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Cancer stem cells (CSCs) are a major hindrance to clinical cancer treatment. Owing to their high tumorigenic and metastatic potential, CSCs are vital in malignant tumor initiation, growth, metastasis, and therapeutic resistance, leading to tumorigenesis and recurrence. Compared with normal tumor cells, CSCs express high levels of surface markers (CD44, CD90, CD133, etc.) and activate specific signaling pathways (Wnt/β-catenin, Notch, and Hedgehog). Although Current drug delivery systems (DDS) precisely target CSCs, the heterogeneity and multidrug resistance of CSCs impede CSC isolation and screening. Conversely, hydrogel DDSs exhibit good biocompatibility and high drug delivery efficiency. Hydrogels are three-dimensional (3D) spatial structures for drug encapsulation that facilitate the controlled release of bioactive molecules. Hence, hydrogels can be loaded with drugs to precisely target CSCs. Their 3D structure can also culture non-CSCs and facilitate their transformation into CSCs. for identification and isolation. Given that their elastic modulus and stiffness characteristics reflect those of the cellular microenvironment, hydrogels can simulate extracellular matrix pathways and markers to regulate CSCs, disrupting the equilibrium between CSC and non-CSC transformation. This article reviews the CSC microenvironment, metabolism, signaling pathway, and surface markers. Additionally, we summarize the existing CSC targeting strategies and explore the application of hydrogels for CSC screening and treatment. Finally, we discuss potential advances in CSC research that may lead to curative measures for tumors through targeted and precise attacks on CSCs.

Abstract Deep penetration and downregulation of heat shock protein (HSP) expression in multimodal synergistic therapy are promising approaches for curing cancer in clinical trials. However, free small‐molecule drugs and most drug vehicles have a low delivery efficiency deep into the tumor owing to poor drug penetration and hypoxic conditions at the tumor site. In this study, the objective is to use reactive oxygen species (ROS)‐responsive supramolecular gels co‐loaded with the photosensitizer Zn(II) phthalocyanine tetrasulfonic acid (ZnPCS4) and functionalized tetrahedral DNA (TGSAs) (G@P/TGSAs) to enhance deep tissue and cell penetration and block the HSP90 pathway for chemo‐ photodynamic therapy (PDT) ‐ photothermal therapy (PTT) trimodal synergistic therapy. The (G@P/TGSAs) are injected in situ into the tumor to release ZnPCS4 and TGSAs under high ROS concentrations originating from both the tumor and PDT. TGSAs penetrate deeply into tumor tissues and augment photothermal therapy by inhibiting the HSP90 pathway. Proteomics show that HSP‐related proteins and molecular chaperones are inhibited/activated, inhibiting the HSP90 pathway. Simultaneously, the TGSA‐regulated apoptotic pathway is activated. In vivo study demonstrates efficient tumor penetration and excellent trimodal synergistic therapy (45% tumor growth inhibition).

Chemotherapy for tumors occasionally results in drug resistance, which is the major reason for the treatment failure. Higher drug doses could improve the therapeutic effect, but higher toxicity limits the further treatment. For overcoming drug resistance, functional nano-drug delivery system (NDDS) has been explored to sensitize the anticancer drugs and decrease its side effects, which are applied in combating multidrug resistance (MDR) via a variety of mechanisms including bypassing drug efflux, controlling drug release, and disturbing metabolism. This review starts with a brief report on the major MDR causes. Furthermore, we searched the papers from NDDS and introduced the recent advances in sensitizing the chemotherapeutic drugs against MDR tumors. Finally, we concluded that the NDDS was based on several mechanisms, and we looked forward to the future in this field.

Chemotherapy (CT) can convert tumor cells into “tumor vaccines” through immunogenic cell death (ICD). However, the antitumor immunity elicited by CT-induced tumor vaccines is weak. Therefore, developing efficient CT-induced tumor vaccines is a challenge. Herein, we report a novel strategy to induce CT with a strong immunogenic effect. Targeted tetrahedral DNA nanostructures modified by AS1411 and immune adjuvant CpG (abbreviation: ACT) were used to achieve a multi-drug co-loading system of DOX and methylene blue (MB, photosensitizer for photodynamic therapy), ACT-loaded DOX and MB (ACT@DM), for multi-mode and combined chemo-photo-immune therapy. ACT@DM effectively generated reactive oxygen species and promoted cellular uptake through photochemical internalization, showing an excellent antitumor effect. Furthermore, ACT@DM induced a significant ICD effect under light irradiation, activated immune cells, and promoted the maturation of dendritic cells and secretion of related cytokines, thereby resulting in the activation and infiltration of T lymphocytes. The combination of CT-photo-immune therapy significantly enhanced the proportions of cytotoxic T cells (CD8+ CTL) and CD8+ CTL/regulatory T cells, indicating effective activation of T cells and improvement of immunosuppression, which cooperatively inhibited tumor growth. This study provides a simple but effective strategy for exploring antitumor immunotherapy, achieving high-efficiency T cell activation, and multimodal combination therapy.

IntroductionObesity-related ovulation abnormalities (OA) affect fertility. LSG is the most frequent bariatric operation. However, no research has identified a reliable indicator for predicting OA recovery after LSG. The purpose of this research was to examine the prognostic usefulness of preoperative the luteinizing hormone (LH) to follicle-stimulating hormone (FSH) ratio (LFR).MethodsOur department conducted a prospective study from 2016 to 2021. Venous blood was typically tested 3 days before surgery to get the preoperative LFR. Descriptive data, preoperative and postoperative variables were also collected. Binary logistic regression related preoperative LFR with OA recovery. The receiver operating characteristic (ROC) curve evulated preoperative LFR’s predictive capability.ResultsA total of 157 women with a complete follow-up of one year were included. LFR was the only factor linked with OA (P < 0.001). AUC (area under the ROC curve) = 0.915, cutoff = 1.782, sensitivity = 0.93, and specificity = 0.82.DiscussionOverall, LSG has a favorable surgical result, with a %TWL of 66.082 ± 12.012 at 12 months postoperatively. Preoperative sexual hormone levels, as expressed by LFR, has the potential to predict the fate of OA following LSG at one year post-operatively.