Contents lists available at ScienceDirect Reactive and Functional Polymers journal homepage: www.elsevier.com/locate/react Perspective Article Vincristine-loaded polymeric corona around gold nanorods for combination (chemo-photothermal) therapy of oral squamous carcinoma Wael M. Darwish a, ⁎ , Ahmed S. Abdoon b , Mona S. Shata c , Merhan Elmansy c a Laser Technology Group, Center of Excellence for Advanced Sciences and Department of Polymers and Pigments, National Research Centre, El Buhouth Street, Dokki, 12622 Cairo, Egypt b Animal Reproduction Department, Veterinary Research Division, National Research Centre, El Buhouth Street, Dokki, 12622 Cairo, Egypt c Department of Oral Pathology, Faculty of Dentistry, Suez Canal University, Ismailia, Egypt ARTICLE INFO Keywords: Polymer corona Gold nanorods Vincristine Combination therapy Oral squamous carcinoma ABSTRACT In this work, we describe the design of a novel combination (chemo-photothermal) therapeutic model com- prising vincristine (VCR) as phytochemical anticancer and plasmonic gold nanorods (GNRs) for laser-induced photothermal ablation of tumor. VCR was loaded in an amphiphilic PLGA-PEG polymeric corona covalently assembled around silica coated GNRs. The acid sensitive amide linkage conferred a VCR sustained release profile in the cancer acidic microenvironment. In vitro studies showed the high stability of the multilayer nanoprobes in the physiological medium (pH 7.4) versus a sustained release profile of VCR in stimulated cancer micro- environment (pH = 5.0). Treatment of golden hamster with chemically-induced oral squamous carcinoma (OSCC) with the proposed nanoformulations revealed superior anticancer efficacy in terms of reduced mortality rates, tumor regression and dramatic histopathological changes of the cancer cells within the therapeutic course. 1. Introduction Combination therapy has been recently proposed to overcome the heterogeneity of cancer and the increasing number of multi-drug re- sistive cancer cells [1,2]. Combined therapy of two or more drugs promotes synergism among the different drugs against cancer cells and suppresses drug resistance through distinct mechanisms of action [3]. Plasmonic photothermal therapy (PPTT), a process involving adminis- tration of gold nanorods (GNRS) and a subsequent eradication with near infrared (NIR) laser, has shown a high potential for treatment of many cancer types [4]. GNRs/polypyrrole/silica core/shell nano- composites were utilized as drug nanocarriers for efficient chemo- photothermal therapy [5]. Similarly, GNRs with a non-covalently tai- lorable surface were used for image-guided chemo-photothermal cancer therapy [6]. El-Sayed et al. [7] reported on a superior tumor regression in squamous cell carcinoma (SCC). Vincristine (VCR), a vinca antic- ancer alkaloid obtained from the periwinkle plant, acts as anti- microtubule agents that blocks mitosis by arresting cells in the meta- phase [8]. VCR proved superior efficiency for treatment of squamous cell carcinoma in a puma (Puma concolor)[9]. Many studies have been done to verify the efficacy, safety, doses and pharmacokinetics of VCR intraperitoneal administration [10]. Despite intralesional VCR injection showed high in vitro therapeutic efficiency against oral squamous carcinoma (OSCC) [2], systemic administration of VCR causes many side effects. Therefore, several attempts have been carried out to en- hance the in-vivo delivery of vincristine. Poly(DL-lactide-co-glycolide) (PLGA) is a biocompatible/biodegradable polymer recently approved by FDA for use human therapy [11]. In vivo degradation products of PLGA are easily metabolized in the body via the Krebs cycle and eliminated as carbon dioxide and water [12]. In addition, poly(ethylene glycol) (PEG) to PLGA provides nanocapsules of significantly reduced reticuloendothelial (RES) uptake and prolonged blood circulating time [7]. In this work, we describe a novel design of combination (chemo- photothermal) therapy comprising (VCR) as phytochemical anticancer and plasmonic gold nanorods (GNRs) as photothermal reagent. To verify the anticancer effect of the prepared nano corona on late stage oral squamous cell carcinoma (OSCC), formulations were in- traperitoneal (IP) administrated to golden hamster with chemically induced OSCC. Mortality rates, tumor size and cell morphological changes were monitored within the therapeutic course. Finally, the results were rationalized to the characteristics of the proposed design. 2. Experimental Approval of Research Ethics Committee, Faculty of Dentistry, Suez Canal University was obtained before starting this work. https://doi.org/10.1016/j.reactfunctpolym.2020.104575 Received 8 February 2020; Received in revised form 20 March 2020; Accepted 22 March 2020 ⁎ Corresponding author. E-mail address: wmdarwish55@gmail.com (W.M. Darwish). Reactive and Functional Polymers 151 (2020) 104575 Available online 23 March 2020 1381-5148/ © 2020 Elsevier B.V. All rights reserved. T