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Article ; Online: Macrophage membrane-biomimetic adhesive polycaprolactone nanocamptothecin for improving cancer-targeting efficiency and impairing metastasis

Kangkang Ying / Yifeng Zhu / Jianqin Wan / Chenyue Zhan / Yuchen Wang / Binbin Xie / Peirong Xu / Hongming Pan / Hangxiang Wang

Bioactive Materials, Vol 20, Iss , Pp 449-

2023 Volume 462

Abstract: The recent remarkable success and safety of mRNA lipid nanoparticle technology for producing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines has stimulated intensive efforts to expand nanoparticle strategies to treat various ... ...

Abstract	The recent remarkable success and safety of mRNA lipid nanoparticle technology for producing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines has stimulated intensive efforts to expand nanoparticle strategies to treat various diseases. Numerous synthetic nanoparticles have been developed for pharmaceutical delivery and cancer treatment. However, only a limited number of nanotherapies have enter clinical trials or are clinically approved. Systemically administered nanotherapies are likely to be sequestered by host mononuclear phagocyte system (MPS), resulting in suboptimal pharmacokinetics and insufficient drug concentrations in tumors. Bioinspired drug-delivery formulations have emerged as an alternative approach to evade the MPS and show potential to improve drug therapeutic efficacy. Here we developed a biodegradable polymer-conjugated camptothecin prodrug encapsulated in the plasma membrane of lipopolysaccharide-stimulated macrophages. Polymer conjugation revived the parent camptothecin agent (e.g., 7-ethyl-10-hydroxy-camptothecin), enabling lipid nanoparticle encapsulation. Furthermore, macrophage membrane cloaking transformed the nonadhesive lipid nanoparticles into bioadhesive nanocamptothecin, increasing the cellular uptake and tumor-tropic effects of this biomimetic therapy. When tested in a preclinical murine model of breast cancer, macrophage-camouflaged nanocamptothecin exhibited a higher level of tumor accumulation than uncoated nanoparticles. Furthermore, intravenous administration of the therapy effectively suppressed tumor growth and the metastatic burden without causing systematic toxicity. Our study describes a combinatorial strategy that uses polymeric prodrug design and cell membrane cloaking to achieve therapeutics with high efficacy and low toxicity. This approach might also be generally applicable to formulate other therapeutic candidates that are not compatible or miscible with biomimetic delivery carriers.
Keywords	Polymer prodrug ; Macrophage membrane ; Cancer nanomedicine ; Antimetastasis ; Nanocamptothecin ; Materials of engineering and construction. Mechanics of materials ; TA401-492 ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2023-02-01T00:00:00Z
Publisher	KeAi Communications Co., Ltd.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Hypermethylated

Wang, Lei / Dong, Lanlan / Xu, Jun / Guo, Lin / Wang, Yiran / Wan, Kangkang / Jing, Wei / Zhao, Lanbo / Feng, Xue / Zhang, Kailu / Guo, Miao / Zou, Yuliang / Zhang, Lianglu / Li, Qiling

Frontiers in oncology

2022 Volume 12, Page(s) 714663

Abstract: We aimed to estimate the diagnostic value of DNA methylation levels in cytological samples of endometrial cancer (EC) and atypical hyperplasia (AH). Two hypermethylated genes, namely, cysteine dioxygenase type 1 ( ...

Abstract	We aimed to estimate the diagnostic value of DNA methylation levels in cytological samples of endometrial cancer (EC) and atypical hyperplasia (AH). Two hypermethylated genes, namely, cysteine dioxygenase type 1 (
Language	English
Publishing date	2022-04-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2022.714663
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Article ; Online: Identification of two methylated fragments of an SDC2 CpG island using a sliding window technique for early detection of colorectal cancer

Ruibin Li / Bing Qu / Kangkang Wan / Changming Lu / Tingting Li / Fuxiang Zhou / Jun Lin

FEBS Open Bio, Vol 11, Iss 7, Pp 1941-

2021 Volume 1952

Abstract: Colorectal cancer (CRC) is one of the most common cancer types globally with a 5‐year survival rate of < 50% in China. Aberrant DNA methylation is one of the hallmarks of tumor initiation, progression, and metastasis. Here, we investigated the clinical ... ...

Abstract	Colorectal cancer (CRC) is one of the most common cancer types globally with a 5‐year survival rate of < 50% in China. Aberrant DNA methylation is one of the hallmarks of tumor initiation, progression, and metastasis. Here, we investigated the clinical performance of two differentially methylated regions (DMRs) in SDC2 CpG islands for the detection of CRC. A sliding window technique was used to identify the DMRs, and methylation‐specific PCR assay was used to assess the DMRs in 198 CRC samples and 54 normal controls. Two DMRs (DMR2 and DMR5) were identified using The Cancer Genome Atlas (TCGA) data, and the hypermethylation of DMR2 and DMR5 was detected in 90.91% (180/198) and 89.90% (178/198) of CRC samples, respectively. When combining DMR2 and DMR5, the sensitivity for CRC detection was 94.4% higher than that of DMR2 or DMR5 alone. Based on the above results, we propose using DMR2 and DMR5 as a sensitive biomarker to detect CRC.
Keywords	biomarkers ; colorectal cancer ; early detection ; methylation ; SDC2 ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Identification of two methylated fragments of an SDC2 CpG island using a sliding window technique for early detection of colorectal cancer.

Li, Ruibin / Qu, Bing / Wan, Kangkang / Lu, Changming / Li, Tingting / Zhou, Fuxiang / Lin, Jun

FEBS open bio

2021 Volume 11, Issue 7, Page(s) 1941–1952

Abstract: Colorectal cancer (CRC) is one of the most common cancer types globally with a 5-year survival rate of < 50% in China. Aberrant DNA methylation is one of the hallmarks of tumor initiation, progression, and metastasis. Here, we investigated the clinical ... ...

Abstract	Colorectal cancer (CRC) is one of the most common cancer types globally with a 5-year survival rate of < 50% in China. Aberrant DNA methylation is one of the hallmarks of tumor initiation, progression, and metastasis. Here, we investigated the clinical performance of two differentially methylated regions (DMRs) in SDC2 CpG islands for the detection of CRC. A sliding window technique was used to identify the DMRs, and methylation-specific PCR assay was used to assess the DMRs in 198 CRC samples and 54 normal controls. Two DMRs (DMR2 and DMR5) were identified using The Cancer Genome Atlas (TCGA) data, and the hypermethylation of DMR2 and DMR5 was detected in 90.91% (180/198) and 89.90% (178/198) of CRC samples, respectively. When combining DMR2 and DMR5, the sensitivity for CRC detection was 94.4% higher than that of DMR2 or DMR5 alone. Based on the above results, we propose using DMR2 and DMR5 as a sensitive biomarker to detect CRC.
MeSH term(s)	Biomarkers, Tumor/genetics ; Colorectal Neoplasms/diagnosis ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/pathology ; CpG Islands/genetics ; DNA Methylation/genetics ; Early Detection of Cancer/methods ; Humans ; Syndecan-2/genetics
Chemical Substances	Biomarkers, Tumor ; SDC2 protein, human ; Syndecan-2 (149769-25-5)
Language	English
Publishing date	2021-06-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2651702-4
ISSN	2211-5463 ; 2211-5463
ISSN (online)	2211-5463
ISSN	2211-5463
DOI	10.1002/2211-5463.13180
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Article ; Online: Macrophage membrane-biomimetic adhesive polycaprolactone nanocamptothecin for improving cancer-targeting efficiency and impairing metastasis.

Ying, Kangkang / Zhu, Yifeng / Wan, Jianqin / Zhan, Chenyue / Wang, Yuchen / Xie, Binbin / Xu, Peirong / Pan, Hongming / Wang, Hangxiang

Bioactive materials

2022 Volume 20, Page(s) 449–462

Abstract	The recent remarkable success and safety of mRNA lipid nanoparticle technology for producing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines has stimulated intensive efforts to expand nanoparticle strategies to treat various diseases. Numerous synthetic nanoparticles have been developed for pharmaceutical delivery and cancer treatment. However, only a limited number of nanotherapies have enter clinical trials or are clinically approved. Systemically administered nanotherapies are likely to be sequestered by host mononuclear phagocyte system (MPS), resulting in suboptimal pharmacokinetics and insufficient drug concentrations in tumors. Bioinspired drug-delivery formulations have emerged as an alternative approach to evade the MPS and show potential to improve drug therapeutic efficacy. Here we developed a biodegradable polymer-conjugated camptothecin prodrug encapsulated in the plasma membrane of lipopolysaccharide-stimulated macrophages. Polymer conjugation revived the parent camptothecin agent (e.g., 7-ethyl-10-hydroxy-camptothecin), enabling lipid nanoparticle encapsulation. Furthermore, macrophage membrane cloaking transformed the nonadhesive lipid nanoparticles into bioadhesive nanocamptothecin, increasing the cellular uptake and tumor-tropic effects of this biomimetic therapy. When tested in a preclinical murine model of breast cancer, macrophage-camouflaged nanocamptothecin exhibited a higher level of tumor accumulation than uncoated nanoparticles. Furthermore, intravenous administration of the therapy effectively suppressed tumor growth and the metastatic burden without causing systematic toxicity. Our study describes a combinatorial strategy that uses polymeric prodrug design and cell membrane cloaking to achieve therapeutics with high efficacy and low toxicity. This approach might also be generally applicable to formulate other therapeutic candidates that are not compatible or miscible with biomimetic delivery carriers.
Language	English
Publishing date	2022-06-23
Publishing country	China
Document type	Journal Article
ISSN	2452-199X
ISSN (online)	2452-199X
DOI	10.1016/j.bioactmat.2022.06.013
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Article ; Online: Adverse impact of a high allelic burden FLT3-ITD mutation on allogeneic hematopoietic stem cell transplantation in patients with cytogenetically normal AML.

Wan, Li / Ding, Shuqi / Xu, Mimi / Lv, Kangkang / Du, Yuanyuan / Wu, Depei / Xu, Mingzhu / Liu, Yuejun

International journal of hematology

2022 Volume 116, Issue 5, Page(s) 731–743

Abstract: Risks associated with the FLT3-ITD mutation in patients receiving chemotherapy alone for cytogenetic normal acute myeloid leukemia (CN-AML) depend on the allelic ratio (AR) and concomitant NPM1 mutation. Nevertheless, their prognostic ability after ... ...

Abstract	Risks associated with the FLT3-ITD mutation in patients receiving chemotherapy alone for cytogenetic normal acute myeloid leukemia (CN-AML) depend on the allelic ratio (AR) and concomitant NPM1 mutation. Nevertheless, their prognostic ability after allogeneic hematopoietic cell transplantation (allo-HCT) remains undetermined. Moreover, previous studies have revealed that haploidentical transplantation improves outcomes of FLT3-ITD patients. To elucidate whether this alteration also impacts prognosis of myeloablative allo-HCT upon first remission, we retrospectively reviewed the prognostic ability of FLT3-ITD mutations in 205 CN-AML patients. Our analysis demonstrated that FLT3-ITD AR was closely related to pretransplant MRD and induction response. Multivariate analysis showed that high-AR FLT3-ITD, pretransplant MRD and induction response were independent risk factors for CN-AML. In addition, we presented evidence that the high-AR FLT3-ITD patient prognosis was not overcome by haploidentical transplantation, but was markedly improved by cGVHD. More importantly, among patients with negative pretransplant MRD, high-AR FLT3-ITD patients did not have increased relapse risk, compared to low-AR FLT3-ITD and wild-type FLT3 patients. Our findings will aid in accurate prognostic stratification of FLT3-ITD patients. We also recommend further targeted and coordinated approaches to sustain durable remission following induction chemotherapy and allo-HCT in this high-risk patient population.
MeSH term(s)	Humans ; Retrospective Studies ; Mutation ; Nucleophosmin ; Leukemia, Myeloid, Acute/genetics ; Leukemia, Myeloid, Acute/therapy ; Hematopoietic Stem Cell Transplantation ; fms-Like Tyrosine Kinase 3/genetics
Chemical Substances	Nucleophosmin (117896-08-9) ; FLT3 protein, human (EC 2.7.10.1) ; fms-Like Tyrosine Kinase 3 (EC 2.7.10.1)
Language	English
Publishing date	2022-07-20
Publishing country	Japan
Document type	Journal Article
ZDB-ID	1076875-0
ISSN	1865-3774 ; 0917-1258 ; 0925-5710
ISSN (online)	1865-3774
ISSN	0917-1258 ; 0925-5710
DOI	10.1007/s12185-022-03423-8
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Article: Methylation of

Zhang, Lianglu / Dong, Lanlan / Lu, Changming / Huang, Wenxian / Yang, Cuiping / Wang, Qian / Lei, Ruixue / Sun, Rui / Wan, Kangkang / Li, Tingting / Sun, Fan / Gan, Tian / Lin, Jun / Yin, Lei

Frontiers in molecular biosciences

2021 Volume 8, Page(s) 706754

Abstract: Background: ...

Abstract	Background:
Language	English
Publishing date	2021-12-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2814330-9
ISSN	2296-889X
ISSN	2296-889X
DOI	10.3389/fmolb.2021.706754
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Article ; Online: Genome-wide methylation profiling identified methylated KCNA3 and OTOP2 as promising diagnostic markers for esophageal squamous cell carcinoma.

Bian, Yan / Gao, Ye / Lu, Chaojing / Tian, Bo / Xin, Lei / Lin, Han / Zhang, Yanhui / Zhang, Xun / Zhou, Siwei / Wan, Kangkang / Zhou, Jun / Li, Zhaoshen / Chen, Hezhong / Wang, Luowei

Chinese medical journal

2023

Abstract: Background: Early detection of esophageal squamous cell carcinoma (ESCC) can considerably improve the prognosis of patients. Aberrant cell-free DNA (cfDNA) methylation signatures are a promising tool for detecting ESCC. However, available markers based ... ...

Abstract	Background: Early detection of esophageal squamous cell carcinoma (ESCC) can considerably improve the prognosis of patients. Aberrant cell-free DNA (cfDNA) methylation signatures are a promising tool for detecting ESCC. However, available markers based on cell-free DNA methylation are still inadequate. This study aimed to identify ESCC-specific cfDNA methylation markers and evaluate the diagnostic performance in the early detection of ESCC. Methods: We performed whole-genome bisulfite sequencing (WGBS) for 24 ESCC tissues and their normal adjacent tissues. Based on the WGBS data, we identified 21,469,837 eligible CpG sites (CpGs). By integrating several methylation datasets, we identified several promising ESCC-specific cell-free DNA methylation markers. Finally, we developed a dual-marker panel based on methylated KCNA3 and OTOP2, and then, we evaluated its performance in our training and validation cohorts. Results: The ESCC diagnostic model constructed based on KCNA3 and OTOP2 had an AUC of 0.91 [95% CI: 0.85-0.95], and an optimal sensitivity and specificity of 84.91% and 94.32%, respectively, in the training cohort. In the independent validation cohort, the AUC was 0.88 [95% CI: 0.83-0.92], along with an optimal sensitivity of 81.5% and specificity of 92.9%. The model sensitivity for stage I-II ESCC was 78.4%, which was slightly lower than the sensitivity of the model (85.7%) for stage III-IV ESCC. Conclusions: The dual-target panel based on cfDNA showed excellent performance for detecting ESCC and might be an alternative strategy for screening ESCC.
Language	English
Publishing date	2023-08-31
Publishing country	China
Document type	Journal Article
ZDB-ID	127089-8
ISSN	2542-5641 ; 0366-6999 ; 1002-0187
ISSN (online)	2542-5641
ISSN	0366-6999 ; 1002-0187
DOI	10.1097/CM9.0000000000002832
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Article ; Online: The methylation of SDC2 and TFPI2 defined three methylator phenotypes of colorectal cancer.

Lei, Ruixue / Zhao, Yanteng / Huang, Kai / Wang, Qian / Wan, Kangkang / Li, Tingting / Yang, Haijun / Lv, Xianping

BMC gastroenterology

2022 Volume 22, Issue 1, Page(s) 88

Abstract: Background: Methylated SDC2 and TFPI2 are widely used for colorectal cancer (CRC) detection. However, they often miss some CRCs, which directly diminishes the sensitivity. Further investigations of the underlying mechanisms leading to the missed samples ...

Abstract	Background: Methylated SDC2 and TFPI2 are widely used for colorectal cancer (CRC) detection. However, they often miss some CRCs, which directly diminishes the sensitivity. Further investigations of the underlying mechanisms leading to the missed samples will facilitate developing more eligible methylation markers. Methods: CRC samples from TCGA and GEO datasets were divided into three groups, High-methylation/ High-methylation (HH), High-methylation/Low-methylation (HL), and Low-methylation/Low-methylation (LL) according to the methylation status of SDC2 and TFPI2 promoters. Variations in age, tumor location and microsatellite instable were then assessed between the three groups and verified in our custom cohort. Results: Samples of HL group preferred to derive from left-sided CRCs (P < 0.05). HH samples showed the highest microsatellite instability and mutation load (mean nonsynonymous mutations for HH/HL/LL: 10.55/3.91/7.02, P = 0.0055). Almost all mutations of BRAF, one of the five typical CpG island methylator phenotype (CIMP) related genes, were observed in HH group (HH/HL/LL: 51/0/1, P = 0.018). Besides, older patients were frequently found in HH group. Expression analysis identified 37, 84, and 22 group-specific differentially expressed genes (DEGs) for HH, HL, and LL, respectively. Functional enrichment analysis revealed that HH-specific DEGs were mainly related to transcription regulation, while LL-specific DEGs were enriched in the biological processes of extracellular matrix interaction and cell migration. Conclusions: The current study revealed that the performance of methylation-based markers might be affected by tumor location, patient age, mutation load and MSI, and these respective sides should be considered when developing new methylation markers for CRC detection.
MeSH term(s)	Colorectal Neoplasms/genetics ; Colorectal Neoplasms/pathology ; CpG Islands/genetics ; DNA Methylation ; Glycoproteins/genetics ; Humans ; Microsatellite Instability ; Mutation ; Phenotype ; Proto-Oncogene Proteins B-raf/genetics ; Syndecan-2/genetics
Chemical Substances	Glycoproteins ; SDC2 protein, human ; tissue-factor-pathway inhibitor 2 ; Syndecan-2 (149769-25-5) ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1)
Language	English
Publishing date	2022-02-28
Publishing country	England
Document type	Journal Article
ZDB-ID	2041351-8
ISSN	1471-230X ; 1471-230X
ISSN (online)	1471-230X
ISSN	1471-230X
DOI	10.1186/s12876-022-02175-3
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Article ; Online: Mechanism of LolCDE as a molecular extruder of bacterial triacylated lipoproteins

Stuti Sharma / Ruoyu Zhou / Li Wan / Shan Feng / KangKang Song / Chen Xu / Yanyan Li / Maofu Liao

Nature Communications, Vol 12, Iss 1, Pp 1-

2021 Volume 11

Abstract: In Gram-negative bacteria, lipoproteins are transported from the inner membrane (IM) to the outer membrane (OM) by the ATP-binding cassette (ABC) transporter LolCDE. Here the authors present cryo-EM structures of nanodisc-embedded LolCDE in different ... ...

Abstract	In Gram-negative bacteria, lipoproteins are transported from the inner membrane (IM) to the outer membrane (OM) by the ATP-binding cassette (ABC) transporter LolCDE. Here the authors present cryo-EM structures of nanodisc-embedded LolCDE in different states, providing mechanistic insight into the transport mechanism.
Keywords	Science ; Q
Language	English
Publishing date	2021-08-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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