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Systemic metastasis-targeted nanotherapeutic reinforces tumor surgical resection and chemotherapy.

ABSTRACT: Failure of conventional clinical therapies such as tumor resection and chemotherapy are mainly due to the ineffective control of tumor metastasis. Metastasis consists of three steps: (i) tumor cells extravasate from the primary sites into the circulation system via epithelial-mesenchymal transition (EMT), (ii) the circulating tumor cells (CTCs) form "micro-thrombi" with platelets to evade the immune surveillance in circulation, and (iii) the CTCs colonize in the pre-metastatic niche. Here, we design a systemic metastasis-targeted nanotherapeutic (H@CaPP) composed of an anti-inflammatory agent, piceatannol, and an anti-thrombotic agent, low molecular weight heparin, to hinder the multiple steps of tumor metastasis. H@CaPP is found efficiently impeded EMT, inhibited the formation of "micro-thrombi", and prevented the development of pre-metastatic niche. When combined with surgical resection or chemotherapy, H@CaPP efficiently inhibits tumor metastasis and prolonged overall survival of tumor-bearing mice. Collectively, we provide a simple and effective systemic metastasis-targeted nanotherapeutic for combating tumor metastasis.

SUBMITTER: Xu M

PROVIDER: S-EPMC8160269 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Systemic metastasis-targeted nanotherapeutic reinforces tumor surgical resection and chemotherapy.

Xu Minjun M Hu Kaili K Liu Yipu Y Huang Yukun Y Liu Shanshan S Chen Yu Y Wang Dayuan D Zhou Songlei S Zhang Qian Q Mei Ni N Lu Huiping H Li Fengan F Gao Xiaoling X Chen Jun J

Nature communications 20210527 1

Failure of conventional clinical therapies such as tumor resection and chemotherapy are mainly due to the ineffective control of tumor metastasis. Metastasis consists of three steps: (i) tumor cells extravasate from the primary sites into the circulation system via epithelial-mesenchymal transition (EMT), (ii) the circulating tumor cells (CTCs) form "micro-thrombi" with platelets to evade the immune surveillance in circulation, and (iii) the CTCs colonize in the pre-metastatic niche. Here, we de ...[more]

PMID: 34045459

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Project description:ObjectiveThe change of bacterial flora structure in colorectal cancer (CRC) patients after treatment is not clear. The aim of this study was to explore the change and function of intestinal microflora in CRC before and after treatment.MethodThe 16S conserved region V3+V4 of intestinal flora obtained from CRC patients was sequenced and analyzed. Alpha and beta diversity indices were used to analyze the abundance and structure of gut flora. FAPROTAX, BugBase, and Tax4Fun software were used to analyze the species phenotypes and Kyoto Encyclopedia of Genes and Genomes Ontology (KO) function pathways.ResultsTotal abundance and structure of species in CRC patients were significantly increased compared with healthy people (control group) (P < 0.05), but there was no significant difference between CRC patients before and after treatment (P > 0.05). There was significant difference in relative abundance of bacteria at different levels (phylum, class, order, family, genus, and species) between the CRC group with after operation (CRC_O group) and chemotherapy (CRC_C group) treatment, particularly Prevotellaceae_UCG-001, Akkermansia, Fusicatenibacter, Tyzzerella_4, Megamonas, etc. in genus level. The KO function analysis showed that most of the bacteria with differences were mainly involved in the biosynthesis of lipopolysaccharide (Megamonas, Megasphaera, and Ruminococcus torques_group), protein digestion and absorption, renin-angiotensin system pathway (Akkermansia, Eubacterium_ruminantium_group, and Eubacterium_nodatum_group genus), adipocytokine signaling pathway and peroxisome pathway (Tyzzerella_4, Phascolarctobacterium, Ruminococcus_gnavus_group), and so on.ConclusionThe abundance of intestinal microflora in CRC patients was increased significantly contrasted to healthy people, and surgery and chemotherapy were hard to reduce this phenomenon. Megamonas was involved in lipopolysaccharide biosynthesis and carcinogenesis in colorectal cancer. Surgery and drug treatment did not reduced lipopolysaccharide biosynthesis but increased the number of probiotic Akkermansia population and reduced the pathogenic bacteria Tyzzerella_4, participate in adipocytokine signaling pathway, and affect metabolism.

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Systemic metastasis-targeted nanotherapeutic reinforces tumor surgical resection and chemotherapy.

Publications

Systemic metastasis-targeted nanotherapeutic reinforces tumor surgical resection and chemotherapy.

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