Pathology of myocardial infarction (MI) undergoes continuous spatiotemporal transformation, during which immediate elevated reactive oxygen species (ROS) and subsequent upregulated connective tissue growth factor (CTGF) exacerbate the impairment of cardiac functions. The major challenge lies in designing biomaterials that can adaptively respond to the temporal changes in the MI microenvironment. Herein, we prepared ROS-responsive dual drug-loaded core–shell microgels (SaB/Cand@C-S MGs) using microfluidic chip technology. The hydrogel shell was made from ROS-eliminating hyperbranched poly(acrylate-capped thioketone-containing ethylene glycol) (HBPAK) and methacrylated hyaluronic acid (HAMA), which was further encapsulated with hydrophilic salvianolic acid B (SaB). The oleogel core was loaded with hydrophobic candesartan (Cand). This structure enabled programmed drug release by utilizing ROS-responsive shell. The release of Cand from the SaB/Cand@C-S MGs in vitro was significantly accelerated in the presence of H 2 O 2 , reaching to 68% over 21 d, compared to 24% in PBS. In a rat MI model, minimally invasive injection of the SaB/Cand@C-S MGs into the infarcted area demonstrated both short-term anti-inflammatory effect and long-term benefit in fibrosis suppression. This phase-targeted approach ultimately resulted in improved cardiac functions, reduced fibrosis, and decreased ventricular dilation. The core–shell microgels as a drug reservoir offer a programmed drug delivery strategy adaptive to the specific phases of MI, showing great potential for applications.
Drug resistance renders standard chemotherapy ineffective in the treatment of connective tissue growth factor (CTGF)-overexpressing breast cancer. By co-embedding the breast tumor cell-penetrating peptide (PEGA-pVEC) and hyaluronic acid (HA) as a targeting media, novel cascaded targeting nanoparticles (HACT NPs) were created on a rattle mesoporous silica (rmSiO 2 ) scaffold for the pinpoint delivery of siRNAs along with an anticancer drug, aiming at overcoming the drug resistance of CTGF-overexpressing breast cancer in vivo . The targeting nanoparticles selectively accumulated in the vasculature under the guidance of the PEGA-pVEC peptide, cascaded by receptor-mediated endocytosis with the aid of another targeting agent, HA, presenting a greater in vivo tumor targeting ability than single targeting ligand vectors. In addition, an HA shell prevented the leakage of therapeutic drugs during the cargo transport process, until the hyaluronidase (HAase)-triggered degradation upon lysosomes entering, guaranteeing a controllable drug release inside the target cells. When the protective shell disintegrates, the released siRNA took charge to silence the gene associated with drug resistance, CTGF, thus facilitating doxorubicin-induced apoptosis. The cascaded targeting media (PEGA-pVEC and HA) advances precision-guided therapy in vivo , while the encapsulation of siRNAs into a chemotherapy drug delivery system provides an efficient strategy for the treatment of drug resistance cancers.
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