminum complexes for ring-opening polymerization of racemic lactide.

Stereoselective ring-opening polymerization catalysts are used to produce degradable stereoregular poly(lactic acids) with thermal and mechanical properties that are superior to those of atactic polymers. However, the process of discovering highly stereoselective catalysts is still largely empirical. We aim to develop an integrated computational and experimental framework for efficient, predictive catalyst selection and optimization.

Recent Advances in Sequence-Controlled Ring-Opening Copolymerizations of Monomer Mixtures.

Transforming renewable resources into functional and degradable polymers is driven by the ever-increasing demand to replace unsustainable polyolefins. However, the utility of many degradable homopolymers remains limited due to their inferior properties compared to commodity polyolefins. Therefore, the synthesis of sequence-defined copolymers from one-pot monomer mixtures is not only conceptually appealing in chemistry, but also economically attractive by maximizing materials usage and improving polymers' performances.

Ganglioside GM3-Functionalized Reconstituted High-Density Lipoprotein (GM3-rHDL) as a Novel Nanocarrier Enhances Antiatherosclerotic Efficacy of Statins in apoE C57BL/6 Mice.

Previously, we found that exogenous ganglioside GM3 had an antiatherosclerotic efficacy and that its antiatherosclerotic efficacy could be enhanced by reconstituted high-density lipoprotein (rHDL). In this study, we hypothesized that GM3-functionalized rHDL (i.e.

Facile Tandem Copolymerization of -Carboxyanhydrides and Epoxides to Synthesize Functionalized Poly(ester--carbonates).

The synthesis of well-defined degradable block copolymers from mixtures of monomers is one of the foremost challenges in the sustainable plastics industry. For example, the currently available one-pot strategies for preparing poly(ester--carbonates)─which combine two commonly used degradable polymers─are energy- and material-intensive, requiring high-pressure CO gas and elevated temperatures. Here, we report an atom-economical, scalable method for block copolymerization of -carboxyanhydrides (OCAs) and epoxides to prepare functionalized poly(ester--carbonates) with high molecular weights (MWs) (>200 kDa) and narrow MW distributions ( < 1.

Enhanced Anti-Atherosclerotic Efficacy of pH-Responsively Releasable Ganglioside GM3 Delivered by Reconstituted High-Density Lipoprotein.

Recently, the atheroprotective role of endogenous GM3 and an atherogenesis-inhibiting effect of exogenous GM3 suggested a possibility of exogenous GM3 being recruited as an anti-atherosclerotic drug. This study seeks to endow exogenous GM3 with atherosclerotic targetability via reconstituted high-density lipoprotein (rHDL), an atherosclerotic targeting drug nanocarrier. Unloaded rHDL, rHDL loaded with exogenous GM3 at a low concentration (GM3-rHDL), and rHDL carrying GM3 at a relatively high concentration (GM3-rHDL) were prepared and characterized.

Resilient Poly(α-hydroxy acids) with Improved Strength and Ductility via Scalable Stereosequence-Controlled Polymerization.

Despite the degradability and biocompatibility of poly(α-hydroxy acids), their utility remains limited because their thermal and mechanical properties are inferior to those of commodity polyolefins, which can be attributed to the lack of side-chain functionality on the polyester backbone. Attempts to synthesize high-molecular-weight functionalized poly(α-hydroxy acids) from -carboxyanhydrides have been hampered by scalability problems arising from the need for an external energy source such as light or electricity. Herein, we report an operationally simple, scalable method for the synthesis of stereoregular, high-molecular-weight (>200 kDa) functionalized poly(α-hydroxy acids) by means of controlled ring-opening polymerization of -carboxyanhydrides mediated by a highly redox reactive manganese complex and a zinc-alkoxide.

Implantable optical fibers for immunotherapeutics delivery and tumor impedance measurement.

Immune checkpoint blockade antibodies have promising clinical applications but suffer from disadvantages such as severe toxicities and moderate patient-response rates. None of the current delivery strategies, including local administration aiming to avoid systemic toxicities, can sustainably supply drugs over the course of weeks; adjustment of drug dose, either to lower systemic toxicities or to augment therapeutic response, is not possible. Herein, we develop an implantable miniaturized device using electrode-embedded optical fibers with both local delivery and measurement capabilities over the course of a few weeks.

Photocatalyst-independent photoredox ring-opening polymerization of -carboxyanhydrides: stereocontrol and mechanism.

Photoredox ring-opening polymerization of -carboxyanhydrides allows for the synthesis of polyesters with precisely controlled molecular weights, molecular weight distributions, and tacticities. While powerful, obviating the use of precious metal-based photocatalysts would be attractive from the perspective of simplifying the protocol. Herein, we report the Co and Zn catalysts that are activated by external light to mediate efficient ring-opening polymerization of -carboxyanhydrides, without the use of exogenous precious metal-based photocatalysts.

Aliphatic Polyester-Based Materials for Enhanced Cancer Immunotherapy.

Poly(lactic acid) (PLA) and its copolymer, poly(lactic-co-glycolic acid) (PLGA), based aliphatic polyesters have been extensively used for biomedical applications, such as drug delivery system and tissue engineering, thanks to their biodegradability, benign toxicity, renewability, and adjustable mechanical properties. A rapidly growing field of cancer research, the development of therapeutic cancer vaccines or treatment modalities is aimed to deliver immunomodulatory signals that control the quality of immune responses against tumors. Herein, the progress and applications of PLA and PLGA are reviewed in delivering immunotherapeutics to treat cancers.

Nano-optoelectrodes Integrated with Flexible Multifunctional Fiber Probes by High-Throughput Scalable Fabrication.

Metallic nano-optoelectrode arrays can simultaneously serve as nanoelectrodes to increase the electrochemical surface-to-volume ratio for high-performance electrical recording and optical nanoantennas to achieve nanoscale light concentrations for ultrasensitive optical sensing. However, it remains a challenge to integrate nano-optoelectrodes with a miniaturized multifunctional probing system for combined electrical recording and optical biosensing in vivo. Here, we report that flexible nano-optoelectrode-integrated multifunctional fiber probes can have hybrid optical-electrical sensing multimodalities, including optical refractive index sensing, surface-enhanced Raman spectroscopy, and electrophysiological recording.

Functionalized Polyesters via Stereoselective Electrochemical Ring-Opening Polymerization of -Carboxyanhydrides.

Ring-opening polymerization is used to prepare polyesters with precisely controlled molecular weights, molecular weight distributions, and tacticities. Herein, we report a Co/Zn catalytic system that can be activated by an electrical current to mediate efficient ring-opening polymerization of enantiopure -carboxyanhydrides, allowing for the synthesis of isotactic functionalized polyesters with high molecular weights (>140 kDa) and narrow molecular weight distributions (/ < 1.1).

Isolated cell-bound membrane vesicles (CBMVs) as a novel class of drug nanocarriers.

Background: Cell-bound membrane vesicles (CBMVs) are a type of membrane vesicles different from the well-known extracellular vesicles (EVs). In recent years, the applications of EVs as drug delivery systems have been studied widely. A question may arise whether isolated CBMVs also have the possibility of being recruited as a drug delivery system or nanocarrier?

Methods: To test the possibility, CBMVs were isolated/purified from the surfaces of cultured endothelial cells, loaded with a putative antitumor drug doxorubicin (Dox), and characterized.

Reprogramming the microenvironment with tumor-selective angiotensin blockers enhances cancer immunotherapy.

Cancer-associated fibroblasts (CAFs) can either suppress or support T lymphocyte activity, suggesting that CAFs may be reprogrammable to an immunosupportive state. Angiotensin receptor blockers (ARBs) convert myofibroblast CAFs to a quiescent state, but whether ARBs can reprogram CAFs to promote T lymphocyte activity and enhance immunotherapy is unknown. Moreover, ARB doses are limited by systemic adverse effects such as hypotension due to the importance of angiotensin signaling outside tumors.

Living Ring-Opening Polymerization of -Carboxyanhydrides: The Search for Catalysts.

Biodegradable poly(α-hydroxy acids) can be synthesized by means of ring-opening polymerization (ROP) of -carboxyanhydrides (OCAs). Numerous catalysts have been developed to control the living polymerization of OCAs. Here we review the rationale for the use of OCA, the desirable features for and important attributes of catalysts for the ROP of OCAs, and specific examples that have been developed.

Stereoselective photoredox ring-opening polymerization of O-carboxyanhydrides.

Biodegradable polyesters with various tacticities have been synthesized by means of stereoselective ring-opening polymerization of racemic lactide and β-lactones but with limited side-chain groups. However, stereoselective synthesis of functional polyesters remains challenging from O-carboxyanhydrides that have abundant pendant side-chain functional groups. Herein we report a powerful strategy to synthesize stereoblock polyesters by stereoselective ring-opening polymerization of racemic O-carboxyanhydrides with the use of photoredox Ni/Ir catalysts and a selected Zn complex with an achiral ligand.

BaTiO-core Au-shell nanoparticles for photothermal therapy and bimodal imaging.

Unlabelled: We report sub-100 nm metal-shell (Au) dielectric-core (BaTiO) nanoparticles with bimodal imaging abilities and enhanced photothermal effects. The nanoparticles efficiently absorb light in the near infrared range of the spectrum and convert it to heat to ablate tumors. Their BaTiO core, a highly ordered non-centrosymmetric material, can be imaged by second harmonic generation, and their Au shell generates two-photon luminescence.

Controlled Photoredox Ring-Opening Polymerization of O-Carboxyanhydrides Mediated by Ni/Zn Complexes.

Here, we describe an effective protocol that combines photoredox Ni/Ir catalysis with the use of a Zn-alkoxide for efficient ring-opening polymerization, allowing for the synthesis of isotactic poly(α-hydroxy acids) with expected molecular weights (>140 kDa) and narrow molecular weight distributions (Mw/Mn < 1.1). This ring-opening polymerization is mediated by Ni and Zn complexes in the presence of an alcohol initiator and a photoredox Ir catalyst, irradiated by a blue LED (400 - 500 nm).

Emerging strategies in near-infrared light triggered drug delivery using organic nanomaterials.

Near-infrared light has significant advantages for light-triggered drug delivery systems within deep tissues. The use of inorganic nanomaterials raises concern over their long-term in vivo toxicities. Here we will highlight emerging near-infrared light-triggered drug delivery using organic nanomaterials, as well as new photocleavage reactions mediated by near-infrared light.

Therapeutic Action of Honokiol on Postoperative Ileus via Downregulation of iNOS Gene Expression.

Postoperative ileus is a common complication after intra-abdominal surgery. Nitric oxide produced by macrophages in the inflamed gastrointestinal tract plays a crucial role in the pathogeny of postoperative ileus. Honokiol, extracted from the bark of Magnolia spp.

Controlled Photoredox Ring-Opening Polymerization of O-Carboxyanhydrides.

Poly(α-hydroxy acids) are important biodegradable polymers with wide applications. Attempts to synthesize them from O-carboxyanhydrides with pendant functional groups by various methods, including methods involving organocatalysts or organometallics, have been plagued by uncontrolled polymerization, including epimerization for some monomers, which hampers the preparation of stereoregular high-molecular-weight polymers. Herein we describe an effective protocol that combines photoredox Ni/Ir catalysis with the use of a Zn-alkoxide for efficient ring-opening polymerization, allowing for the synthesis of isotactic polyesters with expected molecular weights (>140 kDa) and narrow molecular weight distributions (M/M < 1.

Anticancer nanoparticulate polymer-drug conjugate.

We review recent progress in polymer-drug conjugate for cancer nanomedicine. Polymer-drug conjugates, including the nanoparticle prepared from these conjugates, are designed to release drug in tumor tissues or cells in order to improve drugs' therapeutic efficacy. We summarize general design principles for the polymer-drug conjugate, including the synthetic strategies, the design of the chemical linkers between the drug and polymer in the conjugate, and the in vivo drug delivery barriers for polymer-drug conjugates.

Controlled Ring-Opening Polymerization of O-Carboxyanhydrides Using a β-Diiminate Zinc Catalyst.

Recently O-carboxyanhydrides (OCAs) have emerged as a class of viable monomers which can undergo ring-opening polymerization (ROP) to prepare poly(α-hydroxyalkanoic acid) with functional groups that are typically difficult to achieve by ROP of lactones. Organocatalysts for the ROP of OCAs, such as dimethylaminopyridine (DMAP), may induce undesired epimerization of the α-carbon atom in polyesters resulting in the loss of isotacticity. Herein, we report the use of (BDI-IE)Zn(OCH(CH )COOCH ) ((BDI)Zn-1, (BDI-IE)=2-((2,6-diethylphenyl)amino)-4-((2,6-diisopropylphenyl)imino)-2-pentene), for the controlled ROP of various OCAs without epimerization.

Treatment of otitis media by transtympanic delivery of antibiotics.

Otitis media is the most common reason U.S. children receive antibiotics.