Multidrug resistance (MDR) is a key factor in chemotherapy failure and tumor recurrence. The inhibition of drug efflux and autophagy play important roles in MDR therapy. Herein, a multifunctional delivery system (HA-MIL-125@DVMA) was prepared for synergistically reverse tumor MDR. Tumor-targeted hollow MIL-125-Ti nanoparticles were used to load the doxorubicin–vitamin E succinate (DV) prodrug and 3-methyladenine (3-MA) to enhance reverse MDR effects. The pH-sensitive DV can kill tumor cells and inhibit P-gp-mediated drug efflux, and 3-MA can inhibit autophagy. HA-MIL-125@DVMA had uniformly distributed particle size and high drug-load content. The nanoparticles could effectively release the drugs into tumor microenvironment due to the rapid hydrazone bond-breaking under low pH conditions, resulting in a high cumulative release rate. In in vitro cellular experiments, the accumulation of HA-MIL-125@DVMA and HA-MIL-125@DV in MCF-7/ADR cells was significantly higher than that in the control groups. Moreover, the nanoparticles significantly inhibited drug efflux in the cells, ensuring the accumulation of the drugs in cell cytoplasm and causing drug-resistant cells’ death. Importantly, HA-MIL-125@DVMA effectively inhibited tumor growth without changes in body weight in tumor-bearing mice. In summary, the combination of the acid-sensitive prodrug DV and autophagy inhibitor 3-MA in a HA-MIL-125 nanocarrier can enhance the antitumor effect and reverse tumor MDR.

Chemotherapy (CT) plays an important role in the antitumor process, but the unsatisfactory therapeutic efficacy and the obvious toxic side effects of CT seriously restrict its application. To overcome the limitations of CT, the strategy of chemotherapy enhanced by chemodynamic therapy (CDT) and photothermal therapy (PTT) has been considered a promising approach to improve the anticancer effect. Herein, a novel GSH-activatable Cu²⁺-Quercetin network (QC) was synthesized via a convenient strategy to load Au nanoparticles (NPs) and DOX, named QCDA, for the synergistic therapy of CT/CDT/PTT. The results showed that QCDA exhibited GSH-sensitive degradation and “cargos” release in cancer cells, and then PTT and CDT caused by Au NPs and Cu⁺ significantly enhanced the CT effect of DOX and Quercetin on anticancer. More importantly, the PTT and depleted GSH accelerated the Fenton-like ionization process resulting in facilitating the CDT efficiency. Collectively, the multi-mode synergistic strategy of CT/CDT/PTT, which showed an excellent therapeutic effect, maybe a potential therapeutic pathway for anticancer.

Doxorubicin(DOX), which is a first-line broad-spectrum chemotherapeutic agent remains constrained clinical efficacy by dose-dependent cardiotoxicity, multidrug resistance, and systemic toxicity. Recent advancements in nanocarrier-based drug delivery systems have demonstrated remarkable potential to enhance tumor-specific accumulation, modulate drug release kinetics, and mitigate off-target effects through innovative engineering strategies. Contemporary nanocarrier researchers have expanded beyond conventional efforts to enhance tumor targeting and optimize drug release kinetics, which emphasizes the pathophysiological roles of the tumor microenvironment (TME) in mediating oncogenesis, neoplastic progression, and therapeutic resistance. This review emphasizes two pivotal strategies: (1) Structural innovation in tumor-targeting nanocarrier design through stimuli-responsive release mechanisms and molecular recognition targeting; (2) Therapeutic reprogramming of the TME via combinatorial extracellular matrix modulation. Through systematic analysis of 2019-2022 literatures from major scientific databases, this review synthesizes the advances in DOX-loaded nanocarriers targeting TME reprogramming and immunomodulation, and evaluates novel delivery platforms that overcome DOX's dose-limiting toxicity while potentiating antitumor efficacy.

Fungal infections have emerged as a global health challenge. The incidence of fungal infections increases after breast surgery or chemotherapy for tumors, which poses a serious threat to patients. ...

Ulcerative colitis (UC) is a chronic idiopathic inflammatory bowel disease primarily affecting the colon and rectum, characterized by complex pathogenesis and clinical challenges, such as disease recurrence and potential malignant transformation. The pan-JAK inhibitor tofacitinib (TOF) has emerged as an effective therapeutic option for inducing and maintaining clinical remission in moderate-to-severe UC. Recent advances in nanomedicine have identified milk-derived exosomes (mEXOs) as promising natural drug delivery vehicles due to their favorable physicochemical properties and biocompatibility. Therefore, an oral TOF-loaded mEXOs system (mEXOs@TOF) was successfully developed, which exhibited favorable pharmaceutical characteristics, including stability, uniform size distribution, high drug-loading capacity, and efficient macrophage uptake. The therapeutic efficacy of mEXOs@TOF was mediated through multifaceted mechanisms including suppression of pro-inflammatory cytokines (IL-6, IFN-γ, NO), elevation of anti-inflammatory IL-10 levels, reduction of reactive oxygen species production, and inhibition of JAK-STAT3 signaling pathway activation. Comprehensive in vitro and in vivo assessments of mEXOs@TOF confirmed the enhanced anti-inflammatory treatment on UC, with no detectable adverse effects. Collectively, the mEXOs@TOF nanodelivery system represents a targeted therapeutic strategy for improving UC treatment.