A Hybrid Alloying Nanozyme-Glutathione Inhibitor Co-Delivery System Initiates a Dual-Disruption on Cancer Redox Homeostasis.

Altered redox homeostasis has long been observed in cancer cells, which can be exploited for therapeutic benefits. However, reactive oxygen species (ROS) pleiotropy coupling with reductive adaptation in cancer cells poses a formidable challenge for redox dyshomeostasis-based cancer therapy. Herein, a AuPd alloying nanozyme-glutathione (GSH) biosynthesis inhibitor co-delivery system (B-BMES) is developed using dendritic SiO as a matrix to target cancer redox homeostasis.

A Poly(amino acid)-Based Nanomedicine Strategy: Telomere-Telomerase Axis Targeting and Magnetic Resonance Imaging in Hepatocellular Carcinoma Treatment.

Targeting telomere maintenance has emerged as a promising strategy for hepatocellular carcinoma (HCC) treatment. However, given the duality of the telomere-telomerase axis in telomere maintenance, a comprehensive strategy is urgently needed. Herein, we develop a poly(amino acid) (D-PAAs)-based strategy for spatiotemporal codelivery of telomerase inhibitor, BIBR1523, and AKT inhibitor, isobavachalcone.

Integrating Liquification of the Gelated Tumor Interstitium around Nanomedicines with Biconditional GD2-Targeting for Precise and Safe Chemotherapy.

The quick diffusion of nanomedicines in the polysaccharide-gel-filling tumor interstitium and precise active targeting are two major obstacles that have not yet been overcome. Here, a poly(L-glutamyl-L-lysine(EK) (p(EK))-camouflaged, doxorubicin (Dox)-conjugated nanomedicine is developed to demonstrate the underlying mechanism of zwitterionic shell in synchronous barrier-penetration and biconditional active targeting. The zwitterionic p(EK) shell liquifies its surrounding water molecules in the polysaccharide gel of tumor interstitium, leading to five times faster diffusion than the pegylated Doxil with similar size in tumor tissue.

An Engineered Design of Self-Assembly Nanomedicine Guided by Molecular Dynamic Simulation for Photodynamic and Hypoxia-Directed Therapy.

To overcome the hypoxia barrier in tumor therapy, a hypoxia-activated prodrug of docetaxel (DTX-PNB) was synthesized and self-assembled with indocyanine green (ICG), forming a combination nanomedicine ISDNN. With the guidance of molecular dynamic simulation, the ISDNN construction could be accurately controlled, achieving uniform size distribution and high drug loading up to 90%. Within the hypoxic tumor environment, ISDNN exerted ICG-mediated photodynamic therapy and aggravated hypoxia to boost DTX-PNB activation for chemotherapy, enabling enhanced antitumor efficacy.

Hyperthermia-induced stellate cell deactivation to enhance dual chemo and pH-responsive photothermal therapy for pancreatic cancers.

For pancreatic ductal adenocarcinoma (PDAC) treatment, the deactivation of pancreatic stellate cells (PSCs) by blocking the transforming growth factor β (TGF-β) pathway is a promising strategy to inhibit stroma, enhance drug penetration, and greatly amplify chemotherapeutic efficacy. It is known that photothermal therapy (PTT) locally depletes stroma and enhances permeability but whether and how PTT reacts in the molecular pathway to induce PSC deactivation in PDAC has rarely been investigated so far. Herein, C-G NPs are synthesized by loading both acid-responsive photothermal molecules and gemcitabine for investigating both the combinatory chemophotothermal therapy and the interaction between the PTT and TGF-β pathway in PDAC.

NIR-II and visible fluorescence hybrid imaging-guided surgery via aggregation-induced emission fluorophores cocktails.

Fluorescence imaging-guided surgery is one of important techniques to realize precision surgery. Although second near-infrared window (NIR-II) fluorescence imaging has the advantages of high resolution and large penetration depth in surgical navigation, its major drawback is that NIR-II images cannot be detected by our naked eyes, which demands a high hand-eye coordination for surgeons and increases the surgical difficulty. On the contrary, visible fluorescence can be observed by our naked eyes but has poor penetration.

Metabolically engineered bacteria as light-controlled living therapeutics for anti-angiogenesis tumor therapy.

A living therapeutic system based on attenuated Salmonella was developed via metabolic engineering using an aggregation-induced emission (AIE) photosensitizer MA. The engineered bacteria could localize in the tumor tissues and continue to colonize and express exogenous genes. Under light irradiation, the encoded VEGFR2 gene was released and expressed in tumor tissues, which can suppress angiogenesis induced by a T cell-mediated autoimmune response and inhibit tumor growth.

Chitosan-derived nanoparticles impede signal transduction in T790M lung cancer therapy.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treated patients ultimately develop disease progression, about 50% of which are involved in the emergence of a p.Thr790Met (T790M) mutation acquiring drug resistance. In order to solve the aforementioned problem, a therapeutic nanoparticles DGA is developed to overcome EGFR-T790M resistance downstream anti-apoptotic signal transduction blocking by a combination with persuading mitochondrial dysfunction and inhibiting miRNA expression.

Co-Crystals of Resveratrol and Polydatin with L-Proline: Crystal Structures, Dissolution Properties, and In Vitro Cytotoxicities.

Resveratrol (RSV) and polydatin (PD) have been widely used to treat several chronic diseases, such as atherosclerosis, pulmonary fibrosis, and diabetes, among several others. However, their low solubility hinders their further applications. In this work, we show that the solubility of PD can be boosted via its co-crystallization with L-proline (L-Pro).

In Vitro Anticancer Activity of Nanoformulated Mono- and Di-nuclear Pt Compounds.

Nanoformulations of mononuclear Pt complexes cis-PtCl (PPh ) (1), [Pt(PPh ) (L-Cys)] ⋅ H O (3, L-Cys=L-cysteinate), trans-PtCl (PPh PhNMe ) (4; PPh PhNMe =4-(dimethylamine)triphenylphosphine), trans-PtI (PPh PhNMe ) (5) and dinuclear Pt cluster Pt (μ-S) (PPh ) (2) have comparable cytotoxicity to cisplatin against murine melanoma cell line B16F10. Masking of these discrete molecular entities within the hydrophobic core of Pluronic® F-127 significantly boosted their solubility and stability, ensuring efficient cellular uptake, giving in vitro IC values in the range of 0.87-11.

Hydrogen Bonds, Topologies, Energy Frameworks and Solubilities of Five Sorafenib Salts.

Sorafenib (Sor) is an oral multi-kinase inhibitor, but its water solubility is very low. To improve its solubility, sorafenib hydrochloride hydrate, sorafenib hydrobromide and sorafenib hydrobromide hydrate were prepared in the mixed solvent of the corresponding acid solution, and tetrahydrofuran (THF). The crystal structures of sorafenib hydrochloride trihydrate (Sor·HCl.

Impact of Crystal Habit on the Dissolution Rate and In Vivo Pharmacokinetics of Sorafenib Tosylate.

The dissolution rate is the rate-limiting step for Biopharmaceutics Classification System (BCS) class II drugs to enhance their in vivo pharmacokinetic behaviors. There are some factors affecting the dissolution rate, such as polymorphism, particle size, and crystal habit. In this study, to improve the dissolution rate and enhance the in vivo pharmacokinetics of sorafenib tosylate (Sor-Tos), a BCS class II drug, two crystal habits of Sor-Tos were prepared.

Structural Insights into the Host-Guest Complexation between β-Cyclodextrin and Bio-Conjugatable Adamantane Derivatives.

Understanding the host-guest chemistry of α-/β-/γ- cyclodextrins (CDs) and a wide range of organic species are fundamentally attractive, and are finding broad contemporary applications toward developing efficient drug delivery systems. With the widely used β-CD as the host, we herein demonstrate that its inclusion behaviors toward an array of six simple and bio-conjugatable adamantane derivatives, namely, 1-adamantanol (adm-1-OH), 2-adamantanol (adm-2-OH), adamantan-1-amine (adm-1-NH), 1-adamantanecarboxylic acid (adm-1-COOH), 1,3-adamantanedicarboxylic acid (adm-1,3-diCOOH), and 2-[3-(carboxymethyl)-1-adamantyl]acetic acid (adm-1,3-diCHCOOH), offer inclusion adducts with diverse adamantane-to-CD ratios and spatial guest locations. In all six cases, β-CD crystallizes as a pair supported by face-to-face hydrogen bonding between hydroxyl groups on C2 and C3 and their adjacent equivalents, giving rise to a truncated-cone-shaped cavity to accommodate one, two, or three adamantane derivatives.

Cyclodextrin-based host-guest complexes loaded with regorafenib for colorectal cancer treatment.

The malignancy of colorectal cancer (CRC) is connected with inflammation and tumor-associated macrophages (TAMs), but effective therapeutics for CRC are limited. To integrate therapeutic targeting with tumor microenvironment (TME) reprogramming, here we develop biocompatible, non-covalent channel-type nanoparticles (CNPs) that are fabricated through host-guest complexation and self-assemble of mannose-modified γ-cyclodextrin (M-γ-CD) with Regorafenib (RG), RG@M-γ-CD CNPs. In addition to its carrier role, M-γ-CD serves as a targeting device and participates in TME regulation.

Enhancing the Physiochemical Properties of Puerarin via L-Proline Co-Crystallization: Synthesis, Characterization, and Dissolution Studies of Two Phases of Pharmaceutical Co-Crystals.

Puerarin (PUE) is a Chinese traditional medicine known to enhance glucose uptake into the insulin cells to downregulate the blood glucose levels in the treatment of type II diabetes. Nevertheless, the bioavailability of pristine PUE is limited due to its poor solubility and low intestinal permeability. In this work, we demonstrate that the solubility of PUE can be significantly enhanced via its co-crystallization with L-Proline (PRO).

Investigation of Solubility Behavior of Canagliflozin Hydrate Crystals Combining Crystallographic and Hirshfeld Surface Calculations.

Canagliflozin (CG) was a highly effective, selective and reversible inhibitor of sodium-dependent glucose co-transporter 2 developed for the treatment of type 2 diabetes mellitus. The crystal structure of CG monohydrate (CG-HO) was reported for the first time while CG hemihydrate (CG-Hemi) had been reported in our previous research. Solubility and dissolution rate results showed that the solubility of CG-Hemi was 1.

On the Single-Crystal Structure of Tenofovir Alafenamide Mono-Fumarate: A Metastable Phase Featuring a Mixture of Co-Crystal and Salt.

Tenofovir alafenamide (TAF) is a prodrug of tenofovir as a potent nucleotide reverse transcriptase inhibitor. It serves as the key component of Genvoya for the first-line treatment of human immunodeficiency virus infection (HIV) and is the active component of Vemlidy for the treatment of chronic hepatitis B. Vemlidy is also a monotherapeutic regimen formulated as TAF hemifumarate (; TAF:fumarate = 2:1).

Tumor-triggered personalized microRNA cocktail therapy for hepatocellular carcinoma.

As one of the most malignant primary cancers, hepatocellular carcinoma (HCC) still lacks an efficient therapeutic strategy to date. Here, we developed a polymer-based nanoplatform PEI-βCD@Ad-CDM-PEG (PCACP) for functional microRNA (miRNA) therapy. PCACP exhibits excellent stability in physiological solutions, but sensitive PEG detachment and size transformation in an acidic tumor environment due to the breakdown of pH-responsive linkages, promoting tumor penetration and cellular uptake of nanoparticles, further facilitating transfection efficiency due to the proton sponge effect of polycations.

Design and tuning of ionic liquid-based HNO donor through intramolecular hydrogen bond for efficient inhibition of tumor growth.

Developing ionic liquid (IL) drugs broaden new horizons in pharmaceuticals. The tunable nature endows ILs with capacity to delivery active ingredients. However, the tunability is limited to screen ionic components, and none realizes the kinetic tuning of drug release, which is a key challenge in the design of IL drugs.

Montmorillonite-Enveloped Zeolitic Imidazolate Framework as a Nourishing Oral Nano-Platform for Gastrointestinal Drug Delivery.

Oral administration of medicine faces physiological constraints imposed by the gastrointestinal tract (GIT) and simultaneously causes irritation to GI mucosa, which motivates us to pursue the innovation of a GI drug delivery system. Inspired by the mucosa-nutrient functions of Zinc element and smectite clay, a montmorillonite (MMT)-enveloped zeolitic imidazolate framework (M-ZIF-8) is developed in a successive one-pot fabrication of ZIF-8 encapsulated medicine, and followed MMT coating to yield a core-shell nanoplatform for GI drug delivery. ZIF-8 encapsulated medicines can maintain their intrinsic structure, and MMT layer potentiates mucous-adhesion and optimizes medicine release.

AIEgen-Lipid Conjugate for Rapid Labeling of Neutrophils and Monitoring of Their Behavior.

Studies on neutrophil-based nanotherapeutic engineering have shown great potentials in treating infection and inflammation disorders. Conventional neutrophil labeling methods are time-consuming and often result in undesired contamination and activation since neutrophils are terminal-differentiated cells with a half-life span of only 7 h. A simple, fast, and biocompatible strategy to construct engineered neutrophils is highly desirable but remains difficult to achieve.