Targeted and stimuli-responsive mesoporous silica nanoparticles for drug delivery and theranostic use Md Aquib 1 , Muhammad Asim Farooq 1 , Parikshit Banerjee 2 , Fahad Akhtar 3 , Mensura Sied Filli 1 , Kofi Oti Boakye-Yiadom 1 , Samuel Kesse 1 , Faisal Raza 1 , Mily Bazezy Joelle Maviah 1 , Rukhshona Mavlyanova 1 , Bo Wang 1 * 1 Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 211198, P R China. 2 Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 211198, P R China 3 School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu 211198, P R China. *Corresponding author: Bo Wang (Telephone: +86-13913990858; Fax: +86-25- 86185328; E-mail: bwangcpu2000@gmail.com) Abstract For cancer therapy, the usefulness of mesoporous silica nanoparticles (MPSNPs) has been widely discussed, likely due to its inorganic nature and excellent structural features. The MPSNPs-based chemotherapeutics have been promisingly delivered to their target sites that help to minimize side effects and improve therapeutic effectiveness. A wide array of studies have been conducted to functionalize drug-loaded MPSNPs using targeting ligands and stimuli-sensitive substances. In addition, anticancer drugs have been precisely delivered to their target sites using MPSNPs, which respond to multi-stimuli. Furthermore, MPSNPs have been extensively tested for their safety and compatibility. The toxicity level of MPSNPs is substantially lower as compared to that of colloidal silica; however, in oxidative stress, they exhibit cytotoxic features. The biocompatibility of MPSNPs can be improved by modifying their surfaces. This article describes the production procedures, functionalization, and applications of biocompatible MPSNPs in drug delivery. Keywords: Mesoporous silica nanoparticles, chemotherapeutics, functionalization, biocompatibility, cytotoxicity. 1. Introduction Cancer is a lethal disease that is characterized by an unrestrained buildup of abnormal cells. Untreated cancer spreads to various internal organs and thus is responsible for the highest occurrence of deaths worldwide [1, 2] that could be attributed to different social (such as inactive lifestyle), economic (such as poverty), and environmental factors (such as pollution) in various areas [3]. In recent years, the researchers have gained several achievements in cancer treatment. In the course of cancer eradication, there are still several challenges such as the affected site or organ in the body, risk of damage to non-diseased cells, and drug access to cancer cells [4]. For instance, the treatment of brain cancer is comparatively difficult due to its vulnerable site and the challenge of crossing the blood-brain barrier to deliver drugs to the brain [4]. In This article is protected by copyright. All rights reserved. Accepted Article This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/jbm.a.36770