International Journal of Biological Macromolecules 70 (2014) 572–582 Contents lists available at ScienceDirect International Journal of Biological Macromolecules j ourna l ho me pa g e: www.elsevier.com/locate/ijbiomac Carboplatin loaded protein nanoparticles exhibit improve anti-proliferative activity in retinoblastoma cells Farhan Ahmed a , Mohammad Javed Ali b , Anand K. Kondapi a,∗ a Department Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, India b L.V. Prasad Eye Institute, Hyderabad, India a r t i c l e i n f o Article history: Received 24 September 2013 Received in revised form 22 July 2014 Accepted 23 July 2014 Available online 1 August 2014 Keywords: Protein nanoparticle Carboplatin Retinoblastoma a b s t r a c t Retinoblastoma, a common neoplasm of eye in children accounts about 9–10% of all paediatric cancer. Carboplatin (carbo) is preferred chemotherapeutic regimen. In this study the prospective of carbo- platin loaded apotranferrin (Apo-nano-carbo) and lactoferrin (Lacto-nano-carbo) nanoparticles have been demonstrated for the treatment of retinoblastoma. Apo-nano-carbo and Lacto-nano-carbo were prepared by sol-oil method (as a patented formula) with size of 82–92 nm and 68–81 nm, hydrodynamic size were 142 ± 15 nm and 263 ± 20 nm, encapsulation efficiency were 50% ± 2.3 and 52% ± 3.9 respec- tively. Results of pH dependent-drug release and receptor-blocking assay showed that nanoparticles may deliver drug through receptor mediated endocytosis. The carboplatin loaded nanoparticles shows greater intracellular uptake, sustained retention and thus, high anti-proliferative activity (Apo-nano- carbo IC 50 = 4.31 g ml -1 , Lacto-nano-carbo IC 50 = 4.16 g ml -1 , Sol-carbo IC 50 = 13.498 g ml -1 ) into the retinoblastoma cells compared to their soluble counterpart. © 2014 Elsevier B.V. All rights reserved. 1. Introduction Retinoblastoma (RB) is the most common intraocular tumour in children, affecting 1:15,000 live births per annum [1,2]. The sur- vival rate of retinoblastoma in developing countries is decreased substantially compared to the developed countries. One of the main reasons which account for this poor survival rate is delayed diagno- sis because of lower socio-economic status, meagre education and inadequate healthcare system [3]. Retinoblastoma is caused by mutation in both alleles of the retinoblastoma tumour suppressor gene (rb1). As a consequence of the mutation in this gene, it leads to induction of the pro- liferative pathway, which causes a plethora of malignancies [4]. Treatment of retinoblastoma had been limited to enucleation [5] but most recently, procedures such as external radiation beam ther- apy (ERBT), episcleral plaque radiotherapy (EPR) and focal therapy are being routinely used to treat RB [6]. However, these procedures are often accompanied with side effects such as cataract, radia- tion retinopathy, incidence of secondary malignant neoplasms and facial deformities [7]. Recent therapy of RB management involves ∗ Corresponding author at: Department of Biotechnology, School of Life Sciences, University of Hyderabad, Hyderabad-500046, India. Tel.: +91 40 23134571(O), +91 40 23000654(R), +91 9246212654(M); fax: +91 40 23010145. E-mail addresses: akksl@uohyd.ernet.in, akondapi@gmail.com (A.K. Kondapi). systemic platinum based chemotherapy in conjunction with focal therapy [8]. Platinum based anticancer therapy involves the use of Carboplatin. Carboplatin is an anticancer drug, universally used for the treatment of retinoblastoma. However, this therapy too is associated with numbers of life threating side effects such as neu- tropenia, thrombocytopenia, renal toxicity and hepatotoxicity [9]. In addition to this the clinical scope of this therapy is limited due to systemic toxicity, rapid blood clearance and resistance to cancerous cells [10]. Drug delivery in eye remains a challenge for the physicians because it is protected from various defensive barriers. Intense research efforts are being carried out to develop and improve method for drug delivery into the eye. Amongst the methods are being developed, nanoparticle is one of them. The method of drug delivery by nanoparticles formulation has also been found to be promising to overcome the above limitations. Nanoparticles are submicron particle that can encapsulate the therapeutic molecule in order to reduce the problem associated with drug delivery, like penetration across the blood-retina barrier and retention time in blood circulation. They are polymeric colloidal particles with diam- eters oscillating from 10 to 1000 nm, in which the therapeutic molecule of interest can be loaded within the polymeric matrix or adsorbed or conjugated on the surface [11]. Biodegradable polymeric nanoparticles, a form of NP, have gained considerable research interest in recent years because of their compatibility with the various tissues of the body, including http://dx.doi.org/10.1016/j.ijbiomac.2014.07.041 0141-8130/© 2014 Elsevier B.V. All rights reserved.