Injectable hydrogels for personalized cancer immunotherapies.

The field of cancer immunotherapy has shown significant growth, and researchers are now focusing on effective strategies to enhance and prolong local immunomodulation. Injectable hydrogels (IHs) have emerged as versatile platforms for encapsulating and controlling the release of small molecules and cells, drawing significant attention for their potential to enhance antitumor immune responses while inhibiting metastasis and recurrence. IHs delivering natural killer (NK) cells, T cells, and antigen-presenting cells (APCs) offer a viable method for treating cancer. Indeed, it can bypass the extracellular matrix and gradually release small molecules or cells into the tumor microenvironment, thereby boosting immune responses against cancer cells. This review provides an overview of the recent advancements in cancer immunotherapy using IHs for delivering NK cells, T cells, APCs, chemoimmunotherapy, radio-immunotherapy, and photothermal-immunotherapy. First, we introduce IHs as a delivery matrix, then summarize their applications for the local delivery of small molecules and immune cells to elicit robust anticancer immune responses. Additionally, we discuss recent progress in IHs systems used for local combination therapy, including chemoimmunotherapy, radio-immunotherapy, photothermal-immunotherapy, photodynamic-immunotherapy, and gene-immunotherapy. By comprehensively examining the utilization of IHs in cancer immunotherapy, this review aims to highlight the potential of IHs as effective carriers for immunotherapy delivery, facilitating the development of innovative strategies for cancer treatment. In addition, we demonstrate that using hydrogel-based platforms for the targeted delivery of immune cells, such as NK cells, T cells, and dendritic cells (DCs), has remarkable potential in cancer therapy. These innovative approaches have yielded substantial reductions in tumor growth, showcasing the ability of hydrogels to enhance the efficacy of immune-based treatments. STATEMENT OF SIGNIFICANCE: As cancer immunotherapy continues to expand, the mode of therapeutic agent delivery becomes increasingly critical. This review spotlights the forward-looking progress of IHs, emphasizing their potential to revolutionize localized immunotherapy delivery. By efficiently encapsulating and controlling the release of essential immune components such as T cells, NK cells, APCs, and various therapeutic agents, IHs offer a pioneering pathway to amplify immune reactions, moderate metastasis, and reduce recurrence. Their adaptability further shines when considering their role in emerging combination therapies, including chemoimmunotherapy, radio-immunotherapy, and photothermal-immunotherapy. Understanding IHs' significance in cancer therapy is essential, suggesting a shift in cancer treatment dynamics and heralding a novel period of focused, enduring, and powerful therapeutic strategies.

In vitro expansion of human adipose-derived stem cells with delayed senescence through dual stage release of curcumin from mesoporous silica nanoparticles/electrospun nanofibers.

Electrospun nanofibers (NFs) were utilized to realize the dual-stage release of curcumin (Curc) to fully support the attachment, viability and proliferation of adipose-derived stem cells (hADSCs) with a delay in cellular senescence. For this purpose, both free Curc and Curc-loaded mesoporous silica nanoparticles (Curc@MSNs) were integrated into the electrospun polycaprolactone/gelatin (PCL/GEL) nanofibrous scaffolds and characterized via FTIR, BET, FE-SEM and TEM. In vitro drug release results demonstrated strong dual stage-discharge of Curc from the Curc/Curc@MSNs-NFs. Because of the combination of initial rapid release and late extended drug release, hADSCs cultured on the Curc/Curc@MSNs-NFs showed the greatest adhesion, metabolic activity and proliferation rate with a fibroblastic phenotype after 28 days of culture. Besides, a significant reduction in senescence-associated lysosomal α-L-fucosidase (SA-α-Fuc) expression and activity was also measured in hADSCs cultured on the Curc/Curc@MSNs-NFs. Moreover, not only the expression of hTERT in mRNA and protein levels was considerably increased in hADSCs seeded on the Curc/Curc@MSNs-NFs, but also the telomerase activity and telomere length were significantly enhanced in the scaffolds compared to the other types of scaffolds and control group. These results uncovered the potential of the two-stage discharge profile of Curc from Curc/Curc@MSNs-NFs to provide the biofunctionality of long-term cultured hADSCs for efficient stem cell-based regenerative therapies.

An Interleukin-6 Single Nucleotide Polymorphism and Susceptibility to Prostate Adenocarcinoma and Bone Metastasis in an Iranian Population

Objective: Interleukin-6 (IL-6) is an inflammatory cytokine shown to be a strong factor for growth, proliferation and metastasis with many malignancies. The promoter single nucleotide polymorphism (SNPs) -174G>C (rs1800795) can alter the transcriptional pattern of this gene. The present study was aimed at assessing effects of the IL-6 (rs1800795) SNP on risk of benign prostate hyperplasia (BPH) and prostatic adenocarcinoma (PCa). Methods: The project was performed on 112 men with PCa, 118 with BPH and 250 healthy controls. After DNA extraction, genotyping of IL-6 (rs1800795) was performed using PCR TaqMan Allelic Discrimination (ABI MGB). Results: The G allele frequency for rs1800795 of the IL-6 gene was 74.1%, 68.6% and 67% in PCa patients, BPH patients and healthy men, respectively. PCa and control groups showed significant differences (P =0.030, OR = 1.73, 95% CI: 1.05-2.21). The GG genotype was more frequent in the PCa group, whereas the GC genotype was more common in the BPH in comparison to other groups. Conclusion: The current study identified IL-6 -174G>C (rs1800795) as a significant predictor of susceptibility for prostate cancer and bone metastasis in a northwest Iranian population.