Dataset Information

Nano-drug System Based on Hierarchical Drug Release for Deep Localized/Systematic Cascade Tumor Therapy Stimulating Antitumor Immune Responses.

ABSTRACT: Inaccessibility of deep-seated malignant cells in the central region of tumors and uncontrollable tumor recurrence represent a significant challenge for conventional synergistic cancer therapy. Herein, we designed a novel nanoplatform based on hierarchical drug release for deep cascade cancer therapy including localized photothermal therapy, systematic chemotherapy, and elicited immune responses. Methods: The first-step chemotherapy could be carried out by polydopamine (PDA) releasing doxorubicin (DOX) in the specific microenvironment of lysosomes (pH 5.5). The branched gold nanoshells and PDA converted the light to heat efficiently to accomplish the second-step photothermal therapy and collapsed biomimetic vesicles (BVs) to release paclitaxel (PTX), which promoted the third-step of chemotherapy and triggered immune responses. Results: After 10 days of treatment, there were no obvious residual tumors in tumor-bearing mice. Significantly, 10 days after stopping treatment, mice in the drug immune-therapeutic group showed little tumor recurrence (1.5 times) compared to substantial recurrence (20 times) in the conventional treatment group. Conclusion: The hierarchical drug release and cascade therapeutic modality enhance the penetration of drugs deep into the tumor tissue and effectively inhibit recurrence. This cascade therapeutic modality provides a novel approach for more effective cancer therapy.

SUBMITTER: He Y

PROVIDER: S-EPMC6568183 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Nano-drug System Based on Hierarchical Drug Release for Deep Localized/Systematic Cascade Tumor Therapy Stimulating Antitumor Immune Responses.

He Yuchu Y Cong Cong C Li Xiaoling X Zhu Ruiyan R Li Anshuo A Zhao Shuxian S Li Xiaowei X Cheng Xin X Yang Mengxue M Gao Dawei D

Theranostics 20190504 10

Inaccessibility of deep-seated malignant cells in the central region of tumors and uncontrollable tumor recurrence represent a significant challenge for conventional synergistic cancer therapy. Herein, we designed a novel nanoplatform based on hierarchical drug release for deep cascade cancer therapy including localized photothermal therapy, systematic chemotherapy, and elicited immune responses. <b>Methods:</b> The first-step chemotherapy could be carried out by polydopamine (PDA) releasing dox ...[more]

PMID: 31244931

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Project description:To better understand the roles of WC-1, WC-2 and other putative photoreceptors in mediation of light signals and to identify new components in light sensing cascades, we used microarrays with genome-wide coverage to characterize light-inducible transcriptional changes in Neurospora crassa. After unsupervised hierarchical clustering of 90 microarrays, 316 genes, representing about 3.21% of the total genome, showed robust and consistent light responses. As expected, WC-1 and WC-2 knockout strains both exhibited severe impairments in response to a continuous white light stimulus, confirming their dominant roles in light sensing cascades. Knockout strains of 5 newly-identified light-inducible transcription factors were further characterized for their potential function in mediating light signals. Interestingly, one early light-inducible transcription factor, Submerged Protoperithecia-1 (SUB-1), appeared to be essential in mediating a large number of late light response, providing a direct molecular connection between early and late light responses. Furthermore, a novel motif, which is overrepresented among late light responsive genes, was demonstrated to be necessary for full induction of late light responses in vivo. Taken together, these results reveal a simple hierarchical light-sensing cascade in Neurospora, which is initially invoked by light-activated White Collar Complex (WCC) binding to Light Response Elements (LREs) of the primary target genes, including SUB-1. Subsequently, the induction of SUB-1 and other activators activate downstream targets. Thus, light responses of well-defined timing and amplitude can be orchestrated to meet the differential needs of underlying biological processes. Keywords: time course, light response Two-color microarray, totally 135 arrays were used to characterize light response in different photoreceptor knockout strains. Alexa Fluor 555 was consistently used to label cDNA synthesized from reference RNA, which is a mixture containing equal amounts of RNA samples harvested from different circadian time points and light treatment durations. The same batch of pooled RNA was used as a reference for each array experiment. Alexa Fluor 647 was used exclusively to label cDNA representing sample RNA.

Dataset Information

Nano-drug System Based on Hierarchical Drug Release for Deep Localized/Systematic Cascade Tumor Therapy Stimulating Antitumor Immune Responses.

Publications

Nano-drug System Based on Hierarchical Drug Release for Deep Localized/Systematic Cascade Tumor Therapy Stimulating Antitumor Immune Responses.

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