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Hydroxychloroquine: Key therapeutic advances and emerging nanotechnological landscape for cancer mitigation

Low LE 1 , Kong CK 2 , Yap WH 3 , Siva SP 4 , Gan SH 5 , Siew WS 6 Show all authors , Ming LC 7 , Lai-Foenander AS 8 , Chang SK 9 , Lee WL 10 , Wu Y 11 , Khaw KY 12 , Ong YS 13 , Tey BT 14 , Singh SK 15 , Dua K 16 , Chellappan DK 17 , Goh BH 18

Affiliations 

  • 1 Department of Chemical Engineering, School of Engineering, Monash University Malaysia, Jalan Lagoon Selatan, 47500, Bandar Sunway, Selangor Darul Ehsan, Malaysia; Advanced Engineering Platform, Monash University Malaysia, Jalan Lagoon Selatan, 47500, Bandar Sunway, Selangor Darul Ehsan, Malaysia; Monash-Industry Plant Oils Research Laboratory (MIPO), Monash University Malaysia, Jalan Lagoon Selatan, 47500, Bandar Sunway, Selangor Darul Ehsan, Malaysia. Electronic address: low.liangee@monash.edu
  • 2 Biofunctional Molecule Exploratory (BMEX) Research Group, School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, 47500, Bandar Sunway, Selangor Darul Ehsan, Malaysia; Department of Primary Care Medicine, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia. Electronic address: cheekei92@gmail.com
  • 3 School of Biosciences, Taylor's University, 47500, Subang Jaya, Selangor Darul Ehsan, Malaysia; Centre for Drug Discovery and Molecular Pharmacology, Faculty of Medical and Health Sciences, Taylor's University, Subang Jaya 47500, Malaysia. Electronic address: weihsum.yap@taylors.edu.my
  • 4 Biofunctional Molecule Exploratory (BMEX) Research Group, School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, 47500, Bandar Sunway, Selangor Darul Ehsan, Malaysia. Electronic address: gee9324@gmail.com
  • 5 Biofunctional Molecule Exploratory (BMEX) Research Group, School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, 47500, Bandar Sunway, Selangor Darul Ehsan, Malaysia. Electronic address: gan.siewhua@monash.edu
  • 6 School of Biosciences, Taylor's University, 47500, Subang Jaya, Selangor Darul Ehsan, Malaysia. Electronic address: vin.siew@gmail.com
  • 7 Department of Medical Sciences, School of Medical and Life Sciences, Sunway University, Sunway City, Selangor, Malaysia. Electronic address: longchiauming@gmail.com
  • 8 Biofunctional Molecule Exploratory (BMEX) Research Group, School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, 47500, Bandar Sunway, Selangor Darul Ehsan, Malaysia. Electronic address: ashfoe98@gmail.com
  • 9 Department of Allied Health Sciences, Faculty of Science, Universiti Tunku Abdul Rahman, Kampar, 31900, Perak, Malaysia. Electronic address: changsk@utar.edu.my
  • 10 School of Science, Monash University Malaysia, Jalan Lagoon Selatan, 47500, Bandar Sunway, Selangor Darul Ehsan, Malaysia. Electronic address: lee.wai.leng@monash.edu
  • 11 College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang, 310058, PR China. Electronic address: yjwu@zju.edu.cn
  • 12 Biofunctional Molecule Exploratory (BMEX) Research Group, School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, 47500, Bandar Sunway, Selangor Darul Ehsan, Malaysia. Electronic address: khaw.kooiyeong@monash.edu
  • 13 Biofunctional Molecule Exploratory (BMEX) Research Group, School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, 47500, Bandar Sunway, Selangor Darul Ehsan, Malaysia. Electronic address: ong.yongsze@monash.edu
  • 14 Department of Chemical Engineering, School of Engineering, Monash University Malaysia, Jalan Lagoon Selatan, 47500, Bandar Sunway, Selangor Darul Ehsan, Malaysia; Advanced Engineering Platform, Monash University Malaysia, Jalan Lagoon Selatan, 47500, Bandar Sunway, Selangor Darul Ehsan, Malaysia. Electronic address: tey.beng.ti@monash.edu
  • 15 School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar-Delhi G.T Road, Phagwara, Punjab, India; Australian Research Centre in Complementary and Integrative Medicine, Faculty of Health, University of Technology Sydney, Ultimo, NSW, 2007, Australia. Electronic address: sachin.16030@lpu.co.in
  • 16 Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo, NSW, 2007, Australia; Australian Research Centre in Complementary and Integrative Medicine, Faculty of Health, University of Technology Sydney, Ultimo, NSW, 2007, Australia; Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun 248007, Uttarakhand, India. Electronic address: kamal.dua@uts.edu.au
  • 17 Department of Life Sciences, School of Pharmacy, International Medical University (IMU), 57000 Bukit Jalil, Kuala Lumpur, Malaysia. Electronic address: dinesh_kumar@imu.edu.my
  • 18 Biofunctional Molecule Exploratory (BMEX) Research Group, School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, 47500, Bandar Sunway, Selangor Darul Ehsan, Malaysia; College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang, 310058, PR China; Sunway Biofunctional Molecules Discovery Centre (SBMDC), School of Medical and Life Sciences, Sunway University, Sunway City, Selangor, Malaysia. Electronic address: goh.bey.hing@monash.edu
Chem Biol Interact, 2023 Dec 01;386:110750.
PMID: 37839513 DOI: 10.1016/j.cbi.2023.110750

Abstract

Hydroxychloroquine (HCQ) is a unique class of medications that has been widely utilized for the treatment of cancer. HCQ plays a dichotomous role by inhibiting autophagy induced by the tumor microenvironment (TME). Preclinical studies support the use of HCQ for anti-cancer therapy, especially in combination with conventional anti-cancer treatments since they sensitize tumor cells to drugs, potentiating the therapeutic activity. However, clinical evidence has suggested poor outcomes for HCQ due to various obstacles, including non-specific distribution, low aqueous solubility and low bioavailability at target sites, transport across tissue barriers, and retinal toxicity. These issues are addressable via the integration of HCQ with nanotechnology to produce HCQ-conjugated nanomedicines. This review aims to discuss the pharmacodynamic, pharmacokinetic and antitumor properties of HCQ. Furthermore, the antitumor performance of the nanoformulated HCQ is also reviewed thoroughly, aiming to serve as a guide for the HCQ-based enhanced treatment of cancers. The nanoencapsulation or nanoconjugation of HCQ with nanoassemblies appears to be a promising method for reducing the toxicity and improving the antitumor efficacy of HCQ.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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