25322-68-3 Contents lists available at ScienceDirect br
Contents lists available at ScienceDirect
Colloids and Surfaces B: Biointerfaces
journal homepage: www.elsevier.com/locate/colsurfb
Cancer cell membrane-cloaked mesoporous silica nanoparticles with a pH- T sensitive gatekeeper for cancer treatment
Chang-Ming Liu1, Guang-Bing Chen ,1, Hui-Hong Chen, Jia-Bin Zhang, Hui-Zhang Li, Ming-Xiong Sheng, Wu-Bin Weng, Shan-Ming Guo
Department of Urology, Mindong Hospital Aﬃliated to Fujian Medical University, Fu’an, 355000, People’s Republic of China
Cancer cell membrane
Mesoporous silica nanoparticle
Nanoparticular drug delivery system (NDDS) has great potential for enhancing the eﬃcacy of traditional che-motherapeutic drugs. However, it is still a great challenge to fabricate a biocompatible NDDS with simple structure capable of optimizing therapeutic eﬃcacy, such as high tumor accumulation, suitable drug release profile (e.g. no premature drug leakage in normal physiological conditions while having a rapid release in cancer cells), low immunogenicity, as well as good biocompatibility. In this work, a simple core/shell structured na-noparticle was fabricated for prostate cancer treatment, in which a mesoporous silica nanoparticle core was applied as a container to high-eﬃciently encapsulate drugs (doxorubicin, DOX), CaCO3 interlayer was designed to act as sheddable pH-sensitive gatekeepers for controlling drug release, and cancer cell membrane wrapped outlayer could improve the colloid stability and tumor accumulation capacity. In vitro cell experiments de-monstrated that the as-prepared nanovehicles (denoted as DOX/[email protected]@CM) could be eﬃciently uptaken by LNCaP-AI prostate cancer 25322-68-3 and even exhibited a better anti-tumor eﬃciency than free DOX. In addition, Live/Dead cell detection and apoptosis experiment demonstrated that MSN/[email protected]@CM could eﬀectively induce apoptosis-related death in prostate cancer cells. In vivo antitumor results demonstrated that DOX/ [email protected]@CM administration could remarkably suppress the tumor growth. Compared with other tedious approaches to optimize the therapeutic eﬃcacy, this study provides an eﬀective drug targeting system only using naturally biomaterials for the treatment of prostate cancer, which might have great potential in clinic usage. r> 1. Introduction
Doxorubicin (DOX) is a common chemotherapeutic drug that has a broad spectrum of antitumor activity, including acute lymphoblastic leukemia, granulocytic leukemia, breast cancer, lung cancer, and bladder cancer [1–3]. The antitumor mechanism of DOX is to bind DNA and hinder the replication of DNA, thereby inhibiting cell cycle of tu-mors . However, the application of DOX also causes some obvious side eﬀects, including impaired bone marrow hematopoietic function, cardiotoxicity, nausea, hair loss, high fever and so on . Therefore, it is very important to develop an appropriate drug delivery system for controlling DOX at the tumor site which can reduce their side eﬀects.
Nanomaterial-based drug delivery systems have played important roles in the treatment of tumors in recent years [6–9]. Mesoporous si-lica nanoparticles (MSNs) are a kind of very promising nanomaterials as drug delivery vehicles due to good bio-safety, high drug loading capa-city, uniform size distribution, convenient synthesis and easily tunable
E-mail address: [email protected] (G.-B. Chen). 1 These authors contributed equally to this work.
pore size and pore structure [10–12]. More importantly, the MSNs surface can be modified to adhere various types of “gate-keeper” on the pore entrance to control drug release. These gate-keepers include polymers [13,14], cyclodextrin , inorganic nanoparticles , and bio-macromolecules  which are developed for the eﬃciently cap-ping of the outlets of pore. The gatekeepers are opened only in the presence of specific internal or external stimuli, thus achieving “zero premature release’’ before reaching the targeted cancer cells, which abate the harm to the normal cells [18,19]. Even so, most of the present MSNs incorporating with gatekeepers still suﬀer from tedious compo-sition, complicated fabrication, and high cost. Moreover, the gate-keeper itself is none-degradable or even degradable but bring out un-desirable toxic product, which makes this nanosystem diﬃcult to use in clinic . Therefore, it is urgent to create MSNs-based drug delivery system (DDS) that can be synthesized by a facile route, with low cost, simple structure, high compatibility, and high potency.