Regulating Twisted Skeleton to Construct Organ‐Specific Perylene for Intensive Cancer Chemotherapy

The systemic use of pharmaceutical drugs for cancer patients is a compromise between desirable therapy and side effects because of the intrinsic shortage of organ‐specific pharmaceutical drug. Design and construction of pharmaceutical drug to achieve the organ‐specific delivery is thus desperately d...

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Published inAngewandte Chemie International Edition Vol. 60; no. 29; pp. 16215 - 16223
Main Authors Liu, Zhonghua, Wang, Xuejuan, Chen, Qing, Ma, Feiyan, Huang, Yongwei, Gao, Yijian, Deng, Qingyuan, Qiao, Zeng‐Ying, Xing, Xiaoyi, Zhu, Jianling, Lu, Feng, Wang, Hao
Format Journal Article
LanguageEnglish
Published WEINHEIM Wiley 12.07.2021
Wiley Subscription Services, Inc
EditionInternational ed. in English
Subjects
Adenosine triphosphate
Animals
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Apoptosis
Apoptosis - drug effects
ATP
Autophagy
Calcium
Cell Line, Tumor
Cell Proliferation - drug effects
Chemistry
Chemistry, Multidisciplinary
Chemotherapy
Drug development
Drug Screening Assays, Antitumor
Endoplasmic reticulum
fluorescence image
Humans
Hydrogen peroxide
Lung cancer
Lung Neoplasms - drug therapy
Lung Neoplasms - metabolism
Lung Neoplasms - pathology
Metastases
Mice
Mitochondria
molecular mechanism
perylene
Perylene - analogs & derivatives
Perylene - chemistry
Perylene - pharmacology
Phagocytosis
Pharmaceuticals
Physical Sciences
Science & Technology
Side effects
twisted skeleton
Xenografts
CELLS
APOPTOSIS
fluorescence image
ER-STRESS
MITOCHONDRIA
MECHANISMS
chemotherapy
DELIVERY
perylene
LUNG-CANCER
molecular mechanism
IMPACT
twisted skeleton
AGENTS
PROBE
Online AccessGet full text

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Abstract The systemic use of pharmaceutical drugs for cancer patients is a compromise between desirable therapy and side effects because of the intrinsic shortage of organ‐specific pharmaceutical drug. Design and construction of pharmaceutical drug to achieve the organ‐specific delivery is thus desperately desirable. We herein regulate perylene skeleton to effect organ‐specificity and present an example of lung‐specific distribution on the basis of bay‐twisted PDIC‐NC. We further demonstrate that PDIC‐NC can target into mitochondria to act as cellular respiration inhibitor, inducing insufficient production of adenosine triphosphate, promoting endogenous H2O2 and .OH burst, elevating calcium overload, efficiently triggering the synergistic apoptosis, autophagy and endoplasmic reticulum stress of lung cancer cells. The antitumor performance of PDIC‐NC is verified on in vivo xenografted, metastasis and orthotopic lung cancer, presenting overwhelming evidences for potentially clinical application. This study contributes a proof‐of‐concept demonstration of twisted perylene to well attain lung‐specific distribution, and meanwhile achieves intensive lung cancer chemotherapy. Herein we modulate the perylene skeleton to effect organ‐specificity and present an example of lung‐specific distribution on the basis of a twisted perylene PDIC‐NC. The in vitro and in vivo biological functions of PDIC‐NC are demonstrated and its molecular mechanism for the inhibiting activity on tumour cells is revealed.
AbstractList The systemic use of pharmaceutical drugs for cancer patients is a compromise between desirable therapy and side effects because of the intrinsic shortage of organ‐specific pharmaceutical drug. Design and construction of pharmaceutical drug to achieve the organ‐specific delivery is thus desperately desirable. We herein regulate perylene skeleton to effect organ‐specificity and present an example of lung‐specific distribution on the basis of bay‐twisted PDIC‐NC. We further demonstrate that PDIC‐NC can target into mitochondria to act as cellular respiration inhibitor, inducing insufficient production of adenosine triphosphate, promoting endogenous H2O2 and .OH burst, elevating calcium overload, efficiently triggering the synergistic apoptosis, autophagy and endoplasmic reticulum stress of lung cancer cells. The antitumor performance of PDIC‐NC is verified on in vivo xenografted, metastasis and orthotopic lung cancer, presenting overwhelming evidences for potentially clinical application. This study contributes a proof‐of‐concept demonstration of twisted perylene to well attain lung‐specific distribution, and meanwhile achieves intensive lung cancer chemotherapy. Herein we modulate the perylene skeleton to effect organ‐specificity and present an example of lung‐specific distribution on the basis of a twisted perylene PDIC‐NC. The in vitro and in vivo biological functions of PDIC‐NC are demonstrated and its molecular mechanism for the inhibiting activity on tumour cells is revealed.
The systemic use of pharmaceutical drugs for cancer patients is a compromise between desirable therapy and side effects because of the intrinsic shortage of organ‐specific pharmaceutical drug. Design and construction of pharmaceutical drug to achieve the organ‐specific delivery is thus desperately desirable. We herein regulate perylene skeleton to effect organ‐specificity and present an example of lung‐specific distribution on the basis of bay‐twisted PDIC‐NC. We further demonstrate that PDIC‐NC can target into mitochondria to act as cellular respiration inhibitor, inducing insufficient production of adenosine triphosphate, promoting endogenous H 2 O 2 and . OH burst, elevating calcium overload, efficiently triggering the synergistic apoptosis, autophagy and endoplasmic reticulum stress of lung cancer cells. The antitumor performance of PDIC‐NC is verified on in vivo xenografted, metastasis and orthotopic lung cancer, presenting overwhelming evidences for potentially clinical application. This study contributes a proof‐of‐concept demonstration of twisted perylene to well attain lung‐specific distribution, and meanwhile achieves intensive lung cancer chemotherapy.
The systemic use of pharmaceutical drugs for cancer patients is a compromise between desirable therapy and side effects because of the intrinsic shortage of organ-specific pharmaceutical drug. Design and construction of pharmaceutical drug to achieve the organ-specific delivery is thus desperately desirable. We herein regulate perylene skeleton to effect organ-specificity and present an example of lung-specific distribution on the basis of bay-twisted PDIC-NC. We further demonstrate that PDIC-NC can target into mitochondria to act as cellular respiration inhibitor, inducing insufficient production of adenosine triphosphate, promoting endogenous H2 O2 and . OH burst, elevating calcium overload, efficiently triggering the synergistic apoptosis, autophagy and endoplasmic reticulum stress of lung cancer cells. The antitumor performance of PDIC-NC is verified on in vivo xenografted, metastasis and orthotopic lung cancer, presenting overwhelming evidences for potentially clinical application. This study contributes a proof-of-concept demonstration of twisted perylene to well attain lung-specific distribution, and meanwhile achieves intensive lung cancer chemotherapy.The systemic use of pharmaceutical drugs for cancer patients is a compromise between desirable therapy and side effects because of the intrinsic shortage of organ-specific pharmaceutical drug. Design and construction of pharmaceutical drug to achieve the organ-specific delivery is thus desperately desirable. We herein regulate perylene skeleton to effect organ-specificity and present an example of lung-specific distribution on the basis of bay-twisted PDIC-NC. We further demonstrate that PDIC-NC can target into mitochondria to act as cellular respiration inhibitor, inducing insufficient production of adenosine triphosphate, promoting endogenous H2 O2 and . OH burst, elevating calcium overload, efficiently triggering the synergistic apoptosis, autophagy and endoplasmic reticulum stress of lung cancer cells. The antitumor performance of PDIC-NC is verified on in vivo xenografted, metastasis and orthotopic lung cancer, presenting overwhelming evidences for potentially clinical application. This study contributes a proof-of-concept demonstration of twisted perylene to well attain lung-specific distribution, and meanwhile achieves intensive lung cancer chemotherapy.
The systemic use of pharmaceutical drugs for cancer patients is a compromise between desirable therapy and side effects because of the intrinsic shortage of organ-specific pharmaceutical drug. Design and construction of pharmaceutical drug to achieve the organ-specific delivery is thus desperately desirable. We herein regulate perylene skeleton to effect organ-specificity and present an example of lung-specific distribution on the basis of bay-twisted PDIC-NC. We further demonstrate that PDIC-NC can target into mitochondria to act as cellular respiration inhibitor, inducing insufficient production of adenosine triphosphate, promoting endogenous H2O2 and (OH)-O-. burst, elevating calcium overload, efficiently triggering the synergistic apoptosis, autophagy and endoplasmic reticulum stress of lung cancer cells. The antitumor performance of PDIC-NC is verified on in vivo xenografted, metastasis and orthotopic lung cancer, presenting overwhelming evidences for potentially clinical application. This study contributes a proof-of-concept demonstration of twisted perylene to well attain lung-specific distribution, and meanwhile achieves intensive lung cancer chemotherapy.
The systemic use of pharmaceutical drugs for cancer patients is a compromise between desirable therapy and side effects because of the intrinsic shortage of organ‐specific pharmaceutical drug. Design and construction of pharmaceutical drug to achieve the organ‐specific delivery is thus desperately desirable. We herein regulate perylene skeleton to effect organ‐specificity and present an example of lung‐specific distribution on the basis of bay‐twisted PDIC‐NC. We further demonstrate that PDIC‐NC can target into mitochondria to act as cellular respiration inhibitor, inducing insufficient production of adenosine triphosphate, promoting endogenous H2O2 and .OH burst, elevating calcium overload, efficiently triggering the synergistic apoptosis, autophagy and endoplasmic reticulum stress of lung cancer cells. The antitumor performance of PDIC‐NC is verified on in vivo xenografted, metastasis and orthotopic lung cancer, presenting overwhelming evidences for potentially clinical application. This study contributes a proof‐of‐concept demonstration of twisted perylene to well attain lung‐specific distribution, and meanwhile achieves intensive lung cancer chemotherapy.
The systemic use of pharmaceutical drugs for cancer patients is a compromise between desirable therapy and side effects because of the intrinsic shortage of organ-specific pharmaceutical drug. Design and construction of pharmaceutical drug to achieve the organ-specific delivery is thus desperately desirable. We herein regulate perylene skeleton to effect organ-specificity and present an example of lung-specific distribution on the basis of bay-twisted PDIC-NC. We further demonstrate that PDIC-NC can target into mitochondria to act as cellular respiration inhibitor, inducing insufficient production of adenosine triphosphate, promoting endogenous H O and OH burst, elevating calcium overload, efficiently triggering the synergistic apoptosis, autophagy and endoplasmic reticulum stress of lung cancer cells. The antitumor performance of PDIC-NC is verified on in vivo xenografted, metastasis and orthotopic lung cancer, presenting overwhelming evidences for potentially clinical application. This study contributes a proof-of-concept demonstration of twisted perylene to well attain lung-specific distribution, and meanwhile achieves intensive lung cancer chemotherapy.
Author Ma, Feiyan
Deng, Qingyuan
Wang, Xuejuan
Huang, Yongwei
Gao, Yijian
Qiao, Zeng‐Ying
Liu, Zhonghua
Zhu, Jianling
Chen, Qing
Xing, Xiaoyi
Lu, Feng
Wang, Hao
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  surname: Liu
  fullname: Liu, Zhonghua
  organization: Henan University
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  fullname: Chen, Qing
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  organization: Henan University
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  organization: Henan University
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  surname: Gao
  fullname: Gao, Yijian
  organization: Henan University
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  surname: Deng
  fullname: Deng, Qingyuan
  organization: Henan University
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  givenname: Zeng‐Ying
  surname: Qiao
  fullname: Qiao, Zeng‐Ying
  email: qiaozy@nanoctr.cn
  organization: University of Chinese Academy of Science (UCAS)
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  surname: Xing
  fullname: Xing, Xiaoyi
  organization: Henan University
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  surname: Zhu
  fullname: Zhu, Jianling
  organization: Henan University
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  givenname: Feng
  surname: Lu
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  email: lufeng@henu.edu.cn
  organization: Henan University
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  orcidid: 0000-0002-1961-0787
  surname: Wang
  fullname: Wang, Hao
  email: wanghao@nanoctr.cn
  organization: University of Chinese Academy of Science (UCAS)
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Keywords CELLS
APOPTOSIS
fluorescence image
ER-STRESS
MITOCHONDRIA
MECHANISMS
chemotherapy
DELIVERY
perylene
LUNG-CANCER
molecular mechanism
IMPACT
twisted skeleton
AGENTS
PROBE
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Snippet The systemic use of pharmaceutical drugs for cancer patients is a compromise between desirable therapy and side effects because of the intrinsic shortage of...
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SubjectTerms Adenosine triphosphate
Animals
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Apoptosis
Apoptosis - drug effects
ATP
Autophagy
Calcium
Cell Line, Tumor
Cell Proliferation - drug effects
Chemistry
Chemistry, Multidisciplinary
Chemotherapy
Drug development
Drug Screening Assays, Antitumor
Endoplasmic reticulum
fluorescence image
Humans
Hydrogen peroxide
Lung cancer
Lung Neoplasms - drug therapy
Lung Neoplasms - metabolism
Lung Neoplasms - pathology
Metastases
Mice
Mitochondria
molecular mechanism
perylene
Perylene - analogs & derivatives
Perylene - chemistry
Perylene - pharmacology
Phagocytosis
Pharmaceuticals
Physical Sciences
Science & Technology
Side effects
twisted skeleton
Xenografts
Title Regulating Twisted Skeleton to Construct Organ‐Specific Perylene for Intensive Cancer Chemotherapy
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