A facile combined therapy of chemotherapeutic agent and microRNA for hepatocellular carcinoma using non-cationic nanogel.

High drug resistance remains a challenge for chemotherapy against hepatocellular carcinoma (HCC). Combining chemotherapeutic agents with microRNA (miRNA), which simultaneously regulates multiple pathways, offers a promising approach to improve therapeutic efficacy against HCC. Although cationic amphiphilic copolymers have been used to co-deliver these agents, their effectiveness is often limited by low co-encapsulation efficiency and inherent cationic toxicity.

Tumor microenvironment activation amplify oxidative stress promoting tumor energy remodeling for mild photothermal therapy and cuproptosis.

Tumor metabolic reprogramming requires high levels of adenosine triphosphate (ATP) to maintain treatment resistance, which poses major challenges to chemotherapy and photothermal therapy. Especially, high levels of ATP promote copper ion efflux for limiting the curative effect of cuproptosis. Here, an HS-responsive mesoporous CuCl(OH)-loading chemotherapeutic cisplatin (CDDP) was synthesized, and the final nanoparticle, CDDP@CuCl(OH)-CDs (CDCuCDs), was encapsulated by electrostatic action with carbon dots (CDs).

Non-viral CRISPR activation system targeting VEGF-A and TGF-β1 for enhanced osteogenesis of pre-osteoblasts implanted with dual-crosslinked hydrogel.

Healing of large calvarial bone defects remains challenge but may be improved by stimulating bone regeneration of implanted cells. The aim of this study is to specially co-activate transforming growth factor β1 (TGF-β1) and vascular endothelial growth factor (VEGF-A) genes expressions in pre-osteoblast MC3T3-E1 cells through the non-viral CRISPR activation (CRISPRa) system to promote osteogenesis. A cationic copolymer carrying nucleus localizing peptides and proton sponge groups dimethyl-histidine was synthesized to deliver CRISPRa system into MC3T3-E1 cells with high cellular uptake, lysosomal escape, and nuclear translocation, which activated VEGF-A and TGF-β1 genes expressions and thereby additively or synergistically induced several osteogenic genes expressions.

A component-optimized chemo-dynamic nanoagent for enhanced tumour cell-selective chemo-dynamic therapy with minimal side effects in a glioma mouse model.

Although CuO-deposited bovine serum albumin (CuO-BSA) and glucose oxidase (GOx) were combined to achieve HO self-supplied chemo-dynamic therapy (CDT) and glucose consumption-based starvation therapy, the uses of copper and GOx have not been optimized to enhance tumour-selective reactive oxygen species (ROS) generation and minimize toxicity to normal cells as well. Here, chemo-dynamic nanoparticles (CBGP NPs) were prepared through a facile biomineralization process and subsequent coatings with GOx and the cationic polymer PEG-PEI. Through optimizing the use of copper, GOx, and PEG-PEI, the CBGP NPs showed high cellular uptake efficiency, enhanced tumour-selective ROS generation, and minimal side effects toward normal cells.