A ROS-responsive and scavenging hydrogel for postoperative abdominal adhesion prevention.

Postoperative abdominal adhesion (PAA) widely occurs after abdominal surgery, which often produces severe complications. However, there were still no satisfactory anti-adhesive products including barriers and anti-adhesive agents. Herein, we developed a ROS-responsive and scavenging hydrogel barrier, termed AHBC/PSC, wherein the monomer AHBC was synthesized by phenylboronic acid (PBA)-modified hyaluronic acid (HA-PBA) further grafted with adipic dihydrazide (ADH) and PBA-based chlorogenic acid (CGA) via ROS-sensitive borate ester bond, and the other monomer PSC was constructed by polyvinyl alcohol (PVA) grafted with sulfated betaine (SB) and p-hydroxybenzaldehyde (CHO).

ROS-responsive sprayable hydrogel as ROS scavenger and GATA6 macrophages trap for the prevention of postoperative abdominal adhesions.

Postoperative abdominal adhesions are a common clinical problem after surgery and can cause many serious complications. Current most commonly used antiadhesion products are less effective due to their short residence time and focus primary on barrier function. Herein, we developed a sprayable hydrogel barrier (sHA-ADH/OHA-E) with self-regulated drug release based on ROS levels at the trauma site, to serve as a smart inflammatory microenvironment modulator and GATA6 macrophages trap for non-adherent recovery from abdominal surgery.

Bortezomib prodrug catalytic nanoreactor for chemo/chemodynamic therapy and macrophage re-education.

Chemodynamic therapy (CDT), an emerging tumor-specific therapeutic modality, is frequently restrained by insufficient intratumoral Fenton catalysts and increasingly inefficient catalysis caused by the continuous consumption of limited HO within tumors. Herein, we engineered a pH-responsive bortezomib (BTZ) polymer prodrug catalytic nanoreactor (HeZn@HA-BTZ) capable of self-supplying Fenton catalyst and HO. It is aimed for tumor-specific chemo/chemodynamic therapy via oxidative stress and endoplasmic reticulum (ER) stress dual-amplification and macrophage repolarization.

A DNA damage nanoamplifier for the chemotherapy of triple-negative breast cancer via DNA damage induction and repair blocking.

Due to a powerful DNA damage repair system and a lack of surface markers, there is currently no effective chemotherapy or tailored targeted therapies available for triple-negative breast cancer (TNBC) treatment. Herein, a tailored DNA damage nanoamplifier (Lipo@Nir/Pt(IV)) was engineered to simultaneously induce DNA damage and inhibit DNA reparation for highly efficient TNBC treatment. A newly synthesized Pt(IV) prodrug, the DNA damaging inducer, and the hydrophobic poly(ADP-ribose) polymerases (PARPs) inhibitor niraparib, which is used as the DNA repair blocker, were concurrently encapsulated in highly biocompatible PEGylated liposomes to prepare Lipo@Nir/Pt(IV), for enhanced cancer therapy and future clinical translation.

Tumor-targeted hyaluronic acid-based oxidative stress nanoamplifier with ROS generation and GSH depletion for antitumor therapy.

Tumor cells with innate oxidative stress are more susceptible to exogenous ROS-mediated oxidative damage than normal cells. However, the generated ROS could be scavenged by the overexpressed GSH in cancer cells, thus causing greatly restricted efficiency of ROS-mediated antitumor therapy. Herein, using cinnamaldehyde (CA) as a ROS generator while β-phenethyl isothiocyanate (PEITC) as a GSH scavenger, we designed a tumor-targeted oxidative stress nanoamplifier to elevate intracellular ROS level and synchronously suppress antioxidant systems, for thorough redox imbalance and effective tumor cells killing.

Glutathione-responsive copper-disulfiram nanoparticles for enhanced tumor chemotherapy.

Disulfiram (DSF), a familiar FDA-approved drug used for alcohol withdrawal, has recently been verified with potent antitumor therapeutic effect by generating Cu(DTC), which is the complex of its metabolite diethyldithiocarbamate (DTC) and copper. However, its poor tumor selectivity and insufficient endogenous Cu concentration within tumor site largely hinders the application of DSF-based antitumor therapy. Therefore, a GSH-responsive coordination nanoparticles (Cu-IXZ@DSF) was established as a copper carrier to achieve synchronous but separate delivery of Cu and DSF without antitumor ability, further to realize selectively triggered tumor in situ Cu(DTC) generation for antitumor therapy.

Engineered macrophages as near-infrared light activated drug vectors for chemo-photodynamic therapy of primary and bone metastatic breast cancer.

Patients with primary and bone metastatic breast cancer have significantly reduced survival and life quality. Due to the poor drug delivery efficiency of anti-metastasis therapy and the limited response rate of immunotherapy for breast cancer, effective treatment remains a formidable challenge. In this work, engineered macrophages (Oxa(IV)@ZnPc@M) carrying nanomedicine containing oxaliplatin prodrug and photosensitizer are designed as near-infrared (NIR) light-activated drug vectors, aiming to achieve enhanced chemo/photo/immunotherapy of primary and bone metastatic tumors.