Epigenetic tumor heterogeneity in the era of single-cell profiling with nanopore sequencing.

Nanopore sequencing has brought the technology to the next generation in the science of sequencing. This is achieved through research advancing on: pore efficiency, creating mechanisms to control DNA translocation, enhancing signal-to-noise ratio, and expanding to long-read ranges. Heterogeneity regarding epigenetics would be broad as mutations in the epigenome are sensitive to cause new challenges in cancer research. Epigenetic enzymes which catalyze DNA methylation and histone modification are dysregulated in cancer cells and cause numerous heterogeneous clones to evolve. Detection of this heterogeneity in these clones plays an indispensable role in the treatment of various cancer types. With single-cell profiling, the nanopore sequencing technology could provide a simple sequence at long reads and is expected to be used soon at the bedside or doctor's office. Here, we review the advancements of nanopore sequencing and its use in the detection of epigenetic heterogeneity in cancer.

PAMAM Dendritic Nanoparticle-Incorporated Hydrogel to Enhance the Immunogenic Cell Death and Immune Response of Immunochemotherapy.

The efficiency of chemotherapy is frequently affected by its multidrug resistance, immune suppression, and severe side effects. Its combination with immunotherapy to reverse immune suppression and enhance immunogenic cell death (ICD) has emerged as a new strategy to overcome the aforementioned issues. Herein, we construct a pH-responsive PAMAM dendritic nanocarrier-incorporated hydrogel for the co-delivery of immunochemotherapeutic drugs. The stepwise conjugation of moieties and drug load was confirmed by various techniques. In vitro experimental results demonstrated that PAMAM dendritic nanoparticles loaded with a combination of drugs exhibited spherical nanosized particles, facilitated the sustained release of drugs, enhanced cellular uptake, mitigated cell viability, and induced apoptosis. The incorporation of PAB-DOX/IND nanoparticles into thermosensitive hydrogels also revealed the formation of a gel state at a physiological temperature and further a robust sustained release of drugs at the tumor microenvironment. Local injection of this formulation into HeLa cell-grafted mice significantly suppressed tumor growth, induced immunogenic cell death-associated cytokines, reduced cancer cell proliferation, and triggered a CD8+ T-cell-mediated immune response without obvious systemic toxicity, which indicates a synergistic ICD effect and reverse of immunosuppression. Hence, the localized delivery of immunochemotherapeutic drugs by a PAMAM dendritic nanoparticle-incorporated hydrogel could provide a promising strategy to enhance antitumor activity in cancer therapy.