PMID- 37179196
OWN - NLM
STAT- MEDLINE
DCOM- 20230526
LR  - 20230526
IS  - 1095-7103 (Electronic)
IS  - 0021-9797 (Linking)
VI  - 645
DP  - 2023 Sep
TI  - Autophagy-induced intracellular signaling fractional nano-drug system for 
      synergistic anti-tumor therapy.
PG  - 986-996
LID - S0021-9797(23)00816-0 [pii]
LID - 10.1016/j.jcis.2023.05.031 [doi]
AB  - Autophagy inducers increase the sensitivity of tumor cells to chemotherapeutic 
      drugs and enhance anti-tumor efficacy. An autophagy-induced intracellular 
      signaling fractional nano-drug system was constructed for the co-delivery of the 
      autophagy inducer rapamycin (RAPA) and the anti-tumor drug 
      9-nitro-20(S)-camptothecin (9-NC). Link peptides, including cathepsin B-sensitive 
      peptides (Ala-Leu-Ala-Leu, ALAL), nucleus-targeting peptides (TAT, sequence: 
      YGRKKRRQRRR), and chrysin (CHR)-modified hydrophobic biodegradable polymers 
      (poly(-caprolactone)) (PCL), were grafted onto hyaluronic acid (HA) to yield two 
      amphiphiles, HA-ALAL-PCL-CHR (CPAH) and HA-ALAL-TAT-PCL-CHR (CPTAH). Spherical 
      RAPA- and 9-NC-loaded micelles were obtained by the self-assembly of amphiphiles 
      comprising CPAH and RAPA and CPTAH and 9-NC. In this fractional nano-drug system, 
      RAPA was released earlier than 9-NC, as CPAH as a RAPA carrier lacked a 
      nucleus-targeting TAT (unlike CPTAH as an 9-NC carrier). RAPA induced autophagy 
      in tumor cells and improved their sensitivity, whereas the secondary 
      nucleus-targeting micelles directly delivered 9-NC to the nucleus, considerably 
      improving anti-tumor efficacy. Immunofluorescence staining, acridine orange (AO) 
      staining, and western blotting results demonstrated that the system induced a 
      high level of autophagy in combination chemotherapy. The proposed system 
      possesses a high level of cytotoxicity in vitro and in vivo and provides a 
      potential method for enhancing anti-tumor efficacy in clinical settings.
CI  - Copyright (c) 2023 Elsevier Inc. All rights reserved.
FAU - Yan, Jianqin
AU  - Yan J
AD  - Department of Pharmaceutics, School of Pharmacy, Qingdao University, Qingdao 
      266073, China.
FAU - Shan, Chan
AU  - Shan C
AD  - Institute of Translational Medicine, The Affiliated Hospital of Qingdao 
      University, College of Medicine, Qingdao University, Qingdao 266021, China.
FAU - Zhang, Zhuoran
AU  - Zhang Z
AD  - Department of Dentistry, Qingdao Special Service Sanatorium of PLA Navy, Qingdao 
      266021, China.
FAU - Li, Fashun
AU  - Li F
AD  - Department of Pharmaceutics, School of Pharmacy, Qingdao University, Qingdao 
      266073, China.
FAU - Sun, Yong
AU  - Sun Y
AD  - Department of Pharmaceutics, School of Pharmacy, Qingdao University, Qingdao 
      266073, China. Electronic address: sunyong@qdu.edu.cn.
FAU - Wang, Qian
AU  - Wang Q
AD  - Department of Pharmaceutics, School of Pharmacy, Qingdao University, Qingdao 
      266073, China.
FAU - He, Bin
AU  - He B
AD  - National Engineering Research Center for Biomaterials, Sichuan University, 
      Chengdu 610064, China.
FAU - Luo, Kui
AU  - Luo K
AD  - Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital, 
      Sichuan University, Chengdu 610041, China.
FAU - Chang, Jing
AU  - Chang J
AD  - College of Marine Life Science, Ocean University of China, Qingdao 266003, China.
FAU - Liang, Yan
AU  - Liang Y
AD  - Department of Pharmaceutics, School of Pharmacy, Qingdao University, Qingdao 
      266073, China. Electronic address: Liangyan072@foxmail.com.
LA  - eng
PT  - Journal Article
DEP - 20230509
PL  - United States
TA  - J Colloid Interface Sci
JT  - Journal of colloid and interface science
JID - 0043125
RN  - 0 (Micelles)
RN  - 0 (Antineoplastic Agents)
RN  - W36ZG6FT64 (Sirolimus)
RN  - 0 (Drug Carriers)
RN  - 0 (Peptides)
SB  - IM
MH  - Humans
MH  - Micelles
MH  - *Antineoplastic Agents/chemistry
MH  - Sirolimus/pharmacology/therapeutic use
MH  - *Neoplasms/drug therapy/pathology
MH  - Drug Carriers/chemistry
MH  - Peptides/pharmacology
MH  - *Nanoparticles/therapeutic use
MH  - Autophagy
MH  - Cell Line, Tumor
OTO - NOTNLM
OT  - 9-nitro-20(S)-camptothecin/rapamycin co-delivery
OT  - Autophagy
OT  - Graded release
OT  - Synergistic therapy
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/05/14 01:07
MHDA- 2023/05/26 06:42
CRDT- 2023/05/13 22:00
PHST- 2023/02/27 00:00 [received]
PHST- 2023/05/04 00:00 [revised]
PHST- 2023/05/05 00:00 [accepted]
PHST- 2023/05/26 06:42 [medline]
PHST- 2023/05/14 01:07 [pubmed]
PHST- 2023/05/13 22:00 [entrez]
AID - S0021-9797(23)00816-0 [pii]
AID - 10.1016/j.jcis.2023.05.031 [doi]
PST - ppublish
SO  - J Colloid Interface Sci. 2023 Sep;645:986-996. doi: 10.1016/j.jcis.2023.05.031. 
      Epub 2023 May 9.