Supramolecular chitin-based hydrogels with self-adapting and fast-degradation properties for enhancing wound healing.

Due to the features of high porosity, high water content, and tunable viscoelasticity, hydrogels have attracted numerous attentions in the promotion of wound closure. However, the lack of abilities to adapt the wounds of complex shapes and prevent postoperative adhesion limits their therapeutic outcomes in wound healing. To address the above challenges, the supramolecular chitin-based (SMCT) hydrogels are created via the host-guest pre-assembly strategy of β-cyclodextrin (βCD) and adamantane (Ad).

pH-triggered dynamic erosive small molecule chlorambucil nano-prodrugs mediate robust oral chemotherapy.

Currently, the dynamic erosive small molecule nano-prodrug is of great demand for oral chemotherapy, owing to its precise structure, high drug loading and improved oral bioavailability via overcoming various physiologic barriers in gastrointestinal tract, blood circulation and tumor tissues compared to other oral nanomedicines. Herein, this work highlights the successful development of pH-triggered dynamic erosive small molecule nano-prodrugs based on significant pH changes, which are synthesized via amide reaction between chlorambucil and star-shaped ortho esters. The precise nano-prodrugs exhibit extraordinarily high drug loading (68.

The mechanism of trans-δ-viniferin inhibiting the proliferation of lung cancer cells A549 by targeting the mitochondria.

Trans-δ-viniferin (TVN), as a natural extract, is a resveratrol dimer with attractive biological activities, particularly its anti-tumor character. However, the mechanism of TVN interfering with cancerous proliferation has not been fully understood. Herein in this study, we found that TVN could trigger cancerous mitochondrial membrane potential (ΔΨm) reduction, with intracellular reactive oxidative species (ROS) level increasing, leading to apoptosis, which makes TVN a promising candidate for lung cancer cells A549 treatment.

Dynamic crosslinked polymeric nano-prodrugs for highly selective synergistic chemotherapy.

To achieve highly selective synergistic chemotherapy attractive for clinical translation, the precise polymeric nano-prodrugs (PPD-NPs) were successfully constructed via the facile crosslinking reaction between pH-sensitive poly(ortho ester)s and reduction-sensitive small molecule synergistic prodrug (Pt(IV)-1). PPD-NPs endowed the defined structure and high drug loading of cisplatin and demethylcantharidin (DMC). Moreover, PPD-NPs exhibited steady long-term storage and circulation via the crosslinked structure, suitable negative potentials and low critical micelle concentration (CMC), improved selective tumour accumulation and cellular internalization via dynamic size transition and surficial amino protonation at tumoural extracellular pH, promoted efficient disintegration and drug release at tumoural intracellular pH/glutathione, and enhanced cytotoxicity via the synergistic effect between cisplatin and DMC with the feed ratio of 1:2, achieving significant tumour suppression while decreasing the side effects.

Construction of multifunctional mesoporous silicon nano-drug delivery system and study of dual sensitization of chemo-photodynamic therapy in vitro and in vivo.

This study was conducted to construct a multifunctional nanodrug delivery system (NDDS) to deplete glutathione (GSH) in tumor cells and amplify oxidative stress, enhancing the synergistic effect of chemotherapy and photodynamic therapy (PDT). l-Buthionine-sulfoximine (BSO) and chlorin e6 (Ce6) were loaded into mesoporous silicon nanoparticles (MSN), and then MSN were modified with oxidized hyaluronic acid (OHA) as a pore-blocking agent. Cisplatin (Pt(II)) was further loaded by a coordination reaction with carboxyl groups in OHA to yield a multifunctional NDDS (denoted as MSN@OHA-Ce6/BSO/Pt).

Dynamic carboxymethyl chitosan-based nano-prodrugs precisely mediate robust synergistic chemotherapy.

Currently, the polysaccharide-based nano-prodrug crosslinked by stimuli-responsive synergetic prodrug is of great demand, owing to its excellent stability, synergetic effect and tumor selectivity, and circumventing the dilemma of dose-limiting toxicity and immunogenicity induced by that crosslinked or grafted via a single drug. Herein, the dynamic carboxymethyl chitosan (CMCS)-based nano-prodrugs with precise structure were facilely fabricated, via crosslinking reaction between CMCS and water-soluble synergistic small molecule prodrug (cisplatin-demethylcantharidin conjugate) and further stabilization by glutaraldehyde. The pH/glutathione (GSH)-responsive double-crosslinked structure endowed the nano-prodrugs with long-term storge and circulation stability at physiological pH, and dynamic transitions at tumor sites including extracellular surface amino protonation and intracellular efficient drug release, which promoted selective tumor accumulation and synergistic cytotoxicity, therefore achieving robust tumor suppression while decreasing side effects.

Carrier-free prodrug nanoparticles based on lonidamine and cisplatin for synergistic treatment of breast cancer.

Herein, we combined a derivative of cisplatin (CP) and the chemosensitizer lonidamine (LND) to design an amphiphilic prodrug, in which the ratio of LND to cisplatin was fixed at 2:1. Diaminedichlorodihydroxyplatinum (DH-CP) is a hydrophilic cisplatin derivative. Due to its appropriate amphiphilicity, this prodrug could self-assemble into stable nanoparticles (denoted as LNP-NPs).

Carrier-free prodrug nanoparticles based on dasatinib and cisplatin for efficient antitumor .

Carrier-free drug self-delivery systems consisting of amphiphilic drug-drug conjugate (ADDC) with well-defined structure and nanoscale features have drawn much attention in tumor drug delivery. Herein, we report a simple and effective strategy to prepare ADDC using derivatives of cisplatin (CP) and dasatinib (DAS), which further self-assembled to form reduction-responsive nanoparticles (CP-DDA NPs). DAS was modified with succinic anhydride and then connected with CP derivative by ester bonds.

Self-assembled ternary hybrid nanodrugs for overcoming tumor resistance and metastasis.

Traditional chemotherapy exhibits a certain therapeutic effect toward malignant cancer, but easily induce tumor multidrug resistance (MDR), thereby resulting in the progress of tumor recurrence or metastasis. In this work, we deigned ternary hybrid nanodrugs (PEI/DOX@CXB-NPs) to simultaneously combat against tumor MDR and metastasis. results demonstrate this hybrid nanodrugs could efficiently increase cellular uptake at pH 6.

pH-triggered small molecule nano-prodrugs emulsified from tryptamine-cinnamaldehyde twin drug for targeted synergistic glioma therapy.

Chemotherapy fails to achieve an ideal gliomas therapy due to the limited delivery of chemotherapeutics across the blood brain barrier (BBB), difficult accumulation of drugs in the gliomas area, and off-target toxicity. Herein, the pH-triggered small molecule nano-prodrugs (Try-CA-NPs) emulsified from hydrophobic tryptamine (Try)-cinnamaldehyde (CA) twin drug were successfully prepared through a facile method. Try-CA-NPs exhibited long-term storage and circulation stability.

pH-sensitive and tumor-targeting nanogels based on ortho ester-modified PEG for improving the in vivo anti-tumor efficiency of doxorubicin.

In this study, we aim to develop the pH-sensitive and tumor-targeting nanogels based on the co-polymerization of three terminal allyl-functionalized components, including ortho ester-conjugated mPEG (mPEG-MOE), ortho ester crosslinker (OEAM) and phenylboronic acid (APBA). The hybrid nanogels displayed a typical spherical structure with a diameter around 200 nm observed by dynamic light scattering (DLS) and scanning electron microscopy (SEM). The prepared nanogels possessed a good stability in neutral conditions, while displayed pH-triggered drug release profiles.

Acid-sensitive and L61-crosslinked hyaluronic acid nanogels for overcoming tumor drug-resistance.

Low intracellular drugs concentration is one of the main representations of multidrug resistance (MDR), which often results in a weak or failed chemotherapy on cancer treatment. Herein, an acid-sensitive and pluronic L61-linked hyaluronic acid nanogels (HA-L61OE/NGs) were developed for solving this problem. The nanogels could well hold more drugs under neutral condition, while triggering efficiently drugs release (61.

Glucose-Targeted Hydroxyapatite/Indocyanine Green Hybrid Nanoparticles for Collaborative Tumor Therapy.

Nanoscale hydroxyapatite (nHA) is considered as a promising drug carrier or therapeutic agent against malignant tumors. But the strong agglomeration tendency and lack of active groups seriously hamper their usage . To address these issues, we fabricated an organic-inorganic hybrid nanosystem composed of poly(acrylic acid) (PAA), nHA, and indocyanine green (ICG), and further modified with glucose to give a targeting nanosystem (GA@HAP/ICG-NPs).

pH-sensitive micelles self-assembled from star-shaped TPGS copolymers with ortho ester linkages for enhanced MDR reversal and chemotherapy.

TPGS approved by FDA can be used as a P-gp inhibitor to effectively reverse multi-drug resistance (MDR) and as an anticancer agent for synergistic antitumor effects. However, the comparatively high critical micelle concentration (CMC), low drug loading (DL) and poor tumor target limit its further clinical application. To overcome these drawbacks, the pH-sensitive star-shaped TPGS copolymers were successfully constructed via using pentaerythritol as the initial materials, ortho esters as the pH-triggered linkages and TPGS active-ester as the terminated MDR material.

Lactobionic acid-modified phycocyanin nanoparticles loaded with doxorubicin for synergistic chemo-photodynamic therapy.

Phycocyanin (PC) is considered to be an effective natural photosensitizer, but it has not been well utilized as its inefficient biostability and intracellular accumulation. To overcome these limitations, the nano-sized PC particles (LAPC/DOX) were developed by grafting with lactobionic acid (LA) and loading with doxorubicin (DOX). Compared to the PC solution, the storage-stability and photostability of PC particles were remarkably increased, and the formation of nanoparticles further improved its biostability.

An effective NIR laser/tumor-microenvironment co-responsive cancer theranostic nanoplatform with multi-modal imaging and therapies.

Cancer is still a major threat to human health at present. Developing new types of integrated nanoplatforms for the accurate diagnosis and effective treatment of cancer is very significant. Herein, an intelligent dual-stage core-shell cancer theranostic nanoplatform (Fe3+@Au1Ag24@PbP) with NIR laser/tumor-microenvironment (TME) co-responsiveness and multi-modal imaging-therapy was successfully prepared, which was composed of the precisely structured oil-soluble Au1Ag24 nanoclusters (NCs) and Fe3+ ions easily assembled within the oil and aqueous phases of the polyethylene glycol (PEG) block grafted polyketal (PK) copolymer (PK-b-PEG, PbP) vesicles, respectively.

A sequentially responsive nanogel via Pt(IV) crosslinking for overcoming GSH-mediated platinum resistance.

Chemotherapy efficiency of platinum(II) (Pt(II)) is often attenuated owing to the low intracellular drugs concentration and glutathione (GSH)-mediated detoxification. To address these problems, we fabricated a step-by-step responsive nanogel (~160 nm) by copolymerization between four functional monomers. Hydrophilic methoxypolyethylene glycols (mPEG) distributedrandomly on the surface of particles endowed the nanogel with "stealth" property in blood circulation, while the chemical crosslinking inside particles by platinum(IV) (Pt(IV)) linker remarkably increased the stability of nanogel in vivo.

Dynamic precise dual-drug-backboned nano-prodrugs for selective chemotherapy.

To achieve an ideal drug delivery platform with precise composition and high tumor selectivity, the PEGylated dual-drug backboned prodrug was synthesized via the copolymerization between diamine monomer of ortho ester and cisplatin- demethylcantharidin conjugate (Pt(IV)-1), and then terminated by mPEG550-active ester. The amphipathic prodrug could self-assemble into nano-prodrugs, which endowed the precise structure and high drug loading. Moreover, the nano-prodrugs exhibited physicochemical stability at physiological pH (7.

Hybrid nanoparticles based on ortho ester-modified pluronic L61 and chitosan for efficient doxorubicin delivery.

Tumor intrinsic or acquired multidrug resistance (MDR) is still one of the major obstacles to the success of nanomedicine. To address this, the pH-sensitive nanoparticles (L61-OE-CS) with MDR-reversal ability were prepared by the crosslinking between acid-labile ortho-ester-modified pluronic (L61-OE) and chitosan (CS) for efficient doxorubicin (DOX) delivery. The size and micromorphology of the prepared nanoparticles were observed by dynamic light scanning and scanning electron microscopy and the nanoparticles displayed a uniform spherical shape with a diameter around 200 nm.

A small molecule nanodrug consisting of pH-sensitive ortho ester-dasatinib conjugate for cancer therapy.

The main objective of this paper is to develop a self-delivered prodrug system with nanoscale characteristics to enhance the efficacy of tumor therapy. The pH-sensitive prodrug was composed of ortho ester-linked dasatinib (DAS-OE), which was further self-assembled with or without doxorubicin (DOX) to obtain two carrier-free nanoparticles (DOX/DAS-OE NPs or DAS-OE NPs). The prodrug-based nanoparticles united the superiorities of small molecules and nano-assemblies together and displayed well-defined structure, uniform spherical shape, high drug loading ratio and on-demand drug release behavior.

Dynamic methotrexate nano-prodrugs with detachable PEGylation for highly selective synergistic chemotherapy.

To promote the highly selective synergistic chemotherapy, the pH-ultra-sensitive dynamic methotrexate nano-prodrugs with detachable PEGylation were successfully prepared via facile method, and the synergistic nanodrugs could be further constructed through encapsulating Doxorubicin (DOX) following the self-assembly process. The nano-prodrugs exhibited the low critical micelle concentration (CMC), negative zeta potential and stability for 5 days in PBS and FBS at physiological pH (7.4) for stable blood circulation, DePEGylation and dynamic size change at tumoral extracellular pH (6.

Self-assembled 5-fluorouracil-cinnamaldehyde nanodrugs for greatly improved chemotherapy in vivo.

The preferred cancer treatment is to achieve a high therapeutic effect as well as reduce side effects. In this study, we developed carrier-free nano drugs based on 5-fluorouracil (5FU) and cinnamaldehyde (CA) to meet the above goals. Two model drugs were spliced by acetal linkage and ester bond, which could self-assemble into nano drug particles (5FU-CA NPs) with a size of ∼170 nm.

Dynamic micelles with detachable PEGylation at tumoral extracellular pH for enhanced chemotherapy.

Although surface PEGylation of nanomedicines can decrease serum protein adsorption , it also blocks uptake by tumor cells. This dilemma could be overcome by employing detachably PEGylated strategy at tumoral extracellular microenvironment to achieve improved cellular uptake while prolonged circulation times. Herein, the amphiphilic graft copolymers with pH-sensitive ortho ester-linked mPEG in side chains and polyurethanes in backbone, can self-assemble into the free and doxorubicin (DOX)-loaded micelles.

Chemosensitizing micelles self-assembled from amphiphilic TPGS-indomethacin twin drug for significantly synergetic multidrug resistance reversal.

Vitamin E d-ɑ-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS) and indomethacin (IDM) can reverse multidrug resistance (MDR) via inhibiting P-glycoprotein (P-gp) and multidrug resistance associated protein 1 (MRP1) respectively, but their drawbacks in physicochemical properties limit their clinical application. To overcome these defects and enhance MDR reversal, the amphiphilic TPGS-IDM twin drug was successfully synthesized via esterification, and could self-assemble into free and paclitaxel-loaded (PTX-loaded) micelles. The micelles exhibited lower CMC values (5.